Therapeutic treatment methods

This application is a continuation and claims priority under 35 USC § 120 of U.S. application Ser. No. 10/728,400 filed Dec. 5, 2003 now abandoned which is a continuation-in-part of U.S. application Ser. No. 10/651,515, filed Aug. 28, 2003, now abandoned which claims benefit under 35 USC § 119(e) of abandoned U.S. provisional application Ser. No. 60/407,146, filed Aug. 28, 2002, abandoned U.S. provisional application Ser. No. 60/408,332, filed Sep. 4, 2002, and abandoned U.S. provisional application Ser. No. 60/479,257, filed Jun. 17, 2003, all of which are incorporated herein by reference.

The invention relates to methods to use compounds, such as 3β-hydroxy-16α-fluoro-17β-aminoandrost-5-ene, 3β-hydroxy-16β-fluoro-17β-aminoandrost-5-ene, 3β-hydroxy-17β-aminoandrost-5-ene, 1α,3β-dihydroxy-4α-fluoroandrost-5-ene, 1α,3β,17β-trihydroxy-4α-fluoroandrost-5-ene, 1β,3β-dihydroxy-6-bromoandrost-5-ene-17-one, 1α-fluoro-3β,12α-dihydroxyandrost-5-ene-17-one, 1α-fluoro-3β,4α-dihydroxyandrost-5-ene and 4α-fluoro-3β,6α,17β-trihydroxyandrostane to treat, ameliorate or prevent neutropenia, cystic fibrosis conditions or other pathological or disease conditions or their symptoms.

Immune dysregulation can be a component of many pathological diseases or conditions. Such dysregulation may be a factor that favors the establishment, maintenance or progression of these diseases or conditions. Deficient immune responses or immune suppression can enhance a mammal's susceptibility to infection or to the development of cancer. Conversely, excessive or inappropriate immune responses can play a role in the establishment or progression of unwanted inflammation or autoimmune conditions. It would thus be advantageous to utilize agents that can modulate immune responses and to at least partially reverse immune dysregulation when such dysregulation is a component of a given pathological condition. Some agents are known that can ameliorate some aspects of immune dysregulation, but typically such agents have their own unwanted effects on either the host's immune system or other organs or tissues. Agents such as glucocorticoid steroids have been used to reduce unwanted inflammation in a number of clinical conditions, but such compounds often have serious limitations, such as inducing immune suppression or causing unwanted mood changes.

Human and mammalian immune responses to infections or other conditions are often characterized by responses mediated by different immune effector cell populations. In some situations, helper T cells designated Th1 in the murine system, facilitate immune effector functions that are typically dominated by cell-mediated responses. In other cases, helper T cells designated Th2 cells facilitate immune effector functions that are typically dominated by humoral responses. A vigorous Th1 response is usually desirable to help clear infections or to slow the progression of an infection. When a subject's immune response is biased to, or dominated by, a Th2-type response, the cytokines associated with the Th2 response tend to suppress the immune system's capacity to mount a vigorous Th1 response at the same time. The converse is also generally true. When mammalian immune responses begin to result in an increasing Th1 response, Th2 responses tend to weaken. Insufficient Th1 responses may be associated with progression of some infections or other conditions, see, e.g., M. Clerici and G. M. Shearer, Immunol. Today 14:107-111, 1993; M. Clerici and G. M. Shearer, Immunol. Today 15:575-581, 1994.

Methods to make and use 3β-hydroxyandrost-5-ene-17-one (dehydroepiandrosterone) and certain other steroids and their biological properties have been described, see, e.g., U.S. Pat. Nos. 2,833,793, 2,911,418, 3,148,198, 3,471,480, 3,976,691, 4,000,125, 4,083,969, 4,268,441, 4,427,649, 4,542,129, 4,666,898, 4,956,355, 5,001,119, 5,043,165, 5,077,284, 5,028,631, 5,110,810, 5,157,031, 5,162,198, 5,175,154, 5,277,907, 5,292,730, 5,296,481, 5,372,996, 5,387,583, 5,407,684, 5,424,463, 5,461,042, 5,478,566, 5,506,223, 5,518,725, 5,527,788, 5,527,789, 5,532,230, 5,559,107, 5,562,910, 5,583,126, 5,585,371, 5,587,369, 5,591,736, 5,593,981, 5,629,295, 5,610,150, 5,635,496, 5,641,766, 5,641,768, 5,656,621, 5,660,835, 5,686,438, 5,696,106, 5,700,793, 5,707,983, 5,709,878, 5,710,143, 5,714,481, 5,728,688, 5,736,537, 5,744,462, 5,753,237, 5,756,482, 5,776,921, 5,776,923, 5,780,460, 5,795,880, 5,798,347, 5,798,348, 5,804,576, 5,807,848, 5,807,849, 5,811,418, 5,824,313, 5,824,668, 5,824,671, 5,827,841, 5,837,269, 5,837,700, 5,843,932, 5,846,963, 5,859,000, 5,872,114, 5,872,147, 5,162,198, 5,206,008, 5,292,730, 5,407,684, 5,461,042, 5,461,768, 5,478,566, 5,585,371, 5,635,496, 5,641,766, 5,837,269, 5,885,977, 5,846,963, 5,919,465, 5,869,090, 5,863,910, 5,856,340, 5,804,576, 5,714,481, 6,150,336, 4,978,532, 4,898,694, 4,542,129, 3,711,606, 3,710,795, 3,189,597, 3,137,710 and 2,531,441; German patent numbers 2,035,738 and 2,705,917; PCT publication numbers WO 95/21617, WO 97/38695, WO 97/48367, WO 98/05338, WO 98/50040, WO 98/50041, WO 98/58650, WO 00/32176, WO 00/32177, WO 00/32201, WO 00/35472, WO 00/56757, WO 01/30802, WO 93/20696, WO 99/25333, WO 01/30802, WO 01/23405, WO 02/28880, WO 02/69977 and WO 03/039554; European publication numbers 0020029, 0090736, 0133995, 0934745 and 0637203; E. R. Glazier, J. Org. Chem. 1962 27:2937-2938, Ben-David, et al., Proc. Soc. Expt. Biol. Med. 1967 125:1136-1140, Coleman et al., Diabetes 1982 31:830, Oertel, et al., J. Steroid Biochem. 1972 3:493-496, Pashko, et al., Carcinogenesis 1981 2:717-721, Schwartz et al., Nutr. Cancer 1981 3:46-53, Dyner et al., J. Acquired Immune Deficiency Syndromes 1993 6:459-465, M. H. Whitnall et al., Int'l. J. Immunopharmacology 2000 22:1-14, I. Porsova-Dutoit et al., Physiological Res. 2000 49 (Suppl. 1):S43-S56, R. L. Jesse et al., Ann. N.Y. Acad. Sci. 1995 774:281-290, C. Chavis et al., Steroids 1982 39:129-147, M. Numazawa and Y. Osawa Steroids 1981 38:149-159, G. Flouret et al., J. Med. Chem. 1972 15:1281-1283 and A. A. Afanasii and Y. A. Titov, Total Steroid Synthesis , Plenum Press, New York, 1970, see, e.g., p 1-304.

U.S. Pat. Nos. 4,908,358 and 4,902,681 describe the capacity of compounds such as 5α-pregnan-3,20-dione, cortexolone, 17-hydroxyprogesterone and 16α-methylprogesterone to inhibit the clearance of antibody-coated cells from circulation in disorders such as immune thrombocytopenic purpura or immune hemolytic anemia.

U.S. Pat. Nos. 5,532,230, 5,686,438, 5,753,640 and 5,811,418 and J. Bratt and M. Heimburger, Scand. J. Rheumatol. 1999 28:308-313 describe the capacity of compounds such as prednisolone, and 3β-hydroxyandrost-5-ene-17-one to limit tissue damage in ischemic tissues by inhibiting adhesion of cells such as neutrophils to endothelial cells or to treat pulmonary hypertension.

U.S. Pat. No. 5,859,000 describes the capacity compounds such as 3β-hydroxyandrost-5-ene-17-one to reduce mast cell mediated allergic reactions.

U.S. Pat. Nos. 5,763,433 and 6,372,732 and PCT publication WO 96/35428 describe the capacity of certain androstane and androstene compounds such as 3β-hydroxyandrost-5-ene-17-one to treat certain immune disorder conditions such as systemic lupus erythematosus.

U.S. Pat. Nos. 5,925,630, 5,939,545 and 5,962,443 describe the capacity of 19-nur-pregnane steroids, 3α-hydroxy-5α-pregnan-20-one and related steroids to modulate certain neurological activities such as hypothalamic function and GABA receptor activity.

Other biological effects and/or metabolic conversions of steroid compounds have been described, e.g., Batta et al., J. Biol. Chem. 1986 25:127-133, Belli et al., Liver 1991 11:162-169, Bhattacharjee et al., Anal. Biochem. 1992 201:233-236, Blake et al., Int. J. Peptide Protein Res. 1982 20:97-101, 1986 25:127-133, Bonaventura, Am. J. Obstet. Gynecol. 1978 131:403-409, Bucala et al., J. Steroid Biochem. 1986 25:127-133, Carey et al., Biochem. 1981 20:3637-3648, Chen et al., Carcinogenesis 1999 20:249-254, Chen et al., Carcinogenesis 1998 19:2187-2193, Chow et al., Antisense Res. Dev. 1994 4:81-86, Citro et al., Dis. Colon Rectum 1994 37(2 Suppl):S127-S132, Cleary, Proc. Soc. Exp. Biol. Med. 1991 196:8-16, Cleary, Int. J. Biochem. 1990 22:205-210, Crawford et al., Lab. Invest. 1994 71:42-51, Danenberg et al., Antimicrob. Agents Chemother. 1992 36:2275-2279, Dotzlaw et al., Cancer Res. 1999 59:529-532, Falany et al., J. Steroid Biochem. Mol. Biol. 1994 48:369-375, Faredin et al., J. Investigative Dermatol. 1969 52:357-361, Galigniana et al., Mol. Pharmacol. 1999 55:317-323, Goto et al., J. Chromatogr. 1983 276:289-300, Grenot Biochem. 1992 31:7609-7621, Hofbauer et al., Life Sci. 1999 64:671-679, Huijghebaert et al., J. Lipid Res. 1986 27:742-752, Hurd et al., Oncogene 1999 18:1067-1072, Iida et al., J. Lipid Res. 1995 36:628-638, Jellinck et al., Steroids 1967 10:329-346, Jonsson et al., J. Pediatr. Gastroenterol. Nutr. 1995 20:394-402, Kalimi et al, Mol. Cell. Biochem. 1994 131:99-108, Kramer et al., J. Biol. Chem. 1994 269:10621-10627, LaRochelle et al., Steroids 1984 43: 209-217, Liao et al., Carcinogenesis 1998 19:2173-2180, Lillienau et al., J. Clin. Invest. 1992 89:420-431, Loria, Psychoneuroendocrinology 1997 22:S103-S108, Luscher et al Mol. Immunol. 1983 20:1099-1105, Manna et al., J. Biol. Chem. 1999 274:5909-5918, Marschall et al., J. Biol. Chem. 1989 264:12989-12993, Medh et al., Cancer Res. 1998 15:3684-3693, Mohan et al., Steroids 1992 57:244-247, Munoz de Toro et al., J. Steroid Biochem. Mol. Biol. 1998 67:333-339, Padgett et al., J. Neuroimmunol. 1998 84:61, Padgett et al., Ann. N.Y. Acad. Sci. 1995 774:323, Padgett et al., J. Immunol. 1994 153:1544-1552, Pashko et al., Carcinogenesis 1984 5:463-466, Pashko et al., Carcinogenesis 1981 2:717, Petrylak et al., J. Clin. Oncology 1999 17:958-967, Podesta et al., Steroids 1996 61:622-626, Regelson et al., Ann. N.Y. Acad. Sci. 1994 719:564, Schmassmann et al., Gastroenterology 1993 104:1171-1181, Schmassmann et al., Hepatology 1990 11:989-996, Schreiber et al., Lancet 353:459-461, Schreiber, Neth. J. Med. 1998 53:S24-31, Schwartz et al., Cancer Res. 1988 48:4817, Shahidi et al., Biochem. Biophys. Res. Commun. 1999 254:559-565, Steer et al., Ann. Rheum. Dis. 1998 57:732-737, Suzuki et al., Steroids 1998 63:672-677, Suzuki et al., Steroids 1996 61:296-301, Swaan et al., Bioconjugate Chem. 1997 8:520-525, Tang et al, Anticancer Drug Res. 1998 13:815-824, Thomas et al., J. Steroid Biochem. 1986 25:103-108, Utsumi et al., Cancer Res. 1999 59:377-381, Vanden Heuvel, J. Nutr. 1999 129(2S Suppl.):575S-580S, Wang et al., Endocrinology 1998 139:3903-3912, Wong et al., J. Biol. Chem. 1999 274:5443-5453, Xie et al., Endocrinology 1999 140:219-227, Yen et al., Lipids 1977 12:409-413, Zackheim et al., Arch. Dermatology 1998 134:949-954, Zhang et al., Biochim. Biophys. Acta 1991 1096:179-186, Zhu et al., Carcinogenesis 1988 19:2101-2106.

Some proteins such as interleukin-6 (“IL-6”), erythropoietin (“EPO”) and thrombopoietin (“TPO”) have been examined for their capacity to enhance various aspects hematopoiesis, e.g., Hematology—Basic Principles and Practice, 3 rd edition, R. Hoffman, E. J. Benz Jr. et al., editors, Churchill Livingstone, N.Y., 2000 (see, e.g., Chapter 14 at pages 154-202), O. J. Borge et al., Blood 1996 88:2859-2870, M. Cremer et al., Ann. Hematol. 1999 78:401-407, Y. Sasaki et al., Blood 1999 94:1952-1960, U.S. Pat. No. 5,879,673. Recombinant IL-6 was shown in model systems to affect platelet counts in peripheral circulation, e.g., Stahl et al., Blood 1991 78:1467-1475, although significant toxicities are associated with its administration to humans, e.g., Andus et al., FEBS Lett. 1987 221:18, J. Gauldie et al., P.N.A.S. U.S.A. 1987 84:7251-7255, T. Geiger et al., Eur. J. Immunol. 1988 18:717-721. The IL-6 molecule has been described in detail, e.g., publication no. WO 88/00206. Administration of proteins is typically expensive, given factors such as the complexity of producing pharmaceutical grade material.

There is a current need for cost-effective pharmaceutical agents and treatment methods for treating various immune dysregulation conditions. The invention provides compounds that can be used in such treatments to treat or ameliorate one or more aspects of immune dysregulation conditions. The compounds can provide surprisingly unexpected beneficial effects, e.g., in preventing or reducing neutropenia in subjects such as mammals or primates. Such agents can be used to treat autoimmune or inflammation conditions, immune suppression conditions, infections, blood cell deficiencies and other described conditions. The agents and methods are useful to ameliorate these conditions or one or more symptoms associated with any of these conditions. The use of these agents can be combined with one or more conventional treatments for these disorders.

Summary of invention embodiments. In principal embodiments the invention provides therapeutic treatment methods.

The methods include a method to prevent, treat, ameliorate or slow the progression of cystic fibrosis, sickle cell disease, neutropenia or thrombocytpoenia in a subject, or to treat a symptom of the cystic fibrosis, sickle cell disease, neutropenia or thrombocytopenia, comprising administering to a subject, or delivering to the subject's tissues, an effective amount of a formula 1 compound having the structure 5, 6, 7, 8, 9, 10, 11, 12, 13 or 14

or a metabolic precursor or a metabolite thereof, wherein

R 10 moieties at the 5 (if present), 8, 9 and 14 positions respectively are in the α,α,α,α, α,α,α,β, α,α,β,α, α,β,α,α, β,α,α,α, α,α,β,β, α,β,α,β, β,α,α,β, β,α,β,α, β,β,α,α, α,β,β,α, α,β,β,β, β,α,β,β, β,β,α,β, β,β,β,α or β,β,β,β configurations,

wherein R 10A , R 10B , R 10C , R 10D and R 10E respectively are in the α,α, α,β, β,α or β,β configurations,

wherein, each R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 10 , R 10A , R 10B , R 10C , R 10D and R 10E independently are —H, —OH, —OR PR , —SR PR , —N(R PR ) 2 , —O—Si—(R 13 ) 3 , —CHO, —CHS, —CN, —SCN, —NO 2 , —NH 2 , —COOH, —OSO 3 H, —OPO 3 H, an ester, a thioester, a thionoester, a phosphoester, a phosphothioester, a phosphonoester, a phosphiniester, a sulfite ester, a sulfate ester, an amide, an amino acid, a peptide, an ether, a thioether, an acyl group, a thioacyl group, a carbonate, a carbamate, a halogen, an optionally substituted alkyl group, an optionally substituted alkenyl group, an optionally substituted alkynyl group, an optionally substituted aryl moiety, an optionally substituted heteroaryl moiety, an optionally substituted heterocycle, an optionally substituted monosaccharide, an optionally substituted oligosaccharide, a nucleoside, a nucleotide, an oligonucleotide, a polymer, or,

one more of R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 10 , R 10A , R 10B , R 10C , R 10D and R 10E are ═O, ═S, ═N—OH, ═CH 2 , ═CH—CH 3 , or an independently selected spiro ring and the hydrogen atom or the second variable group that is bonded to the same carbon atom is absent, or,

one or more of two adjacent R 1 -R 6 , R 10 , R 10A , R 10B , R 10C , R 10D and R 10E comprise an independently selected epoxide, acetal, a thioacetal, ketal or thioketal;

R 7 is —C(R 10 ) 2 —, —C(R 10 ) 2 —C(R 10 ) 2 —, —C(R 10 ) 2 —C(R 10 ) 2 —C(R 10 ) 2 —, —C(R 10 ) 2 —O—C(R 10 ) 2 —, —C(R 10 ) 2 —S—C(R 10 ) 2 —, —C(R 10 ) 2 —NR PR —C(R 10 ) 2 —, —O—, —O—C(R 10 ) 2 —, —S—, —S—C(R 10 ) 2 —, —NR PR — or —NR PR —C(R 10 ) 2 —;

R 8 and R 9 independently are —C(R 10 ) 2 —, —C(R 10 ) 2 —C(R 10 ) 2 —, —O—, —O—C(R 10 ) 2 —, —S—, —S—C(R 10 ) 2 —, —NR PR — or —NR PR —C(R 10 ) 2 —, or one or both of R 3 or R 9 independently are absent, leaving a 5-membered ring;

R 13 independently is C 1-6 alkyl; and

R PR independently is —H or a protecting group. In typical embodiments, one or two of R 10A , R 10B , R 10C , R 10D and R 10E are not hydrogen or one R 4 is —NH 2 , an optionally substituted amine, —N(R PR ) 2 , ═NOH, ═NO-optionally substituted alkyl, an amide or an N-linked amino acid.

Other embodiments include (1) certain new formula 1 compounds, which are new chemical entities, (2) compositions that comprise a formula 1 compound and another compound or an excipient, (3) formulations that comprise a formula 1 compound and 1, 2, 3, 4, 5, 6 or more excipients. The formulations can be designed for human pharmaceutical use or they can be suitable for veterinary use. Therapeutic use embodiments include (1) use of a formula 1 compound for the preparation of a medicament and (2) use of a formula 1 compound for the preparation of a medicament for the prophylaxis or treatment of a condition or symptom disclosed herein.

Other embodiments are as described elsewhere in the specification including the claims.

Definitions. As used herein and unless otherwise stated or implied by context, terms that are used herein have the meanings defined below. Unless otherwise contraindicated or implied, e.g., by including mutually exclusive elements or options, in these definitions and throughout this specification, the terms “a” and “an” mean one or more and the term “or” means and/or.

Reference to an androstane compound, e.g., 3β, 16α, 17β-trihydroxyandrostane, means that the hydrogen atom at the 5-position is in the α-configuration. For androstanes with hydrogen in the β-configuration, the compound name will specify this configuration, e.g., 3β, 16α, 17β-trihydroxy-5β-androstane.

An “invention formulation”, “formulation”, “pharmaceutical formulation” or the like means a composition that one can administer to a subject, e.g., human, mammal or other animal, without further manipulations that change the ingredients or the ingredient proportions that are present. Formulations will typically comprise a single formula 1 compound and one or more excipients. Formulations are suitable for human or veterinary applications and would typically have expected characteristics for the formulation, e.g., parenteral formulations for human use would usually be sterile and stored in a suitable closed container.

When referring to mixtures that contain a formula 1 compound, an “invention composition”, “composition” or the like means a composition, that is a formulation or that can be an intermediate one can use, e.g., to make a formulation or a formula 1 compound. Compositions also include other types of mixtures, e.g., (1) reagents for assays or cells that are optionally contacted with a formula 1 compound or mixtures of compounds and (2) compounds used to make a formula 1 compound or by-products of formula 1 compound synthesis or analysis. Invention compositions include compositions where further processing may be required before it is a formulation, e.g., mixing or addition of a desired amount of an excipient.

Phrases such as “administration of a compound of formula 1”, “treatment with a formula 1 compound”, “use of a formula 1 compound” or similar terms mean that the compound(s) is administered to, contacted with or delivered to, the subject or to the subject's cells or tissues in vitro or in vivo by one or more suitable methods, e.g., in vivo delivery can be by an oral, topical, subcutaneous, parenteral, buccal or sublingual route.

Expressions such as “a formula 1 compound(s)”, “a formula 1 compound” and the like mean invention compositions or formulations where one or more than one formula 1 compound is present, e.g., in a composition, or is used in the disclosed method, typically 1, 2, 3 or 4, usually 1. Any reference to a “formula 1 compound”, “one or more compounds of formula 1” or the like means that the formula 1 compound can have the formula 2 structure or any other structure disclosed herein that is within the definition of formula 1 compounds. The phrase formula 1 compound or formula 1 compound(s) is sometimes abbreviated as “F1C” or “F1C(s)” and formula 1 compounds may be abbreviated as “F1Cs”.

Reference to subject matter “as disclosed herein” such as a “therapeutic treatment or agent as disclosed herein”, a “dosing protocol as disclosed herein” or a “clinical condition or symptom as disclosed herein” or the like means a treatment, agent, protocol, condition, symptom or the like that is described herein or in any reference that is cited herein.

An “excipient”, “carrier”, “pharmaceutically acceptable excipient”, “pharmaceutically acceptable carrier” or similar terms mean one or more component(s) or ingredient(s) that is acceptable in the sense of being compatible with the other ingredients of invention compositions or formulations and not overly deleterious to the patient, animal, tissues or cells to which the F1C, composition or formulation is to be administered.

A “subject” means a human or animal. Usually the animal is a mammal or vertebrate such as a primate, rodent, lagomorph, domestic animal or game animal. Primates include chimpanzees, cynomologous monkeys, spider monkeys, and macaques, e.g., Rhesus or Pan . Rodents and lagomorphs include mice, rats, woodchucks, ferrets, rabbits and hamsters. Domestic and game animals include cows, horses, pigs, sheep, deer, bison, buffalo, mink, felines, e.g., domestic cat, canines, e.g., dog, wolf and fox, avian species, e.g., chicken, turkey, emu and ostrich, and fish, e.g., trout, catfish and salmon. Subject includes any subset of the foregoing, e.g., all of the above, but excluding one or more groups or species such as humans, primates or rodents. Other subsets of subjects include subjects of a given species or group of species of varying ages, e.g., young humans, e.g., about 1 week of age to about 9 years of age, adolescent humans, e.g., about 10-19 years of age, adult humans, e.g., about 20-100 years of age, and mature adult or elderly humans, e.g., at least about 55 years of age, at least about 60 years of age, at least about 65 years of age or a range of ages such as about 60-100 years of age. Thus, as used herein, prevention or treatment of a disease, condition or symptom may include or exclude any subset of subjects that are grouped by age.

The terms “effective amount”, “effective dose” or the like with reference to a F1C(s) mean an amount of the F1C(s) that is sufficient to elicit a desired response, e.g., detectable restoration of normal immune responsiveness in an immunodeficient subject to which it is administered, e.g., a human, or to detectable modulation or amelioration of an immune or cellular parameter or a clinical condition or symptom. An effective amount, e.g., for human therapeutic use, may be a single dose or two or more subdoses of a F1C administered in one day, or it may be administered as multiple doses over a period of time, e.g., over 1, 2, 3, 4 or about 7 days to about 1 year.

Terms such as “use”, “treat”, “treatment”, “address” or the like in the context of using the F1Cs in the treatment methods or other methods disclosed herein mean that a F1C is administered to a subject, delivered to the subject's tissues or contacted with tissues, cells or cell free systems in vivo or in vitro, e.g., as described herein or a reference cited herein. Typically such use or treatment results in, e.g., (1) detectable improvement in or amelioration of the condition or symptom being treated, (2) detectable modulation in the activity, level or numbers of a relevant biomolecule, therapeutic immune cell population or a pathological cell population, (3) slowing of the progression of a condition or delaying its onset, or reduction of the severity of a symptom(s) of the condition or (4) another detectable response as described herein. Any such amelioration may be transient, e.g., lasting for at least a few, e.g., about 1 to 24, hours or days, e.g., about 1, 2, 3, 4, 5, 6 or 7 days, or amelioration may be prolonged, e.g., lasting about 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 24, 26, 28, 35, 42, 49, 56 to about 60 days or more, or amelioration may be permanent. A treatment may slow the progression of a disease or symptom or it may reduce the severity thereof, e.g., onset of a disease or a symptom may be delayed in at least some subjects for about 1-24 hours, about 2-10 days, about 2-30 days or for about 1-5 years compared to subjects who are not treated with sufficient amounts of the F1C. Thus, a F1C use or treatment typically results in detectable modulation in a relevant immune parameter such as modulation of the level, activity or relative amount of a target effector or suppressor immune cell population, interleukin, cytokine, chemokine, immunoglobulin compared to a suitable control, e.g., untreated. A F1C treatment can also cause modulation of the level or activity of a relevant transcription factor, enzyme, cell biological activity or level or activity of the etiological agent of the disease such as a pathogen, tumor cell or autoreactive immune cell subset. A treatment with a F1C may be used to delay or prevent the onset of a disease, symptom or complication or to ameliorate or slow the progression of a preexisting disease, condition, symptom or complication, or to facilitate elimination of a disease, condition, symptom or complication.

“Ameliorate”, “amelioration”, “improvement” or the like means a detectable improvement or a detectable change consistent with improvement occurs in a subject or in at least a minority of subjects, e.g., in at least about 2%, 5%, 10%, 15%, 20%, 25%, 30%, 40%, 50%, 60%, 70%, 75%, 80%, 85%, 90%, 95%, 98%, 100% or in a range about between any two of these values. Such improvement or change may be observed in treated subjects as compared to subjects not treated with a F1C, where the untreated subjects have, or are subject to developing, the same or similar disease, condition, symptom or the like. Amelioration of a disease, condition, symptom or assay parameter may be determined subjectively or objectively, e.g., self assessment by a subject(s), by a clinician's assessment or by conducting an appropriate assay or measurement, including, e.g., a quality of life assessment, a slowed progression of a disease(s) or condition(s), a reduced severity of a disease(s) or condition(s), or a suitable assay(s) for the level or activity(ies) of a biomolecule(s), cell(s) or by detection of cell migration within a subject. Amelioration may be transient, prolonged or permanent or it may be variable at relevant times during or after a F1C is administered to a subject or is used in an assay or other method described herein or a cited reference, e.g., within about 1 hour of the administration or use of a F1C to about 3, 6, 9 months or more after a subject(s) has received a F1C.

The “modulation” of, e.g., a symptom, level or biological activity of a molecule, replication of a pathogen, cellular response, cellular activity or the like, means that the cell, level or activity, or the like is detectably increased or decreased. Such increase or decrease may be observed in treated subjects as compared to subjects not treated with a F1C, where the untreated subjects have, or are subject to developing, the same or similar disease, condition, symptom or the like. Such increases or decreases may be at least about 2%, 5%, 10%, 15%, 20%, 25%, 30%, 40%, 50%, 60%, 70%, 75%, 80%, 85%, 90%, 95%, 98%, 100%, 150%, 200%, 250%, 300%, 400%, 500%, 1000% or more or about within any range about between any two of these values. Modulation may be determined subjectively or objectively, e.g., by the subject's self assessment, by a clinician's assessment or by conducting an appropriate assay or measurement, including, e.g., quality of life assessments or suitable assays for the level or activity of molecules, cells or cell migration within a subject. Modulation may be transient, prolonged or permanent or it may be variable at relevant times during or after a F1C is administered to a subject or is used in an assay or other method described herein or a cited reference, e.g., within about 1 hour of the administration or use of a F1C to about 3, 6, 9 months or more after a subject(s) has received a F1C.

Terms such as “antigen”, “immunogen”, “antigenic fragment” or the like mean a molecule that comprises one or more epitopes that are capable of stimulating a subject's immune system to make, e.g., a secretory, humoral or cellular antigen-specific response against the antigen, immunogen or fragment. Antigenic fragments are synthetic or natural derivatives of natural or intact antigens or immunogens that retain at least a detectable capacity, e.g., at least about 10%, 20%, 30%, 40%, 50% or more of the native antigen's antigenic capacity, to stimulate a subject's immune system in a desired manner.

“Vaccine composition”, “vaccine” or similar terms mean an agent suitable for stimulating a subject's immune system to ameliorate a current condition or to protect against or to reduce present or future harm or infection, e.g., reduced tumor cell proliferation or survival, reduced pathogen replication or spread in a subject or a detectably reduced unwanted symptom(s) associated with a condition. Vaccines may modulate, typically detectably enhance, humoral, cell mediated or innate immune responses.

“Immunization” means the process of inducing a detectable and continuing moderate or high level of antibody or cellular immune response that is directed against an antigen to which the subject has been exposed. Such responses are typically detectably maintained for at least about 3-48 months or more.

At various locations in the present disclosure, e.g., in any disclosed embodiments or in the claims, reference is made to compounds, compositions, formulations, or methods that “comprise” one or more specified components, elements or steps. Invention embodiments also specifically include those compounds, compositions, formulations or methods that are or that consist of or that consist essentially of those specified components, elements or steps. The terms “comprising”, “consist of” and “consist essentially of” have their normally accepted meanings under U.S. patent law. For example, disclosed compositions or methods that “comprise” a component or step are open and they include or read on those compositions or methods plus an additional component(s) or step(s). Similarly, disclosed compositions or methods that “consist of” a component or step are closed and they would not include or read on those compositions or methods having appreciable amounts of an additional component(s) or an additional step(s).

“Alkyl” as used here means linked normal, secondary, tertiary or cyclic carbon atoms, i.e., linear, branched, cyclic or any combination thereof. Alkyl moieties, as used herein, may be saturated, or unsaturated, i.e., the moiety may comprise one, two, three or more independently selected double bonds or triple bonds. Unsaturated alkyl moieties include moieties as described for alkenyl and alkynyl moieties described below. The number of carbon atoms in an alkyl group or moiety can vary and typically is 1 to about 50, e.g., about 1-30 or about 1-20, unless otherwise specified, e.g., C 1-8 alkyl or C1-C8 alkyl means an alkyl moiety containing 1, 2, 3, 4, 5, 6, 7 or 8 carbon atoms. When an alkyl group is specified, species may include methyl, ethyl, 1-propyl (n-propyl), 2-propyl (i-propyl, —CH(CH 3 ) 2 ), 1-butyl (n-butyl), 2-methyl-1-propyl (i-butyl, —CH 2 CH(CH 3 ) 2 ), 2-butyl (s-butyl, —CH(CH 3 )CH 2 CH 3 ), 2-methyl-2-propyl (t-butyl, —C(CH 3 ) 3 ), 1-pentyl (n-pentyl), 2-pentyl (—CH(CH 3 )CH 2 CH 2 CH 3 ), 3-pentyl (—CH(CH 2 CH 3 ) 2 ), 2-methyl-2-butyl (—C(CH 3 ) 2 CH 2 CH 3 ), 3-methyl-2-butyl (—CH(CH 3 )CH(CH 3 ) 2 ), 3-methyl-1-butyl (—CH 2 CH 2 CH(CH 3 ) 2 ), 2-methyl-1-butyl (—CH 2 CH(CH 3 )CH 2 CH 3 ), 1-hexyl, 2-hexyl (—CH(CH 3 )CH 2 CH 2 CH 2 CH 3 ), 3-hexyl (—CH(CH 2 CH 3 )(CH 2 CH 2 CH 3 )), 2-methyl-2-pentyl (—C(CH 3 ) 2 CH 2 CH 2 CH 3 ), 3-methyl-2-pentyl (—CH(CH 3 )CH(CH 3 )CH 2 CH 3 ), 4-methyl-2-pentyl (—CH(CH 3 )CH 2 CH(CH 3 ) 2 ), 3-methyl-3-pentyl (—C(CH 3 )(CH 2 CH 3 ) 2 ), 2-methyl-3-pentyl (—CH(CH 2 CH 3 )CH(CH 3 ) 2 ), 2,3-dimethyl-2-butyl (—C(CH 3 ) 2 CH(CH 3 ) 2 ), 3,3-dimethyl-2-butyl (—CH(CH 3 )C(CH 3 ) 3 ), cyclopropyl (—CH<CH 2 CH 2 ), cyclobutyl (—CH<CH 2 CH 2 CH 2 ), cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, —(CH 2 ) n —(CHCH 3 ) m —(CH 2 ) o —CH 3 , —(CH 2 ) n —(CHC 2 H 5 ) m —(CH 2 ) o —CH 3 and species and groups described below for alkenyl, alkynyl groups aryl groups, arylalkyl groups alkylaryl groups and the like, where n, m and o independently are 0, 1, 2, 3, 4, 5, 6, 7 or 8.

For any group or moiety described by a given range of carbon atoms, the designated range means that any individual number of carbon atoms is described. Thus, reference to, e.g., “C1-C4 optionally substituted alkyl”, “C 2-6 alkenyl”, or “C2-C6 optionally substituted alkenyl”, specifically means that a 1, 2, 3 or 4 carbon optionally substituted alkyl moiety as defined herein is present, or a 2, 3, 4, 5 or 6 carbon alkenyl or optionally substituted alkenyl moiety as defined herein is present. All such designations are expressly intended to disclose all of the individual carbon atom groups and thus “C1-C4 optionally substituted alkyl” means, e.g., 3 carbon alkyl, 4 carbon substituted alkyl and the like are disclosed and can be expressly referred to or named.

“Alkenyl” as used here means a moiety that comprises linked normal, secondary, tertiary or cyclic carbon atoms, i.e., linear, branched, cyclic or any combination thereof, that comprises one or more double bonds (e.g., —CH═CH—), e.g., 1, 2, 3, 4, 5, 6 or more, typically 1 or 2. The number of carbon atoms in an alkenyl group or moiety can vary and typically is 2 to about 50, e.g., about 2-30 or about 2-20, unless otherwise specified, e.g., C 2-8 alkenyl or C2-8 alkenyl means an alkenyl moiety containing 2, 3, 4, 5, 6, 7 or 8 carbon atoms. When an alkenyl group is specified, species may include methylene (═CH 2 ), methylmethylene (═CH—CH 3 ), ethylmethylene (═CH—CH 2 —CH 3 ), ═CH—CH 2 —CH 2 —CH 3 , vinyl (—CH═CH 2 ), allyl, —(CH 2 ) n —(CH═CH)—(CH 2 ) m —CH 3 , —(CH 2 ) n —(CCH 3 ═CH)—(CH 2 ) m —CH 3 , —(CH 2 ) n —(CH═CCH 3 )—(CH 2 ) m —CH 3 and —(CH 2 ) n —(CH═CH) 0-1 —(CH 2 ) m —CH 2 CH═CH 2 , where n and m independently are 0, 1, 2, 3, 4, 5, 6, 7 or 8.

“Alkynyl” as used here means a moiety that comprises linked normal, secondary, tertiary or cyclic carbon atoms, i.e., linear, branched, cyclic or any combination thereof, that comprises one or more triple bonds (—C≡C—), e.g., 1, 2, 3, 4, 5, 6 or more, typically 1 or 2 triple bonds, optionally comprising 1, 2, 3, 4, 5, 6 or more double bonds, with the remaining bonds being single bonds. The number of carbon atoms in an alkenyl group or moiety can vary and typically is 2 to about 50, e.g., about 2-30 or about 2-20, unless otherwise specified, e.g., C 2-8 alkynyl or C2-8 alkynyl means an alkynyl moiety containing 2, 3, 4, 5, 6, 7 or 8 carbon atoms. When an alkynyl group is specified, groups and species may include —CCH, —CCCH 3 , —CCCH 2 CH 3 , —CCC 3 H 7 , —CCCH 2 C 3 H 7 , —(CH 2 ) n —(C≡C)—(CH 2 ) m —CH 3 , and —(CH 2 ) n —(C≡C) 0-1 —(CH 2 ) m —CH 2 C≡CH, where n and m independently are 0, 1, 2, 3, 4, 5, 6, 7 or 8.

“Aryl” means an aromatic ring or fused ring system with no ring heteroatoms, e.g., phenyl or naphthyl.

“Arylalkyl” means a moiety where an alkyl group is bonded to an aryl group, i.e., -alkyl-aryl, where alkyl and aryl groups are as described above, e.g., —CH 2 —C 6 H 5 or —CH 2 CH(CH 3 )—C 6 H 5 .

“Alkylaryl” means a moiety where an aryl group is bonded to an alkyl group, i.e., -aryl-alkyl, where aryl and alkyl groups are as described above, e.g., —C 6 H 4 —CH 3 or —C 6 H 4 —CH 2 CH(CH 3 ).

“Substituted alkyl”, “substituted alkenyl”, “substituted alkynyl”, substituted alkylaryl”, “substituted arylalkyl”, “substituted heterocycle”, “substituted aryl”, “substituted monosaccharide” and the like mean an alkyl, alkenyl, alkynyl, alkylaryl, arylalkyl heterocycle, aryl, monosaccharide or other group or moiety as defined or disclosed herein that has a substituent(s) that replaces a hydrogen atom(s) or a substituent(s) that interrupts a carbon atom chain. Substituted heterocycles may thus have a substituent bonded to a ring carbon or a ring heteroatom such as a nitrogen. Substituents for any of these moieties include 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 or more independently selected —O—, —S—, —NH—, —C(O)—, —C(O)OH, —C(O)OR 15A , C(O)OR PR , C(O)SR 15A , C(O)SR PR , CHO, —CHS, —CH 2 SH, —C═N—, —OH, ═O, —OR 15A , —OR PR , —C(O)OR PR , —O—C(O)H, —C(O)CH 3 , —C(S)CH 3 , —C(S)SH, C(S)SR 15A , C(S)SR PR , C(O)CH 2 OH, —C(O)CH 2 F, —C(O)CH 2 Cl, —C(O)CH 2 Br, —C(O)CH 2 I, —C(O)CF 2 H, —C(O)CF 3 , —C(O)NHCH 3 , —C(O)NHC 2 H 5 , —C(O)NHC(CH 3 ) 3 , —O—CH 2 —C(O)—C(CH 3 ) 3 , —C(O)—C(CH 3 ) 3 , —O—CH(CH 3 )—O—C(CH 3 ) 3 , —C(O)O—, C(S)OR PR , —C(S)O—, —OC(O)—, —C(O)H, —OCH 2 —, —CH 2 —O—CH 2 —, —(CH 2 ) 1-2 —O—(CH 2 ) 2 , —OCH 2 CH 2 —, —OCH 2 O—, —OCH 2 CH 2 O—, —CH 2 OH, —CH 2 F, —CHF 2 , —CF 3 , —CH 2 Cl, —CH 2 Br, —CH 2 I, —C 2 H 4 Cl, —C 2 H 4 Br, —C 2 H 4 I, —CH 2 CH 2 F, —CH 2 CHF 2 , —CH 2 CF 3 , —NH 2 , —NHR 15A , —N(R 15A ) 2 , —N(R PR ) 2 , —NHR PR , —NHC(O)—, —CH 2 —NR PR , —CH 2 —NHR PR , —CH 2 —NHC(O)—, —C(O)NH—, —C(O)NHR PR , —OC(O)NR PR , —OC(O)NHR PR , —C(═NH)—NH 2 , —C(═NH)OH, —C(═N—NH 2 )OH, —C(O)NHOH, ═NOH, ═NOCH 3 , ═NOC 2 H 5 , ═NOC 3 H 7 , ═NOC 4 H 9 , —NHR 15A , ═NR 15A , ═N—, —NR PR C(O)NR PR —, —NR PR C(O)NHR PR , —NR PR CH 2 —, —NR PR CH 2 CH 2 —, —NO 2 , —ONO 2 , —S—, —SH, —SR 15A , —SR PR , ═S, —S(O)R 15A , —S(O)OR 15A , —S(O)—, —S(O)(O)—, —O—S(O)(O)—NR PR —, —O—S(O)(O)—NR PR —CH 2 —, —CH 2 —S(O)(O)H, —CH 2 —NH—S(O)(O)H, —CHR 15A , —NH—S(O)(O)H, —O—S(O)(O)—CHR 15A —, —CH, R 15A —O—S(O)(O)—, —CHR 15A —S(O)(O)—CHR 15A —, —S(O)(O)H, —CHR 15A —S(O)(O)H, —NH—S(O)(O)—NH—, —CHR 15A —NH—S(O)(O)—NH—, —CHR 15A —NH—S(O)(O)—NH—CHR 15A , —NH—S(O)(O)—NHR PR , —NH—S(O)(O)—NH 2 , —NH—S(O)(O)—NHCH 3 , —NH—S(O)—NH—, —CHR 15A —NH—S(O)—NH—, —CHR 15A —NH—S(O)—NH—CHR 15A , —NH—S(O)—NHR PR , —NH—S(O)—NH 2 , —NH—S(O)—NHCH 3 , —NH—S(O)—, —CHR 15A —NH—S(O)—, —NH—S(O)—CHR 15A , —S(O)—NHR PR , —S(O)—NH 2 , —S(O)—NHCH 3 , —S(O)(O)—O—, —S(O)OR PR , —S(O)(O)OH, —OSO 3 H 2 , —S(O)(O)OR 15A , —S(O)(O)OR PR , —S(O)OH, —S(O)OR 15A , —S(O)OR PR , —S(O)R 15A , —S(O)R PR , —CN, —SCN, —C(O)OH, —C(O)OR 15A , —C(O)OR PR , —C(O)SH, —C(O)SR 15A , —C(O)SR PR , —C(S)OH, —C(S)OR 15A , —C(S)OR PR , —O—P(O)(O)OH, —O—P(O)(O)OR 15A , —O—P(O)(O)OR 15A , —O—P(S)(O)OH, —O—P(S)(O)OR 15A , —O—P(S)(O)OR PR , —O—P(O)(O)SH, —O—P(O)(O)SR 15A , —P(O)(O)SR PR , —F, —Cl, —Br, —I, —C═NH, —C═NCH 3 , —C═NC 2 H 5 , —C(═S)—, —C 6 H 5 , —CH 2 C 6 H 5 , —O-A8, —S-A8, —C(O)-A8, —OC(O)-A8, —C(O)O-A8, —OPO 3 (R PR ) 2 , -amino acid-, —O-monosaccharide, —O-disaccharide, —S-monosaccharide, —S-disaccharide, a polymer, e.g., a PEG, and combinations of these moieties and salts on any of these moieties that can form a salt, where each R PR independently is —H, an independently selected protecting group or both R PR together are a protecting group, A8 is C1-C10 optionally substituted alkyl, and R 15A independently are —H, —CH 3 , —C 2 H 5 , —C 3 H 7 , —C 4 H 9 , —C(CH 3 ) 3 , —CH 2 OH, —C 2 H 4 OH, —C 3 H 6 OH, —C 4 H 8 OH —C(CH 2 OH)(CH 3 ) 2 , —C 3 H 5 , —C 4 H 7 , optionally substituted C1-10 alkyl, C1-10 perfluoroalkyl, optionally substituted aryl, optionally substituted C1-12 alkylaryl, optionally substituted C1-12 arylalkyl, optionally substituted allyl, optionally substituted heterocycle, optionally substituted C1-4 alkyl-optionally substituted heterocycle or optionally substituted heterocycle-optionally substituted C1-4 alkyl. Substituents are independently chosen when more than one is present. Alkenyl and alkynyl groups that comprise a substituent(s), are optionally substituted at a carbon that is one or more methylene moiety removed from the double bond, e.g., the substituent is optionally separated by one, two, three or more independently selected —CH 2 —, —CH(C 1-6 optionally substituted alkyl)-, —CH(C 1-6 optionally substituted alkenyl)-, —CH(C 1-6 optionally substituted alkynyl)-, —CH(optionally substituted heterocycle)-, —CH(optionally substituted aryl-optionally substituted alkyl)- or —CH(optionally substituted alkyl-optionally substituted aryl)- moieties. Other substituted alkenyl and alkynyl moieties include ═CHOH, ═CH-halogen, ═CH—COOR PR , ═CH—(CH 2 ) m —NH 2 , ═CH—(CH 2 ) m —NH(C1-C6 alkyl), ═CH—N(C1-C6 alkyl) 2 , ═CH—CH 2 OH, ═CH—CH 2 -halogen, ═CH—CH 2 —COOR PR , ═CH—CH 2 —NH 2 , ═CH—CH 2 —NH(C1-C6 alkyl), ═CH—CH 2 —N(C1-C6 alkyl) 2 , ═CH—CH 2 —CH 2 OH, ═CH—CH 2 —CH 2 -halogen, ═CH—CHOH—CH 3 , ═CH—CHOH—CH 2 —CH 3 , ═CH—CH 2 —CH 2 —COOR PR , ═CH—CH 2 —CH 2 —NH 2 , ═CH—CH 2 —CH 2 —N(C1-C4 alkyl) 2 , —CH═CH—(CH 2 ) m —OH, —CH═CH-halogen, —CH═CH—CH 2 OH, —CH═CH—CH 2 -halogen, —C≡C-halogen, —C≡C—CH 2 —NH 2 , —C≡C—CH 2 —NH(C1-C6 alkyl), —C≡C—CH 2 —N(C1-C6 alkyl) 2 , —C≡C—OH, —C≡C—COOR PR , —C≡C—CH 2 -halogen, —C≡C—CH 2 —OH and —C≡C—CH 2 —COOR PR , where each alkyl moiety is the same or different, e.g., both are methyl, ethyl or propyl or one is methyl and the other is ethyl, propyl or butyl and m is 1, 2, 3 or 4. The organic moieties and substitutions described here, and for other any other moieties described herein, usually will exclude obviously unstable moieties, e.g., —O—O—, except where such unstable moieties are transient species that one can use to make a compound such as a F1C with sufficient chemical stability for the one or more of the uses described herein.

“Heterocycle” or “heterocyclic” includes by way of example and not limitation the heterocycles described in Paquette, Leo A.; “Principles of Modern Heterocyclic Chemistry” (W. A. Benjamin, New York, 1968), particularly Chapters 1, 3, 4, 6, 7, and 9; “The Chemistry of Heterocyclic Compounds, A series of Monographs” (John Wiley & Sons, New York, 1950 to present), in particular Volumes 13, 14, 16, 19, and 28; and J. Am. Chem. Soc. 1960, 82:5566. Heterocycles are typically bonded to the steroid nucleus through a carbon, nitrogen or sulfur atom in the heterocycle ring.

Examples of heterocycles include by way of example and not limitation pyridyl, thiazolyl, tetrahydrothiophenyl, sulfur oxidized tetrahydrothiophenyl, pyrimidinyl, furanyl, thienyl, pyrrolyl, pyrazolyl, imidazolyl, tetrazolyl, benzofuranyl, thianaphthalenyl, indolyl, indolenyl, quinolinyl, isoquinolinyl, benzimidazolyl, piperidinyl, 4-piperidonyl, pyrrolidinyl, 2-pyrrolidonyl, pyrrolinyl, tetrahydrofuranyl, tetrahydroquinolinyl, tetrahydroisoquinolinyl, decahydroquinolinyl, octahydroisoquinolinyl, azocinyl, triazinyl, 6H-1,2,5-thiadiazinyl, 2H,6H-1,5,2-dithiazinyl, thienyl, thianthrenyl, pyranyl, isobenzofuranyl, chromenyl, xanthenyl, phenoxathiinyl, 2H-pyrrolyl, isothiazolyl, isoxazolyl, pyrazinyl, pyridazinyl, indolizinyl, isoindolyl, 3H-indolyl, 1H-indazoly, purinyl, 4H-quinolizinyl, phthalazinyl, naphthyridinyl, quinoxalinyl, quinazolinyl, cinnolinyl, pteridinyl, 4aH-carbazolyl, carbazolyl, β-carbolinyl, phenanthridinyl, acridinyl, pyrimidinyl, phenanthrolinyl, phenazinyl, phenothiazinyl, furazanyl, phenoxazinyl, isochromanyl, chromanyl, imidazolidinyl, imidazolinyl, pyrazolidinyl, pyrazolinyl, piperazinyl, indolinyl, isoindolinyl, quinuclidinyl, morpholinyl, oxazolidinyl, benzotriazolyl, benzisoxazolyl, oxindolyl, benzoxazolinyl, and isatinoyl.

By way of example and not limitation, carbon bonded heterocycles are bonded at position 2, 3, 4, 5, or 6 of a pyridine, position 3, 4, 5, or 6 of a pyridazine, position 2, 4, 5, or 6 of a pyrimidine, position 2, 3, 5, or 6 of a pyrazine, position 2, 3, 4, or 5 of a furan, tetrahydrofuran, thiofuran, thiophene, pyrrole or tetrahydropyrrole, position 2, 4, or 5 of an oxazole, imidazole or thiazole, position 3, 4, or 5 of an isoxazole, pyrazole, or isothiazole, position 2 or 3 of an aziridine, position 2, 3, or 4 of an azetidine, position 2, 3, 4, 5, 6, 7, or 8 of a quinoline or position 1, 3, 4, 5, 6, 7, or 8 of an isoquinoline. Still more typically, carbon bonded heterocycles include 2-pyridyl, 3-pyridyl, 4-pyridyl, 5-pyridyl, 6-pyridyl, 3-pyridazinyl, 4-pyridazinyl, 5-pyridazinyl, 6-pyridazinyl, 2-pyrimidinyl, 4-pyrimidinyl, 5-pyrimidinyl, 6-pyrimidinyl, 2-pyrazinyl, 3-pyrazinyl, 5-pyrazinyl, 6-pyrazinyl, 2-thiazolyl, 4-thiazolyl, or 5-thiazolyl.

By way of example and not limitation, nitrogen bonded heterocycles are bonded at position 1 of an aziridine, azetidine, pyrrole, pyrrolidine, 2-pyrroline, 3-pyrroline, imidazole, imidazolidine, 2-imidazoline, 3-imidazoline, pyrazole, pyrazoline, 2-pyrazoline, 3-pyrazoline, piperidine, piperazine, indole, indoline, 1H-indazole, position 2 of a isoindole, or isoindoline, position 4 of a morpholine, and position 9 of a carbazole, or β-carboline. Typically, nitrogen bonded heterocycles include 1-aziridyl, 1-azetedyl, 1-pyrrolyl, 1-imidazolyl, 1-pyrazolyl, and 1-piperidinyl.

“Heteroaryl” means an aromatic ring or two or more fused rings that contain one or more aromatic rings where the ring or fused rings comprise 1, 2, 3 or more heteroatoms, usually oxygen (—O—), nitrogen (—NX—) or sulfur (—S—) where X is —H, a protecting group or C 1-6 optionally substituted alkyl, usually —H. Examples are as described for heterocycle.

“Alcohol” as used herein means an alcohol that comprises a C 1-12 alkyl moiety substituted at a hydrogen atom with one hydroxyl group. Alcohols include methanol, ethanol, n-propanol, i-propanol, n-butanol, i-butanol, s-butanol, t-butanol, n-pentanol, i-pentanol, n-hexanol, cyclohexanol, n-heptanol, n-octanol, n-nonanol and n-decanol. The carbon atoms in alcohols can be straight, branched or cyclic. Alcohol includes any subset of the foregoing, e.g., C 1-4 alcohols (alcohols having 1, 2, 3 or 4 carbon atoms).

“Halogen” means fluorine, chlorine, bromine or iodine.

“Protecting group” means a moiety that prevents or reduces the atom or functional group to which it is linked from participating in unwanted reactions. For example, for —OR PR , R PR may be hydrogen or a protecting group for the oxygen atom found in a hydroxyl, while for —C(O)—OR PR , R PR may be hydrogen or a carboxyl protecting group, for —SR PR , R PR may be hydrogen or a protecting group for sulfur in thiols for instance, and for —NHR PR or —N(R PR ) 2 —, R PR may be hydrogen or a nitrogen atom protecting group for primary or secondary amines. Hydroxyl, amine, ketones and other reactive groups are found in F1Cs at, e.g., R 1 or R 2 . These groups may require protection against reactions taking place elsewhere in the molecule. The protecting groups for oxygen, sulfur or nitrogen atoms are usually used to prevent unwanted reactions with electrophilic compounds, such as acylating agents used, e.g., in steroid chemistry.

“Ester” means a moiety that contains a —C(O)—O— structure. Typically, esters as used here comprise an organic moiety containing about 1-50 carbon atoms (e.g., about 2-20 carbon atoms) and 0 to about 10 independently selected heteroatoms (e.g., O, S, N, P, Si), where the organic moiety is bonded to a formula 1 steroid nucleus at, e.g., R 1 or R 2 through the —C(O)—O— structure, e.g., organic moiety-C(O)—O-steroid or organic moiety-O—C(O)-steroid. The organic moiety usually comprises one or more of any of the organic groups described herein, e.g., C 1-20 alkyl moieties, C 2-20 alkenyl moieties, C 2-20 alkynyl moieties, aryl moieties, C 2-9 heterocycles or substituted derivatives of any of these, e.g., comprising 1, 2, 3, 4 or more substituents, where each substituent is independently chosen. Exemplary substitutions for hydrogen or carbon atoms in these organic groups are as described above for substituted alkyl and other substituted moieties. Substitutions are independently chosen. The organic moiety includes compounds defined by the R 4 variable. The organic moieties exclude obviously unstable moieties, e.g., —O—O—, except where such unstable moieties are transient species that one can use to make a compound with sufficient chemical stability for one or more of the uses described herein, including for synthesis of the formula 1 or other compounds. The substitutions listed above are typically substituents that one can use to replace one or more carbon atoms, e.g., —O— or —C(O)—, or one or more hydrogen atom, e.g., halogen, —NH 2 or —OH. Exemplary esters include one or more independently selected acetate, enanthate, propionate, isopropionate, isobutyrate, butyrate, valerate, caproate, isocaproate, hexanoate, heptanoate, octanoate, nonanoate, decanoate, undecanoate, phenylacetate or benzoate, which are typically hydroxyl esters.

“Thioester” means a moiety that comprises a —C(O)—S— structure. Typically, thioesters as used here comprise an organic moiety containing about 1-50 carbon atoms (e.g., about 1-20 carbon atoms) and 0 to about 10 independently selected heteroatoms (e.g., O, S, N, P, Si), where the organic moiety is bonded to a formula 1 steroid nucleus at a variable group such as R 1 , R 2 , R 3 , R 4 or R 10 through the —C(O)—S— structure, e.g., organic moiety-C(O)—S-steroid or organic moiety-S—C(O)-steroid. The organic moiety is as described above for esters.

“Thionoester” means a moiety that comprises a —C(S)—O— structure. Typically, thionoesters as used here comprise an organic moiety containing about 1-50 carbon atoms (e.g., about 1-20 carbon atoms) and 0 to about 10 independently selected heteroatoms (e.g., O, S, N, P, Si), where the organic moiety is bonded to a formula 1 steroid nucleus at a variable group such as R 1 , R 2 , R 3 , R 4 or R 10 through the —C(S)—O—structure, e.g., organic moiety-C(S)—O-steroid or organic moiety-O—C(S)-steroid. The organic moiety is as described above for esters.

“Acetal”, “thioacetal”, “ketal”, “thioketal” “spiro ring” and the like mean a cyclic organic moiety that is bonded to a steroid ring atom in the F1Cs, e.g., steroid nucleus atoms at one, two or more of the 1, 2, 3, 4, 6, 7, 11, 12, 15, 16, 17, 18 or 19 positions. Typically, acetals comprise an organic moiety containing about 1-20 carbon atoms (e.g., about 1-10 carbon atoms) and 0 to about 10 independently selected heteroatoms (e.g., O, S, N, P, Si). For acetals (or ketals), the steroid nucleus atoms are usually carbons and the acetal is bonded to a steroid carbon through two oxygen atoms. Thioacetals (or thioketals) are bonded to the steroid nucleus through one oxygen and one sulfur atom or, more often, through two sulfur atoms. One, two or more of e.g., R 1 , R 2 , R 3 , R 4 , R 10 at the 2, 11 or 15 positions, R 10A , R 10B , R 10C and R 10D , may be an independently selected acetal, thioacetal or spiro ring in any of the F1Cs disclosed herein. The oxygen or sulfur atoms in ketals and thioketals are linked by an optionally substituted alkyl moiety. Typically the alkyl moiety is an optionally substituted C1-C6 alkylene or branched alkyl structure such as —C(CH 3 ) 2 —, —CH(CH 3 )—, —CH 2 —, —CH 2 —CH 2 —, —C[(C2-C4 alkyl) 2 ] 1, 2, 3 - or —[CH(C2-C4 alkyl)] 1, 2, 3 —. Acetals include moieties having the structure —O—[C(R 36 ) 2 ] 1-6 —O—, —O—CH 2 —[C(R 36 ) 2 ] 2 —O—, —O—CH 2 —CH 2 —[C(R 36 ) 2 ] 2 —O—, —O—CH 2 —[C(R 36 ) 2 ] 2 —CH 2 —O—, and —O—CH 2 —C(R 36 ) 2 —O—, where each R 36 independently is —H, —OH, ═O, ═S, —SH, —F, —Cl, —Br, —I or an organic moiety such as C1-C6 alkyl (e.g., methyl, ethyl, hydroxymethyl or halomethyl), C2-C6 alkenyl, C2-C6 alkenyl, aryl or an heterocycle, any of which are optionally substituted, e.g., —CF 3 or —CH 2 OH. In some of these embodiments, one R 36 is —H and the other is another atom or moiety, e.g., —OH, methyl or a halogen. In other embodiments, neither R 36 is —H, e.g., both are methyl. Thioacetals include moieties that comprise a —S—[C(R 36 ) 2 ] 1-6 —O— or —S—[C(R 36 ) 2 ] 1-6 —S— structure where the open valences are bonded to the same carbon on the steroid nucleus. Typically, thioacetals as used here comprise an organic moiety containing about 1-50 carbon atoms (e.g., about 2-20 carbon atoms) and 0 to about 10 independently selected heteroatoms (e.g., O, S, N, P, Si), where the organic moiety is bonded to a formula 1 steroid nucleus at variable groups such as R 1 , R 2 , R 3 , R 4 or R 10 through the —S—[C(R 36 ) 2 ] m —O— or —S—[C(R 36 ) 2 ] m —S— structure, e.g., 17-steroid-S—[C(R 36 ) 2 ] m —O-17-steroid, 17-steroid-S—CH 2 —CH 2 —O-17-steroid, 17-steroid-O—[C(R 36 ) 2 ] m —S-17-steroid, 17-steroid-S—[C(R 36 ) 2 ] m —S-17-steroid, 17-steroid-S—[C(R 36 ) 2 ] m —O-17-steroid, where m is 1, 2, 3, 4, 5 or 6. The organic moiety is as described above for esters. Other exemplary acetal and thioacetals are —O—C(CH 3 ) 2 —O—, —O—CH 2 —CH 2 —CH 2 —O—, —O—CH 2 —CH 2 —O—, —O—CH 2 —O—, —O—C(CH 3 )(heterocycle)-O—, —O—CH (heterocycle)-O—, —O—C(CH 3 )(aryl)-O—, —O—CH (aryl)-O—, —S—C(CH 3 ) 2 —O—, —S—C(CH 3 ) 2 —S—, —S—CH 2 —CH 2 —O—, —S—CH 2 —CH 2 —S—, —S—CH 2 —O—, —S—CH 2 —S—, —O—C(CH 3 ) 2 —CH 2 —O—, —O—C(CH 3 ) 2 —C(CH 3 ) 2 —O—, —S—C(CH 3 ) 2 —CH 2 —O— and —O—C(CH 3 ) 2 —CH 2 —S—. Some of these moieties can serve as protecting groups for a ketone or hydroxyl, e.g., acetals such as —O—CH 2 —CH 2 —CH 2 —O— or —O—CH 2 —CH 2 —O— for ketones, which form a spiro ring that can be removed by chemical synthesis methods or by metabolism in cells or biological fluids. For any spiro ring disclosed herein and unless otherwise specified, the 1 st and 2 nd open valences can be bonded to the carbon in the steroid nucleus in the α- and β-configurations respectively or in the α- and β-configurations respectively. For example, in a spiro —NH—CH 2 —CH 2 —O— structure, the 1 st open valence, i.e., at the nitrogen atom, can be, e.g., at the 17-position in the β-configuration and the 2 nd open valence, i.e., at the oxygen, would then be in the α-configuration.

“Phosphoester” or “phosphate ester” means a moiety that comprises a —O—P(OR PR )(O)—O— structure where R PR is hydrogen (—H), a protecting group or an organic moiety as described for esters. Typically, phosphoesters as used here comprise a hydrogen atom, a protecting group or an organic moiety containing about 1-50 carbon atoms and 0 to about 10 independently selected heteroatoms (e.g., O, S, N, P, Si) linked to a formula 1 steroid nucleus at a variable group such as R 1 -R 6 , R 10 , R 15 , R 17 or R 18 through the —O—P(O)(O)—O— structure, e.g., organic moiety-O—P(O)(OH)—O-steroid. The organic moiety is as described above for esters. Exemplary phosphoesters include —O—P(O)(OH)—O—CH 3 , —O—P(O)(OCH 3 )—O—CH 3 , —O—P(O)(OH)—O—CH 2 —CH 3 , —O—P(O)(OC 2 H 5 )—O—CH 2 —CH 3 , —O—P(O)(OH)—O—CH 2 —CH 2 —CH 3 , —O—P(O)(OH)—O—CH(CH 3 )—CH 3 , —O—P(O)(OH)—O—CH 2 —CH 2 —CH 2 —CH 3 , —O—P(O)(O(CH 3 ) 3 )—O—C(CH 3 ) 3 and —O—P(O)(OH)—O—C(CH 3 ) 3 .

“Phosphothioester” means a moiety that comprises a —O—P(SR PR )(O)—O— structure where R PR is —H, a protecting group or an organic moiety as described for esters. Typically, phosphothioesters as used here comprise a hydrogen atom, a protecting group or an organic moiety containing about 1-50 carbon atoms and 0 to about 10 independently selected heteroatoms (e.g., O, S, N, P, Si) linked to a formula 1 steroid nucleus at a variable group such as R 1 -R 6 , R 10 , R 15 , R 17 or R 18 through the —O—P(O)(O)—O— structure, e.g., organic moiety-O—P(O)(SH)—O-steroid. The organic moiety is as described above for esters. Exemplary phosphothioesters are as described for phosphoesters, except that sulfur replaces the appropriate oxygen atom.

“Phosphonoester” means a moiety that comprises a —P(OR PR )(O)— structure where R PR is —H, a protecting group or an organic moiety as described for esters. Typically, phosphonoesters as used here comprise a hydrogen atom, a protecting group or an organic moiety containing about 1-50 carbon atoms and 0 to about 10 independently selected heteroatoms (e.g., O, S, N, P, Si) linked to a formula 1 steroid nucleus at a variable group such as R 1 -R 6 , R 10 , R 15 , R 17 or R 18 through the —P(OR PR )(O)—O— structure, i.e., organic moiety-P(OR PR )(O)—O-steroid or steroid-P(OR PR )(O)—O-organic moiety. The organic moiety is as described above for esters.

“Phosphiniester” means a moiety that comprises a —P(O)H— structure where R PR is —H, a protecting group or an organic moiety as described for esters. Typically, phosphiniesters as used here comprise a hydrogen atom, a protecting group or an organic moiety containing about 1-50 carbon atoms and 0 to about 10 independently selected heteroatoms (e.g., O, S, N, P, Si) linked to a formula 1 steroid nucleus at a variable group such as R 1 -R 6 , R 10 , R 15 , R 17 or R 18 through the —P(O)H— structure, i.e., organic moiety-P(O)H-steroid or steroid-P(O)H-organic moiety. The organic moiety is as described above for esters.

“Sulfate ester” means a moiety that comprises a —O—S(O)(O)—O— structure. Typically, sulfate esters as used here comprise a hydrogen atom, a protecting group or an organic moiety containing about 1-50 carbon atoms and 0 to about 10 independently selected heteroatoms (e.g., O, S, N, P, Si) linked to a formula 1 steroid nucleus at a variable group such as R 1 -R 6 , R 10 , R 15 , R 17 or R 18 through the —O—S(O)(O)—O— structure, e.g., organic moiety-O—S(O)(O)—O-steroid. The organic moiety is as described above for esters.

“Sulfite ester” means a moiety that comprises a —O—S(O)—O— structure. Typically, sulfite esters as used here comprise an organic moiety containing about 1-50 carbon atoms and 0 to about 10 independently selected heteroatoms (e.g., O, S, N, P, Si) linked to a formula 1 steroid nucleus at a variable group such as R 1 -R 6 , R 10 , R 15 , R 17 or R 18 through the —O—S(O)—O— structure, e.g., organic moiety-O—S(O)—O-steroid. The organic moiety is as described above for esters.

“Sulfamate ester”, “sulfamate derivative”, “sulfamate” and the like mean a moiety that comprises a —O—S(O)(O)—NH— or —O—S(O)(O)—NH 2 structure. Typically, sulfamate derivatives as used here comprise an organic moiety containing about 1-50 carbon atoms and 0 to about 10 independently selected heteroatoms (e.g., O, S, N, P, Si) linked to a formula 1 steroid nucleus at a variable group such as R 1 -R 6 , R 10 , R 15 , R 17 or R 18 through a suitable structure such as —O—S(O)(O)—NH—, e.g., organic moiety-O—S(O)(O)—NH-steroid, steroid-O—S(O)(O)—NH-organic moiety or steroid-O—S(O)(O)—NH 2 . The organic moiety is as described above for esters.

“Sulfamide” and the like mean a moiety that comprises a —NH—S(O)(O)—NH— or —NH—S(O)(O)—NH 2 structure. Typically, sulfamide moieties comprise an organic moiety containing about 1-50 carbon atoms and 0 to about 10 independently selected heteroatoms (e.g., O, S, N, P, Si) linked to a formula 1 steroid nucleus at a variable group such as R 1 -R 6 , R 10 , R 15 , R 17 or R 18 through a suitable structure such as —NH—S(O)(O)—NH—, e.g., steroid-NH—S(O)(O)—NH-organic moiety, steroid-NH—S(O)(O)—NH 2 , steroid-NH—S(O)(O)—NHR PR or steroid-NH—S(O)(O)—N(R PR ) 2 , where R PR independently or together are a protecting group such as C1-C8 optionally substituted alkyl. The organic moiety is as described above for esters.

“Sulfinamide” and the like mean a moiety that comprises a —C—S(O)—NH— structure. Typically, sulfinamide moieties comprise an organic moiety containing about 1-50 carbon atoms and 0 to about 10 independently selected heteroatoms (e.g., O, S, N, P, Si) linked to a formula 1 steroid nucleus at a variable group such as R 1 -R 6 , R 10 , R 15 , R 17 or R 18 through a suitable structure such as steroid-S(O)—NH-organic moiety, steroid-NH—S(O)-organic moiety, steroid-S(O)—NH 2 , steroid-S(O)—NHR PR moiety or steroid-S(O)—N(R PR ) 2 , where R PR independently or together are a protecting group such as C1-C8 optionally substituted alkyl. The organic moiety is as described above for esters.

“Sulfurous diamide” and the like mean a moiety that comprises a —NH—S(O)—NH— or —NH—S(O)—NH 2 structure. Typically, sulfurous diamide moieties comprise an organic moiety containing about 1-50 carbon atoms and 0 to about 10 independently selected heteroatoms (e.g., O, S, N, P, Si) linked to a formula 1 steroid nucleus at a variable group such as R 1 -R 6 , R 10 , R 15 , R 17 or R 18 through a suitable structure such as —C—NH—S(O)—NH—C— or —CH 2 —NH—S(O)—NH—CH 2 —, e.g., steroid-NH—S(O)—NH-organic moiety, steroid-NH—S(O)—NH 2 , steroid-NH—S(O)—NHR PR or steroid-NH—S(O)—N(R PR ) 2 , where R PR independently or together are a protecting group such as C1-C8 optionally substituted alkyl. The organic moiety is as described above for esters.

“Sulfonate ester”, “sulfonate derivative”, “sulfonate” and the like mean a moiety that comprises a —O—S(O)(O)— or —S(O)(O)—O— structure. Typically, sulfonate derivatives comprise an organic moiety containing about 1-50 carbon atoms and 0 to about 10 independently selected heteroatoms (e.g., O, S, N, P, Si) linked to a formula 1 steroid nucleus at a variable group such as R 1 -R 6 , R 10 , R 15 , R 17 or R 18 through a suitable structure such as —S(O)(O)—O—, e.g., organic moiety-O—S(O)(O)-steroid, HO—S(O)(O)-steroid or organic moiety-S(O)(O)—O-steroid. The organic moiety is as described above for esters.

“Amide”, “amide derivative” and the like mean an organic moiety as described for ester that comprises a —C(O)—NR PR — or —C(O)—NH— moiety, where R PR is —H or a protecting group. In some embodiments, the —C(O)NR PR — group is linked to the steroid nucleus at a variable group such as R 1 -R 6 , R 10 , R 15 , R 17 or R 18 , i.e., organic moiety-C(O)NR PR -steroid, organic moiety-C(O)—NH-steroid or steroid-C(O)NR PR -organic moiety. The organic moiety is as described above for esters.

“Ether” means an organic moiety as described for ester that comprises 1, 2, 3, 4 or more —O— moieties, usually 1 or 2. In some embodiments, the —O— group is linked to the steroid nucleus at a variable group such as R 1 -R 6 , R 10 , R 15 , R 17 or R 18 , e.g., organic moiety-O-steroid. The organic moiety is as described above for esters.

“Thioether” means an organic moiety as described for ester that comprises 1, 2, 3, 4 or more —S— moieties, usually 1 or 2. In some embodiments, the —S— group is linked to the steroid nucleus at a variable group such as R 1 -R 6 , R 10 , R 15 , R 17 or R 18 , e.g., organic moiety-S-steroid, organic moiety-S—CH 2 —S-steroid or organic moiety-S—S-steroid. The organic moiety is as described above for esters.

“Acyl group” or “acyl” means an organic moiety as described for ester that comprises 1, 2, 3, 4 or more —C(O)— groups. In some embodiments, the —C(O)— group is linked to the steroid nucleus at a variable group such as R 1 -R 6 , R 10 , R 15 , R 17 or R 18 , e.g., organic moiety-C(O)-steroid. The organic moiety is as described above for esters. Exemplary acyl moieties include moieties such as —C(O)—N(C1-C6 alkyl) 2 , —C(O)—NH(C1-C6 alkyl), —C(O)—NH—C(CH 3 ) 3 , —C(O)—NH—CH(CH 3 ) 2 , —C(O)—NH—C(CH 3 ) 2 —CH 3 , —C(O)—NH—CH(CH 3 )—CH 3 , —C(O)—NH—C(CH 3 )—CH 2 —CH 3 , —C(O)NH 2 , —C(O)NHR PR , —C(O)—CH 3 , —C(O)—CH 2 —CH 3 , —C(O)—CH 2 —CH 2 —CH 3 , —C(O)—CH 2 OH, —C(O)—CH 2 OR PR , —C(O)—CH 2 —CH 2 H, —C(O)—CH 2 —CH 2 OR PR , —C(O)—CH 2 -halogen, —C(O)—CH 2 —CH 2 -halogen, —C(O)—CH 2 —COOR PR , —C(O)—CH 2 —CH 2 —COOR PR , —C(O)—CH 2 —CH 2 —CHOH, —C(O)—CH 2 —NH 2 , —C(O)—CH 2 —NHR PR , —C(O)—CH 2 —N(R PR ) 2 , —C(O)—CH 2 —NH—(C1-C6 alkyl), —C(O)—CH 2 —N(C1-C6 alkyl) 2 , —C(O)—NH—CH═CH 2 , —C(O)—NH—C≡CH, —C(O)—NH—CH 3 , —C(O)—NH—CN, —C(O)—NH—CH 2 —CN, where each alkyl is the same or different and is optionally independently substituted and each R PR is —H or an independently selected protecting group for the atom or functional group to which it is attached, or two R PR together are a protecting group for the atom or functional group to which they are attached.

“Thioacyl” means an organic moiety as described for ester that comprises 1, 2, 3, 4 or more —C(S)— groups. In some embodiments, the —C(S)— group is linked to the steroid nucleus at a variable group such as R 1 -R 6 , R 10 , R 15 , R 17 or R 18 , e.g., organic moiety-C(S)-steroid. The organic moiety is as described above for esters. Exemplary thioacyl moieties include moieties as described above for the acyl group, except that sulfur replaces the appropriate oxygen atom.

“Carbonate” means an organic moiety as described for ester that comprises 1, 2, 3, 4 or more —O—C(O)—O— structures. Typically, carbonate groups as used here comprise an organic moiety containing about 1-50 carbon atoms and 0 to about 10 independently selected heteroatoms (e.g., O, S, N, P, Si) linked to a formula 1 steroid nucleus at a variable group such as R 1 -R 6 , R 10 , R 15 , R 17 or R 18 through the —O—C(O)—O— structure, e.g., organic moiety-O—C(O)—O-steroid. The organic moiety is as described above for esters.

“Carbamate” means an organic moiety as described for ester that comprises 1, 2, 3, 4 or more —O—C(O)NR PR — structures where R PR is —H, a protecting group or an organic moiety as described for ester. Typically, carbamate groups as used here comprise an organic moiety containing about 1-50 carbon atoms and 0 to about 10 independently selected heteroatoms (e.g., O, S, N, P, Si) linked to a formula 1 steroid nucleus at a variable group such as R 1 -R 6 , R 10 , R 15 , R 17 or R 18 through the —O—C(O)—NR PR — structure, e.g., organic moiety-O—C(O)—NR PR -steroid or steroid-O—C(O)—NR PR -organic moiety. The organic moiety is as described above for esters.

As used herein, “monosaccharide” means a polyhydroxy aldehyde or ketone having the empirical formula (CH 2 O) n where n is 3, 4, 5, 6 or 7. Monosaccharide includes open chain and closed chain forms, but will usually be closed chain forms. Monosaccharide includes hexofuranose and pentofuranose sugars such as 2′-deoxyribose, ribose, arabinose, xylose, their 2′-deoxy and 3′-deoxy derivatives and their 2′,3′-dideoxy derivatives. Monosaccharide also includes the 2′,3′ dideoxydidehydro derivative of ribose. Monosaccharides include the D-, L- and DL-isomers of glucose, fructose, mannose, idose, galactose, allose, gulose, altrose, talose, fucose, erythrose, threose, lyxose, erythrulose, ribulose, xylulose, ribose, arabinose, xylose, psicose, sorbose, tagatose, glyceraldehyde, dihydroxyacetone and their monodeoxy or other derivatives such as rhamnose and glucuronic acid or a salt of glucuronic acid. Monosaccharides are optionally protected or partially protected. Exemplary monosaccharides include

where R 37 independently is hydrogen, a protecting group, acetamido (—NH—Ac), optionally substituted alkyl such as methyl or ethyl, or an ester such as acetate or proprionate, R 33 is hydrogen, hydroxyl, —NH 2 , —NHR PR , optionally substituted alkyl such as methyl or ethyl, or a cation such as NH 4 + , Na + or K + and R 39 is hydrogen, hydroxyl, acetate, proprionate, optionally substituted alkyl such as methyl, ethyl, methoxy or ethoxy.

Optionally substituted alkyl group, optionally substituted alkenyl group, optionally substituted alkynyl group, optionally substituted aryl moiety and optionally substituted heterocycle mean an alkyl, alkenyl, alkynyl, aryl or heterocycle moiety that contains an optional substitution(s). Such moieties include C 1-20 alkyl moieties, C 2-20 alkenyl moieties, C 2-20 alkynyl moieties, aryl moieties, C 2-9 heterocycles or substituted derivatives of any of these.

Optionally substituted “monosaccharide” comprise any C3-C7 sugar, D-, L- or DL-configurations, e.g., erythrose, glycerol, ribose, deoxyribose, arabinose, glucose, mannose, galactose, fucose, mannose, glucosamine, N-acetylneuraminic acid, N-acetylglucosamine, N-acetylgalactosamine that is optionally substituted at one or more hydroxyl groups or hydrogen or carbon atoms. Suitable substitutions are as described above for substituted alkyl moieties and include independently selected hydrogen, hydroxyl, protected hydroxyl, carboxyl, azido, cyano, —O—C 1-6 alkyl, —S—C 1-6 alkyl, —O—C 2-6 alkenyl, —S—C 2-6 alkenyl, ester, e.g., acetate or proprionate, optionally protected amine, optionally protected carboxyl, halogen, thiol or protected thiol. The linkage between the monosaccharide and the steroid is α or β.

Optionally substituted “oligosaccharide” comprises two, three, four or more of any C3-C7 sugars that are covalently linked to each other. The linked sugars may have D-, L- or DL-configurations. Suitable sugars and substitutions are as described for monosaccharides. The linkage between the oligosaccharide and the steroid is α or β, as are the linkages between the monosaccharides that comprise the oligosaccharide. Adjacent monosaccharides may be linked by, e.g., 1→2, 1→3, 1→4, and/or 1→6 glycosidic bonds.

Nucleoside includes 3TC, AZT, D4T, ddI, ddC, G, A, U, C, T, dG, dA, dT and dC.

Polymer includes biocompatible organic polymers, e.g., polyethyleneglycols (“PEGs”) and polyhydroxyalkyl polymers. PEG means an ethylene glycol polymer that contains about 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 or more linked monomers, e.g., about 50-1000 linked monomers. Average molecular weights typically are about 80, 100, 200, 300, 400 or 500, and mixtures thereof may are included, e.g., PEG100 and PEG200, PEG200 and PEG300, PEG100 and PEG300 or PEG200 and PEG400.

As used herein, position numbers that are given for the F1Cs use the numbering convention for cholesterol.

Spiro ring substituents are cyclic structures that are usually 3, 4, 5, 6, 7 or 8 membered rings, e.g., they include 3, 4-, 5-, 6-, 7- or 8-sided rings. In some embodiments, spiro structures share a carbon atom that is present in the steroid ring system, e.g., at the 2, 3, 7, 11, 15, 16 or 17 positions of the F1Cs. Spiro structures include, acetals, thioacetals and lactone rings or cyclic esters. Spirolactones, spiro ring compounds and dihydroxy F1Cs containing cyclic diol groups include F1Cs having the structures

where X is —C(R 10 ) 2 — or —CHR 10 —, and R 10 are independently selected. In some of these embodiments, the R 10 , R 10A , R 10B , R 10C and R 10D variable groups are in the α- or β-configuration and are independently selected from —H, —F, —Cl, —Br, —OH, —OCH 3 , —OC 2 H 5 , an optionally substituted ester such as acetate or propionate, an optionally substituted alkyl such as methyl or ethyl or an amino acid.

As used herein, “innate immunity” refers to one or more components typically associated with nonspecific immune defense mechanisms in a subject. These components include the alternate complement pathway, e.g., Factor B, Factor D and properdin; NK cells, phagocytes (monocytes, macrophages), neutrophils, eosinophils, dendritic cells, fibrocytes; anti-microbial chemicals, e.g., one or more of defensins; physical barriers—skin, mucosal epithelium; or certain interleukins, chemokines, cytokines, lung or alveolar macrophage respiratory burst activity or a lung surfactant protein such as surfactant protein A or surfactant protein D. Innate immunity plays a role in resistance to intracellular parasite infections, e.g., white blood cell infection, a liver infection, and other infections, e.g., lymph node infections. Detectable enhancement of innate immunity mechanism by F1Cs or method described herein can also enhance phagolysosome fusion or movement, which some pathogens, e.g., intracellular bacteria such as mycobacteria, or Listeria inhibit.

Terms such as “immune dysregulation”, “immune dysregulation condition”, “unwanted immune response” and the like mean that a subject has or is subject to developing an immune response that is not desirable or is suboptimal for the subject's condition. Such dysregulation or unwanted responses can arise from various clinical conditions or diseases or as a result of treatment of such conditions or diseases, e.g., inflammation, autoimmunity, organ or tissue transplant rejection (e.g., allograft, xenograft), infections, cancers, chemotherapy treatments, trauma, allergy conditions or in conditions where a subject mounts a Th1, Tc1, Th2 or Tc2 immune response that is considered to be pathogenic, ineffective, insufficient or suboptimal. Immune dysregulation conditions are as described herein or in the cited references.

Terms such as “cellular response”, “cellular activity”, “biological response”, “biological activity” and the like mean a response or activity that is detectably modulated in response to the presence of a F1C. Such responses or activities can be direct effects or indirect effects on one or more cellular activities or on the expression or level of one or more molecules that the affected cell(s) bind, sequester, synthesize or respond to. Such responses or activities include a detectable change in the synthesis or level of one or more cytokines, growth factors, transcription factors (including receptors and their cofactors), enzymes, Th1- or Th2-associated antibody subtype responses or the like. Typically, the cytokines, growth factors, transcription factors, enzymes or antibodies that are modulated are involved in the amelioration of a pathological condition or in the establishment, maintenance, severity or progression of a pathological condition.

As used herein, references to CD molecules, specific immune cell subsets, immune responses and the like, generally use nomenclature that applies to molecules, cells or the like that are found in humans. Analogs or counterparts of such molecules, cells or the like in other species may have a differing nomenclature, but are included in this invention. A description of the nomenclature and function of various CD molecules and immune cell subsets are as found in the scientific literature. References to Th0, Th1 or Th2 cells and references to Th1 or Th2 immune responses in the context of human patients refers to the human counterparts of the murine Th0, Th1 or Th2 immune cells or responses. For reviews see, e.g., A. K. Abbas et al., editors, Cellular and Molecular Immunology , W.B. Saunders Company, third edition, 1997, ISBN 0-7216-4024-9, pages 4-469, and I. Kimber and M. K. Selgrade, editors, T Lymphocyte Subpopulations in Immunotoxicology , John Wiley & Sons Ltd., 1998, ISBN 0-471-97194-4, pages 1-53.

“Immunosuppressive molecule” means molecules such as cyclosporin, cyclohexamide, mitomycin C, adriamycin, taxol and amphotericin B. These molecules tend to have toxicities toward the immune system and are directly or indirectly immunosuppressive, e.g., they are toxic to dividing cells, they inhibit proliferation of immune cell precursors or they can downregulate an otherwise desired or improved immune response or condition.

“Nuclear hormone receptor” means a gene product, typically as a protein monomer or dimer that can bind to a ligand and affect transcription of one or more genes. Ligands include, e.g., certain natural steroids, steroid analogs, F1Cs or another ligand such as a lipid, e.g., a prostaglandin, or the like. Nuclear hormone receptors include orphan steroid receptors, which typically function as heterodimers and the classical steroid receptors, e.g., androgen receptor (“AR”), estrogen receptor α (“ERα”), estrogen receptor β (“ERβ”), that function as homodimers. Nuclear hormone receptors include species that form heterodimers, e.g., VDR-RXR or TR-RXR. Nuclear hormone receptors also include isoforms, e.g., PXR.1 and PXR.2 for the PXR receptor, The natural ligand and/or biological function for some orphan steroid receptors is at least partially unknown. Nuclear hormone receptors include the homologs of the receptors, e.g., the homolog of CARβ known as MB67. Isoforms are typically generated by different splicing pathways for a nuclear RNA from one gene, while homologs are typically a distinct copy of a nuclear hormone receptor gene, where the gene copy encodes only relatively small differences compared to the reference nuclear hormone receptor gene product. Such differences are most often found in areas other than the dimerization region and the steroid binding region of the nuclear hormone receptor's structure. Typically isoforms and homologs bind the same or similar ligands as the reference gene product or nuclear hormone receptor. Nuclear hormone receptors may be of human or animal origin, e.g., obtained from cells, tissues or cDNA expression libraries derived from cells or tissues of any primate, rodent (including murine), avian, ovine, bovine, equine, canine, feline, insect species, e.g., Drosophila , nematode, e.g., Caenorhabditis elegans , or any of the species within any group (e.g., Family or Genus) of species mentioned herein or in any reference cited herein. Modulation of nuclear hormone receptors by F1Cs can arise from (1) their direct interaction with the receptor or a cofactor thereof or (2) indirect effects such as (A) detectably increased or decreased synthesis or level of the receptor or (B) generation of a signal or stimulus that leads to detectable modulation of one or more biological activities of the receptor, e.g., detectable inhibition of receptor mediated gene transcription or detectable enhancement of receptor mediated gene transcription.

An “agonist” or an “antagonist” is a compound or composition, usually containing a F1C, that respectively, either detectably increases or decreases the activity of a receptor, an enzyme or another biological molecule, which can lead to increased or decreased transcription or mRNA levels of a regulated gene or to another measurable effect such as altered level of activity of the gene product or protein. The increase or decrease in a receptor's or enzyme's activity will be an increase or a decrease of at least about 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95% or a range about between any two of these values, for one or more measurable activities. Receptors, their accessory factors and associated transcription factors can modulate transcription of their target gene(s) by detectably increasing or decreasing transcription or mRNA levels. Biological activities of receptors may also include modulating biological responses such as signal transduction within a cell or ion flux, e.g., sodium, potassium or calcium, across cell or organelle membranes, e.g., across mitochondria.

Terms such as “biologically active metabolite” and the like mean derivatives of the F1Cs that retain a detectable level, e.g., at least about 10%, at least about 20%, at least about 30% or at least about 50%, of at least one desired activity of the parent compound, e.g., antiinflammatory activity or stimulation of a desired immune response. Determination of a desired activity is accomplished essentially as described herein. Such metabolites can be generated in the gastrointestinal tract, in blood or in one or more subject tissues. Such metabolites are detected using standard analytical methods, e.g., GC-MS analysis of an optionally radiolabeled F1C and its metabolites, in blood, urine or other biological samples after it is administered to a subject by one or more routes as disclosed herein. Terms such as “metabolic precursor” of F1Cs and the like can include compounds that generate a detectable level of the F1C or a detectable level, e.g., at least about 10%, at least about 20%, at least about 30% or at least about 50%, of at least one desired activity of the F1C. Determination of a desired activity is accomplished essentially as described herein. Conversion of metabolic precursors can occur in the gastrointestinal tract, in blood or in one or more subject tissues.

“Amino acid” means an amino acid moiety that comprises any naturally-occurring or synthetic amino acid residue, i.e., any moiety comprising at least one carboxyl and at least one amino residue directly linked by one, two three or more carbon atoms, typically one (α) carbon atom. The nature and identity of the intervening structure located between the carboxyl and amino groups can have a variety of structures including those described herein. Typically, amino acids linked to the steroid through the amine group (“N-linked amino acid”) have sufficient conformation and length to be capable of autocatalytic hydrolysis of the amino acid-steroid bond and release of the steroid. This can occur when the free carboxyl is generated in vivo by deesterification, deamidation or peptidolytic cleavage of the precursor containing a linkage between the amino acid's amine group and the steroid. Hydrolysis of the bond between an amino acid's carboxyl or amino group and the steroid can also occur by chemical or enzymatic activity, e.g., esterase cleavage or non-enzymatic hydrolysis.

In general, the amino acids corresponding to the residues employed in the F1Cs are naturally occurring and have no significant pharmacological activity per se. However, optimal pharmacokinetic activity, (substantially complete hydrolysis upon hydrolysis of the distal amide or ester bond) may be achieved by using non-naturally occurring amino acid residues. The intervening structure may be as simple as methylene when the amino acid residue is glycyl, or substituted methylene for other a amino acids. The structure ordinarily contains up to about 5 carbon or heteroatoms in the direct linkage between the amino acid's carboxyl carbon and the amine nitrogen. Thus, amino acids can comprise intervening ethylene, propylene, butylene, or pentylene groups or their substituted analogs, such as for example, oxyesters or ethers in which oxygen replaces carbon and, as appropriate, hydrogen. An example of such an intervening structure would be —CH—O—C(R 22 )(R 23 )—, where R 22 and R 23 are independently selected hydrogen or organic moieties as described above for esters. In some embodiments one of R 22 and R 23 is hydrogen and the other is a C2-20 organic moiety. Typically the organic moieties contain about 1-20 carbon atoms and 0, 1, 2, 3, 4 or 5 independently selected heteroatoms, which are typically selected from oxygen, nitrogen, sulfur and phosphorus. In general, fewer intervening atoms are used when more rapid hydrolysis is desired, although larger structures are suitable if, e.g., they possess sufficient flexibility or have conformations to allow positioning of the carboxyl group in proximity to the amino acid-steroid bond.

Ordinarily, R 22 is —H, methyl or hydroxymethyl, usually —H, and R 23 is a side chain or group of a naturally occurring amino acid. Amino acid side chains include analogs where the side chain is a C 1-15 homolog of the corresponding natural compound, e.g., methylene, ethylene, propylene, butylene or a substituted derivative thereof, e.g., an alkyl, ether or alkoxy (e.g., methoxy, ethoxy, propoxy) substituted derivative. In general, for carboxyl-containing side chains, if the C atom of the side chain carboxyl is linked by 5 or less atoms to the N then the carboxyl optionally will be blocked, e.g. by esterification or amidation wherein the ester or amide bonds are hydrolyzable in vivo. R 22 also is taken together with R 30 to form a proline residue (—CH 2 —) 3 . Thus, R 23 is generally a side group such as —H, —CH 3 , —CH(CH 3 ) 2 , —CH 2 —CH(CH 3 ) 2 , —CHCH 3 —CH 2 —CH 3 , —CH 2 —C 6 H 5 , —CH 2 CH 2 —S—CH 3 , —CH 2 OH, —CH(OH)—CH 3 , —CH 2 —SH, —CH 2 —C 6 H 4 OH, —CH 2 —CO—NH 2 , —CH 2 CH 2 —CO—NH 2 , —CH 2 —COOH, —CH 2 —CH 2 —COOH, —(CH 2 ) 4 —NH 2 and —(CH 2 ) 3 —NH—C(NH 2 )—NH 2 . R 23 also includes 1-guanidinoprop-3-yl, benzyl, 4-hydroxybenzyl, imidazol-4-yl, indol-3-yl, methoxyphenyl and ethoxyphenyl. The optimal R 30 group is readily selected using routine assays.

In general, the amino acid residue has the structure shown in the formulas below. Ordinarily, n is 1 or 2, R 22 is —H and R 23 is a moiety containing one or more of the following groups: amino, carboxyl, amide, carboxyl ester, hydroxyl, C 6 -C 7 aryl, ether (—O—), thioether (—S—), n-, s- or t-alkyl (C 1 -C 6 ), guanidinyl, imidazolyl, indolyl, sulfhydryl, sulfoxide, and phosphoryl. The R 22 and R 23 substituents can have a wide variety of structures including those disclosed herein, e.g., esters, ethers or carbonates.

When the amino acid residues contain one or more chiral centers, any of the D, L, meso, threo or erythro (as appropriate) racemates or mixtures thereof, fall within the scope of this invention. In general, if it is desired to rely on non-enzymatic means of hydrolysis, D isomers should be used. On the other hand, L isomers may be more versatile since they can be susceptible to both non-enzymatic as well as potential targeted enzymatic hydrolysis, and are more efficiently transported by amino acid or dipeptidyl transport systems in the gastrointestinal tract.

Examples of suitable amino acid residues include the following: Glycyl; aminopolycarboxylic acids, e.g., aspartic acid, β-hydroxyaspartic acid, glutamic acid, β-hydroxyglutamic acid, β-methylaspartic acid, β-methylglutamic acid, β,β-dimethylaspartic acid, γ-hydroxyglutamic acid, β,γ-dihydroxyglutamic acid, β-phenylglutamic acid, γ-methyleneglutamic acid, 3-aminoadipic acid, 2-aminopimelic acid, 2-aminosuberic acid and 2-aminosebacic acid residues; amino acid amides such as glutaminyl and asparaginyl; polyamino- or polybasic-monocarboxylic acids such as arginine, lysine, β-aminoalanine, γ-aminobutyrine, ornithine, citruline, homoarginine, homocitrulline, 5-hydroxy-2,6-diaminohexanoic acid (commonly, hydroxylysine, including allohydroxylysine) and diaminobutyric acid residues; other basic amino acid residues such as histidinyl; diaminodicarboxylic acids such as α,α′-diaminosuccinic acid, α,α′-diaminoglutaric acid, α,α′-diaminoadipic acid, α,α′-diaminopimelic acid, α,α′-diamino-β-hydroxypimelic acid, α,α′-diaminosuberic acid, α,α′-diaminoazelaic acid, and α,α′-diaminosebacic acid residues; imino acids such as proline, 4- or 3-hydroxy-2-pyrrolidinecarboxylic acid (commonly, hydroxyproline, including allohydroxyproline), γ-methylproline, pipecolic acid, 5-hydroxypipecolic acid, —N([CH 2 ] n COOR PR ) 2 , wherein n is 1, 2, 3, 4, 5 or 6 and R PR is —H or a protecting group, and azetidine-2-carboxylic acid residues; a mono- or di-alkyl (typically C 1 -C 8 branched or normal) amino acid such as alanine, valine, leucine, allylglycine, butyrine, norvaline, norleucine, heptyline, α-methylserine, α-amino-α-methyl-γ-hydroxyvaleric acid, α-amino-α-methyl-δ-hydroxyvaleric acid, α-amino-α-methyl-ε-hydroxycaproic acid, isovaline, α-methylglutamic acid, α-aminoisobutyric acid, α-aminodiethylacetic acid, α-aminodiisopropylacetic acid, α-aminodi-n-propylacetic acid, α-aminodiisobutylacetic acid, α-aminodi-n-butylacetic acid, α-aminoethylisopropylacetic acid, α-amino-n-propylacetic acid, α-aminodiisoamyacetic acid, α-methylaspartic acid, α-methylglutamic acid, 1-aminocyclopropane-1-carboxylic acid; isoleucine, alloisoleucine, tert-leucine, β-methyltryptophan and α-amino-β-ethyl-β-phenylpropionic acid residues; β-phenylserinyl; aliphatic α-amino-β-hydroxy acids such as serine, β-hydroxyleucine, β-hydroxynorleucine, β-hydroxynorvaline, and α-amino-β-hydroxystearic acid residues; α-Amino, α-, γ-, δ- or ε-hydroxy acids such as homoserine, γ-hydroxynorvaline, δ-hydroxynorvaline and epsilon-hydroxynorleucine residues; canavinyl and canalinyl; γ-hydroxyornithinyl; 2-Hexosaminic acids such as D-glucosaminic acid or D-galactosaminic acid residues; α-amino-β-thiols such as penicillamine, β-thiolnorvaline or β-thiolbutyrine residues; other sulfur containing amino acid residues including cysteine; homocystine; β-phenylmethionine; methionine; S-allyl-L-cysteine sulfoxide; 2-thiolhistidine; cystathionine; and thiol ethers of cysteine or homocysteine; phenylalanine, tryptophan and ring-substituted a amino acids such as the phenyl- or cyclohexylamino acids α-aminophenylacetic acid, α-aminocyclohexylacetic acid and α-amino-β-cyclohexylpropionic acid; phenylalanine analogues and derivatives comprising aryl, lower alkyl, hydroxy, guanidino, oxyalkylether, nitro, sulfur or halo-substituted phenyl (e.g., tyrosine, methyltyrosine and o-chloro-, p-chloro-, 3,4-dichloro, o-, m- or p-methyl-, 2,4,6-trimethyl-, 2-ethoxy-5-nitro, 2-hydroxy-5-nitro and p-nitro-phenylalanine); furyl-, thienyl-, pyridyl-, pyrimidinyl-, purine or naphthylalanines; and tryptophan analogues and derivatives including kynurenine, 3-hydroxykynurenine, 2-hydroxytryptophan and 4-carboxytryptophan residues; α-amino substituted amino acid residues including sarcosine (N-methylglycine), N-benzylglycine, N-methylalanine, N-benzylalanine, N-methylphenylalanine, N-benzylphenylalanine, N-methylvaline and N-benzylvaline; and α-Hydroxy and substituted α-hydroxy amino acid residues including serine, threonine, allothreonine, phosphoserine and phosphothreonine residues.

Any one of the foregoing or other known amino acids are suitably employed in this invention. Typically, amino acids are capable of autocatalytically hydrolyzing the amino acid-steroid bond. Thus, they typically contain, or upon being hydrolyzed in vivo, contain a free carboxyl group or amine group.

Also of interest are hydrophobic amino acids such as mono- or di-alkyl or aryl amino acids, cycloalkylamino acids and the like. These residues, together with R 29 -R 34 (R 31 -R 34 are defined below) can contribute to cell permeability by modulating the lipophilicity of a F1C. Typically, the residue does not contain a sulfhydryl or guanidino substituent.

Peptide means 2, 3 or more of the two or more amino acids as defined above are bonded together, usually by an amide bond or normal peptide bond. Variable groups in the F1Cs such as R 1 -R 10 can comprise a peptide. Typically the amino acids are linked through normal peptide bonds, e.g., —CO—NH—, between adjacent amino acid residues. Peptides comprise dipeptides (dimers), tripeptides (trimers), short peptides of 4, 5, 6, 8, 10 or 15 residues, and longer peptides or proteins having about 100 or more residues. F1Cs that comprise a peptide can be used as immunogens, prodrugs or as synthetic precursors for other steroid derivatives. In one embodiment, the peptide will contain a peptidolytic enzyme cleavage site at the peptide bond linking the first residue and the next residue distal to the steroid residue. Such cleavage sites are optionally flanked by enzymatic recognition structures, e.g. particular residues recognized by a hydrolytic enzyme, e.g., a peptidase located in the serum or in cells.

Peptidolytic enzymes are well known, and in particular include carboxypeptidases. Carboxypeptidases digest polypeptides by removing C-terminal residues, and are specific in many instances for particular C-terminal sequences. Such enzymes and their substrate requirements in general are well known. For example, a dipeptide having a given pair of residues and a free carboxyl terminus is covalently bonded through its α-amino group to the steroid nucleus. It is expected that the peptide will be cleaved by the appropriate dipeptidase, protease or by chemical hydrolysis, leaving the carboxyl of the proximal amino acid residue to autocatalytically cleave the amidate bond.

Examples of suitable dipeptidyl groups (designated by their single letter symbols) are shown in the table below. The single letter designations are: Y tyrosine, G glycine, F phenylalanine, M methionine, A alanine, S serine, I isoleucine, L leucine, T threonine, V valine, P praline, L lysine, H histidine, Q glutamine, E glutamic acid, W tryptophan, R arginine, D aspartic acid, N asparagine and C cysteine.

Dipeptides

AA, AR, AN, AD, AC, AE, AQ, AG, AH, AI, AL, AK, AM, AF, AP, AS, AT, AW, AY, AV, RA,

RR, RN, RD, RC, RE, RQ, RG, RH, RI, RL, RK, RM, RF, RP, RS, RT, RW, RY, RV, NA,

NR, NN, ND, NC, NE, NQ, NG, NH, NI, NL, NK, NM, NF, NP, NS, NT, NW, NY, NV, DA,

DR, DN, DD, DC, DE, DQ, DG, DH, DI, DL, DK, DM, DF, DP, DS, DT, DW, DY, DV, CA,

CR, CN, CD, CC, CE, CQ, CG, CH, CI, CL, CK, CM, CF, CP, CS, CT, CW, CY, CV, EA,

ER, EN, ED, EC, EE, EQ, EG, EH, EI, EL, EK, EM, EF, EP, ES, ET, EW, EY, EV, QA, QR,

QN, QD, QC, QE, QQ, QG, QH, QI, QL, QK, QM, QF, QP, QS, QT, QW, QY, QV, GA, GR,

GN, GD, GC, GE, GQ, GG, GH, GI, GL, GK, GM, GF, GP, GS, GT, GW, GY, GV, HA, HR,

HN, HD, HC, HE, HQ, HG, HH, HI, HL, HK, HM, HF, HP, HS, HT, HW, HY, HV, IA, IR, IN,

ID, IC, IE, IQ, IG, IH, II, IL, IK, IM, IF, IP, IS, IT, IW, IY, IV, LA, LR, LN, LD, LC, LE, LQ,

LG, LH, LI, LL, LK, LM, LF, LP, LS, LT, LW, LY, LV, KA, KR, KN, KD, KC, KE, KQ, KG,

KH, KI, KL, KK, KM, KF, KP, KS, KT, KW, KY, KV, MA, MR, MN, MD, MC, ME, MQ, MG,

MH, MI, ML, MK, MM, MF, MP, MS, MT, MW, MY, MV, FA, FR, FN, FD, FC, FE, FQ, FG,

FH, FI, FL, FK, FM, FF, FP, FS, FT, FW, FY, FV, PA, PR, PN, PD, PC, PE, PQ, PG, PH,

PI, PL, PK, PM, PF, PP, PS, PT, PW, PY, PV, SA, SR, SN, SD, SC, SE, SQ, SG, SH, SI,

SL, SK, SM, SF, SP, SS, ST, SW, SY, SV, TA, TR, TN, TD, TC, TE, TQ, TG, TH, TI, TL,

TK, TM, TF, TP, TS, TT, TW, TY, TV, WA, WR, WN, WD, WC, WE, WQ, WG, WH, WI,

WL, WK, WM, WF, WP, WS, WT, WW, WY, WV, YA, YR, YN, YD, YC, YE, YQ, YG, YH,

YI, YL, YK, YM, YF, YP, YS, YT, YW, YY, YV, VA, VR, VN, VD, VC, VE, VQ, VG, VH, VI,

Such dipeptides include species where both amino acids are in the L configuration, the D configuration or mixtures of configurations.

Tripeptides, i.e., 3 linked amino acid residues, are also useful embodiments. Each amino acid in a tripeptide may be in an L, D or mixed configuration. Tripeptides include those where A, C, D, E, F, G, H, I, K, L, M, N, P, Q, R, S, T, V, W or Y is linked by a standard peptide bond to the amino or the carboxyl terminus of any of the dipeptides listed above. The sequence —X1-pro-X2-(where X1 is any amino acid and X2 is hydrogen, any amino acid residue or a carboxyl ester of proline) will be cleaved by luminal carboxypeptidase to yield X1 with a free carboxyl, which in turn autocatalytically cleaves the amidate bond. X2 usually will be a benzyl ester of the carboxy group of X2. Other embodiments include tetrapeptides such as ones where any two of the dipeptides listed above, which may be the same or different dipeptides (e.g., AA and AA linked together or, e.g., AA and GI linked together), are linked to each other by a peptide bond through the amino terminus or carboxyl terminus. One, 2 or more tetrapeptides may bonded to the formula 1 or formula 2 compound through the tetrapeptide's amino or carboxyl terminus.

In some embodiments, the formula 1 or formula 2 compound comprises one or more amino acids or peptides having the structure (A), (B) or (C): (A) R 32 —NH—{[C(R 29 )(R 30 )] b —C(O)—N(R 31 )} f —[C(R 29 )(R 30 )] a —C(O)—O-steroid; (B) R 33 —O—{C(O)—[C(R 29 )(R 30 )] d —N(R 31 )} g —C(O)—[C(R 29 )(R 30 )] c —N(R 31 )—O-steroid; or (C)R 33 —O—{C(O)—[C(R 29 )(R 30 )] d —N(R 31 )} e —C(O)—[C(R 29 )(R 30 )] c —N(R 31 )—C(O)—O-steroid, wherein (A), (B) or (C) are independently selected and they are bonded to 1, 2, 3 or more of R 1 through R 4 , where each R 29 -R 31 is independently selected; R 29 independently are —H or a C1-C20 organic moiety (e.g., C 1-6 alkyl, e.g. —CH 3 or —C 2 H 5 ); R 30 independently are the side chain of an amino acid, including the side chain of naturally occurring amino acids as described above, e.g., —H, —CH 3 , —CH 2 C 6 H 5 ; R 31 is —H or a protecting group; R 32 and R 33 independently comprise —H, a protecting group, an ester or an amide where each atom or group is independently chosen; a, b, c and d independently are 1, 2, 3, 4 or 5, usually 1; e, f and g independently are an integer from 0 to about 1000, typically they independently are 0, 1, 2, 3, 4, 5, 6, 7 or 8; a, b, c and d independently are 1 or 2; e, f and g independently are 0, 1, 2, 3, 4 or 5.

If the amino acid(s) or residue(s) has 2 or more amine groups, e.g., a lysinyl or arginyl, or ornithinyl residue, then R 29 is usually —H and R 30 may comprise −[C(R 34 ) 2 ] n2 N(R PR )— where n2 is 0, 1, 2, 3, 4, 5 or 6, R PR is —H or a protecting group and each R 34 independently is —H, C 1 -C 20 optionally substituted alkyl, C 6 -C 20 optionally substituted aryl, C 7 -C 20 optionally substituted alkylaryl, C 7 -C 20 optionally substituted arylalkyl, C 1 -C 20 optionally substituted alkoxy, C 6 -C 20 optionally substituted aryloxy or hydroxyl. Such compounds will contain a plurality of steroid moieties. For example when both the epsilon (ε) or delta (δ) and alpha (α) amino groups of lysine or ornithine are substituted with steroid moieties the amidate is believed to be capable of releasing two molecules of active drug, each expected to emerge under different pharmacokinetics and therefore further sustaining the drug release.

Salts of F1Cs. Invention embodiments include salts and complexes of F1Cs, including pharmaceutically acceptable or salts that are relatively non-toxic. Some of the F1Cs have one or more moieties that carry at least a partial positive or negative charge in aqueous solutions, typically at a pH of about 4-10, that can participate in forming a salt, a complex, a composition with partial salt and partial complex properties or other noncovalent interactions, all of which we refer to as a “salt(s)”. Salts are usually biologically compatible or pharmaceutically acceptable or non-toxic, particularly for mammalian cells. Salts that are biologically toxic are optionally used with synthetic intermediates of F1Cs. When a water-soluble composition is desired, monovalent salts are usually used.

Metal salts typically are prepared by reacting the metal hydroxide with a compound of this invention. Examples of metal salts that are optionally prepared in this way are salts containing Li + , Na + , and K + . A less soluble metal salt can be precipitated from the solution of a more soluble salt by adding a suitable metal compound. Invention salts may be formed from acid addition of certain organic acids, such as organic carboxylic acids, and inorganic acids, such as alkylsulfonic acids or hydrogen halide acids, to acidic or basic centers on F1Cs, such as basic centers on the invention pyrimidine base analogs. Metal salts include ones containing Na + , Li + , K + , Ca ++ or Mg ++ . Other metal salts may contain aluminum, barium, strontium, cadmium, bismuth, arsenic or zinc ion.

Salt(s) of F1Cs may comprise a combination of appropriate cations such as alkali and alkaline earth metal ions or ammonium and quaternary ammonium ions with the acid anion moiety of the phosphoric acid or phosphonic acid group, which may be present in polymers or monomers.

Salts are produced by standard methods, including dissolving free base in an aqueous, aqueous-alcohol or aqueous-organic solution containing the selected acid, optionally followed by evaporating the solution. The free base is reacted in an organic solution containing the acid, in which case the salt usually separates directly or one can concentrate the solution.

Suitable amine salts include amines having sufficient basicity to form a stable salt, usually amines of low toxicity including trialkyl amines (tripropylamine, triethylamine, trimethylamine), procaine, dibenzylamine, N-benzyl-betaphenethylamine, ephenamine, N,N′-dibenzylethylenediamine, N-ethylpiperidine, benzylamine and dicyclohexylamine.

Salts include organic sulfonic acid or organic carboxylic acid salts, made for example by addition of the acids to basic centers, typically amines. Exemplary sulfonic acids include C 6-16 aryl sulfonic acids, C 6-16 heteroaryl sulfonic acids and C 1-16 alkyl sulfonic acids such as phenyl sulfonic acid, a-naphthalene sulfonic acid, β-naphthalene sulfonic acid, (S)-camphorsulfonic acid, methyl (CH 3 SO 3 H), ethyl (C 2 H 5 SO 3 H), n-propyl, i-propyl, n-butyl, s-butyl, i-butyl, t-butyl, pentyl and hexyl sulfonic acids. Exemplary organic carboxylic and other acids include C 1-16 alkyl, C 6-16 aryl carboxylic acids and C 4-16 heteroaryl carboxylic acids such as acetic, glycolic, lactic, pyruvic, malonic, glutaric, tartaric, citric, fumaric, succinic, malic, maleic, oxalic, hydroxymaleic, benzoic, hydroxybenzoic, phenylacetic, cinnamic, salicylic, nicotinic, 2-phenoxybenzoic, methanesulfonic, pamoic, propionic, toluenesulfonic and trifluoroacetic acids.

Invention salts include those made from inorganic acids, e.g., HF, HCl, HBr, HI, H 2 SO 4 , H 3 PO 4 , Na 2 CO 3 , K 2 CO 3 , CaCO 3 , MgCO 3 and NaClO 3 . Suitable anions, which are optionally present with a cation such a Ca ++ , Mg ++ , Li + , Na + or K + , include arsenate, arsenite formate, sorbate, chlorate, perchlorate, periodate, dichromate, glycodeoxycholate, cholate, deoxycholate, desoxycholate, taurocholate, taurodeoxycholate, taurolithocholate, tetraborate, nitrate, nitrite, sulfite, sulfamate, hyposulfite, bisulfite, metabisulfite, thiosulfate, thiocyanate, silicate, metasilicate, CN − , gluconate, gulcuronate, hippurate, picrate, hydrosulfite, hexafluorophosphate, hypochlorite, hypochlorate, borate, metaborate, tungstate and urate.

Salts also include the F1C salts with one or more amino acids. Many amino acids are suitable, especially the naturally-occurring amino acids found as protein components, although the amino acid typically is one bearing a side chain with a basic or acidic group, e.g., lysine, arginine, histidine or glutamic acid, or a neutral group such as glycine, serine, threonine, alanine, isoleucine, or leucine.

The invention compositions include F1Cs, their hydrates and the compounds in their ionized, un-ionized, as well as zwitterionic form. Thus, for any F1Cs or compounds described herein with any substituent that contains a moiety that is partially or completely ionizable, e.g., a carboxyl group, the ionizable atom, usually hydrogen, may be replaced with one or more suitable counter ions such as a monovalent metal, a multivalent metal, an alkaline metal, or an ionizable organic moiety, e.g., Li + , Na + , K + , Ca +2 , Mg +2 , SO 4 −2 , PO 4 −2 , CH 3 C(O)O − , CF 3 C(O)O − , F − , Cl − , Br − , I − , NH 4 + , N + (CH 3 ) 4 , N + (C 2 H 5 ) 4 , HN + (C 2 H 5 ) 3 , H 2 N + (C 2 H 5 ) 2 , β-hydroxyethyltrimethylammonium, piperazinium, pyridinium, N-methylpyridinium, morpholimium, N,N-dimethylmorpholinium, p-toluidinium or another ionizable moiety described herein. When a F1C is under conditions, e.g., in a solution, where such moieties can partially or completely ionize, the ionizable moiety may be partially or completely charged, e.g., —C(O)—O − , —NH 3 + , —C(O)—NH 3 + or —O—S(O)(O)—O − may be partially for fully ionized.

Stereoisomers. The F1Cs include enriched or resolved optical isomers at any or all asymmetric atoms as are apparent from the depictions or are included in the compound structures. Both racemic and diasteromeric mixtures, as well as the individual optical isomers can be isolated or synthesized so as to be substantially free of their enantiomeric or diastereomeric partners, and these are all within the scope of the invention. Chiral centers may be found in F1Cs at, for example, one or more of R 1 , R 2 , R 3 , R 4 or R 10 .

One or more of the following methods are used to prepare the enantiomerically enriched or pure isomers herein. The methods are listed in approximately their order of preference, i.e., one ordinarily should employ stereospecific synthesis from chiral precursors before chromatographic resolution before spontaneous crystallization.

Stereospecific synthesis is described in the examples. Methods of this type conveniently are used when the appropriate chiral starting material is available and reaction steps are chosen do not result in undesired racemization at chiral sites. One advantage of stereospecific synthesis is that it does not produce undesired enantiomers that must be removed from the final product, thereby lowering overall synthetic yield. In general, those skilled in the art would understand what starting materials and reaction conditions should be used to obtain the desired enantiomerically enriched or pure isomers by stereospecific synthesis.

If a suitable stereospecific synthesis cannot be empirically designed or determined with routine experimentation then those skilled in the art would turn to other methods. One method of general utility is chromatographic resolution of enantiomers on chiral chromatography resins. These resins are packed in columns, commonly called Pirkle columns, and are commercially available. The columns contain a chiral stationary phase. The racemate is placed in solution and loaded onto the column, and thereafter separated by HPLC. See for example, Proceedings Chromatographic Society—International Symposium on Chiral Separations, Sep. 3-4, 1987. Examples of chiral columns that could be used to screen for the optimal separation technique would include Diacel Chriacel OD, Regis Pirkle Covalent D-phenylglycine, Regis Pirkle Type 1A, Astec Cyclobond II, Astec Cyclobond III, Serva Chiral D-DL=Daltosil 100, Bakerbond DNBLeu, Sumipax OA-1000, Merck Cellulose Triacetate column, Astec Cyclobond I-Beta, or Regis Pirkle Covalent D-Naphthylalanine. Not all of these columns are likely to be effective with every racemic mixture. However, those skilled in the art understand that a certain amount of routine screening may be required to identify the most effective stationary phase. When using such columns it is desirable to employ embodiments of the compounds of this invention in which the charges are not neutralized, e.g., where acidic functionalities such as carboxyl are not esterified or amidated.

Another method entails converting the enantiomers in the mixture to diasteriomers with chiral auxiliaries and then separating the conjugates by ordinary column chromatography. This is a very suitable method, particularly when the embodiment contains free carboxyl, amino or hydroxyl that will form a salt or covalent bond to a chiral auxiliary. Chirally pure amino acids, organic acids or organosulfonic acids are all worthwhile exploring as chiral auxiliaries, all of which are well known in the art. Salts with such auxiliaries can be formed, or they can be covalently (but reversibly) bonded to the functional group. For example, pure D or L amino acids can be used to amidate the carboxyl group of invention embodiments that comprise a carboxyl group and then separated by chromatography.

Enzymatic resolution is another method of potential value. In such methods one prepares covalent derivatives of the enantiomers in the racemic mixture, generally lower alkyl esters (for example of carboxyl), and then exposes the derivative to enzymatic cleavage, generally hydrolysis. For this method to be successful an enzyme must be chosen that is capable of stereospecific cleavage, so it is frequently necessary to routinely screen several enzymes. If esters are to be cleaved, then one selects a group of esterases, phosphatases, and lipases and determines their activity on the derivative. Typical esterases are from liver, pancreas or other animal organs, and include porcine liver esterase.

If the enantiomeric mixture separates from solution or a melt as a conglomerate, i.e., a mixture of enantiomerically pure crystals, then the crystals can be mechanically separated, thereby producing the enantiomerically enriched preparation. This method, however, is not practical for large-scale preparations and is of limited value for true racemic compounds. Asymmetric synthesis is another technique for achieving enantiomeric enrichment. For example, a chiral protecting group is reacted with the group to be protected and the reaction mixture allowed to equilibrate. If the reaction is enantiomerically specific then the product will be enriched in that enantiomer.

Embodiments of formula 1 compounds. For formula 1 compounds (“F1Cs”), 2, 3 or more of R 1 , R 2 , R 3 and R 4 are usually not —H, and typically one or both R 1 and R 4 , R 3 and R 4 , R 2 , R 3 and R 4 or R 2 and R 4 are not —H, and/or 1 or 2 of R 10A , R 10B , R 10C and R 10D are optionally not —H. For any F1C disclosed herein, steroid nucleus carbon atoms that contain two variable groups (e.g., two R 10 at R 8 or R 9 or two R 3 or R 4 at the 16- or 17-position), each variable group is independently selected and each can thus be the same or different, e.g., both can be methyl, ethyl, methoxy, ethoxy, —F, —Cl, —Br, —I, or they can be different. As is apparent from the F1C structures, a double bond can be present at either the 4-5 position or at the 5-6 position, but not at both positions at the same time. Steroid nucleus carbon atoms refers generally to the carbons that make up the rings in F1Cs and carbons, if present, that are bonded to the 10, 13 and 17 positions. Additional carbons that may be at the 17-position are typically numbered using the cholesterol numbering system, although any other suitable nomenclature can be used to describe species or genera of F1C. Exemplary F1C embodiments are described below.

F1Cs include 16α-bromoepiandrosterone (“BrEA”) hemihydrate

which has previously been described, e.g., WO 00/56757. BrEA hemihydrate is used as a F1C either as a pure compound or substantially free of other forms of BrEA, such as amorphous BrEA or anhydrous BrEA.

F1Cs include compounds having the structure 5, 6, 7, 8, 9 and 10,

or a metabolic precursor, a metabolite or salt thereof, wherein

each R 1 , R 2 , R 3 , R 4 , R 10 at the 2, 11 and 15 positions, R 10A , R 10B , R 10C and R 10D independently are —H, —OH, —OR PR , —SR PR , —N(R PR ) 2 , —O—Si—(R 13 ) 3 , —CHO, —CHS, —CN, —SCN, —NO 2 , —ONO 2 , —N 3 , —NH 2 , —COOH, —OSO 3 H, —OPO 3 H, ═O, ═S, ═NOH, ═CH 2 , ═CH 2 CH 3 , ═N—NH—C(═NH)—N(R PR ) 2 , ═N—NH—C(═NH)—NH 2 , an ester, a thioester, a thionoester, a phosphoester, a phosphothioester, a phosphonoester, a phosphiniester, a sulfite ester, a sulfate ester, a sulfoxide, a sulfamate, a sulfonate, a sulfamide, a sulfinamide, a sulfurous diamide, an amide, an amino acid, a peptide, an ether, a thioether, an acyl group, a thioacyl group, a carbonate, a carbamate, a halogen, an acetal, a thioacetal a spiro ring, an optionally substituted alkyl group, an optionally substituted alkenyl group, an optionally substituted alkynyl group, an optionally substituted aryl moiety, an optionally substituted heteroaryl moiety, an optionally substituted heterocycle, an optionally substituted monosaccharide, an optionally substituted oligosaccharide, a nucleoside, a nucleotide, an oligonucleotide, a polymer, or, one or more of two adjacent R 1 -R 4 , R 10 , R 10A , R 10B , R 10C and R 10D are an independently selected epoxide or cyclopropyl ring;

R 5 , R 6 and R 10 at the 5 (if present), 8, 9 and 14 positions independently are —H, —CH 3 , —C 2 H 5 , —OH, —OR PR , —SR PR , —N(R PR ) 2 , —O—Si—(R 13 ) 3 , —CHO, —CHS, —CN, —SCN, —N 3 , —COOH, —OS(O)(O)OH, an ester, a thioester, a thionoester, a sulfite ester, a sulfate ester, a sulfoxide, a sulfamate, a sulfonate, a sulfamide, a sulfinamide, a sulfurous diamide, an amide, an amino acid, a peptide, an ether, a thioether, an acyl group, a thioacyl group, a carbonate, a carbamate, a halogen, an optionally substituted alkyl group, an optionally substituted alkenyl group, an optionally substituted alkynyl group, an optionally substituted aryl moiety, an optionally substituted heteroaryl moiety, an optionally substituted heterocycle, an optionally substituted monosaccharide, an optionally substituted oligosaccharide, or, one, two or more of R 5 , R 6 and R 10 at the 5, 8, 9 and 14 positions, together with a carbon atom that is adjacent to the carbon to which the R 5 , R 6 or R 10 at the 5, 8, 9 or 14 position is bonded are an independently selected epoxide or cyclopropyl ring;

R 7 is —C(R 10 ) 2 —, —C(R 10 ) 2 —C(R 10 ) 2 —, —C(R 10 ) 2 —C(R 10 ) 2 —C(R 10 ) 2 —, —C(R 10 ) 2 —O—C(R 10 ) 2 —, —C(R 10 ) 2 —S—C(R 10 ) 2 —, —C(R 10 ) 2 —NR PR —C(R 10 ) 2 —, —O—, —O—C(R 10 ) 2 —, —S—, —S—C(R 10 ) 2 —, —NR PR , —NH— or —NR PR —C(R 10 ) 2 —;

R 8 and R 9 independently are —C(R 10 ) 2 —, —C(R 10 ) 2 —C(R 10 ) 2 —, —O—, —O—C(R 10 ) 2 —, —S—, —S—C(R 10 ) 2 —, —NR PR — or —NR PR —C(R 10 ) 2 —, or one or both of R 8 or R 9 independently are absent, leaving a 5-membered ring;

R 13 independently is C 1-6 alkyl; and

R PR independently are —H, a protecting group or together are a protecting group, wherein 0, 1, 2, 3 or 4 of R 10A , R 10B , R 10C and R 10D are —H, R 5 and R 6 respectively are in the β,β, α,β, β,α or α,α configurations, and wherein, R 10 moieties at the 5 (if present), 8, 9 and 14 positions respectively are in the α,α,α,α, α,α,α,β, α,α,β,α, α,β,α,α, β,α,α,α, α,α,β,β, α,β,α,β, β,α,α,β, β,α,β,α, β,β,α,α, α,β,β,α, α,β,β,β, β,α,β,β, β,β,α,β, β,β,β,α or β,β,β,β configurations. For any of the F1Cs of structure 5, 6, 7, 8, 9 or 10 where two variable groups are bonded to the same carbon, e.g., R 1 , R 2 , R 3 , R 4 or R 10 at the 11 position, the each variable group at that position is independently selected.

In the F1Cs, each R 1 , R 2 , R 3 , R 4 , R 10 at the 2, 11 and 15 positions, is independently selected. In some embodiments one of the R 1 , R 2 , R 3 , R 4 , R 10 at the 2, 11 and 15 positions is hydrogen and the other is —H another moiety, but usually 2, 3, 4, 5 or 6 of the remaining variable groups are not —H, i.e., they are another moiety as defined for those groups. In other embodiments, both R 1 , R 2 , R 3 , R 4 , R 10 at the 2, 11 and 15 positions, are independently selected moieties other than hydrogen, i.e., they are another moiety as defined for those groups such as a C1-C20 organic moiety or C1-C20 optionally substituted alkyl group. In many embodiments R 1 at the 1-position in the β-configuration or R 1 at the 1-position in the α-configuration is not —H and R 4 at the 1-position in the β-configuration or R 1 at the 1-position in the α-configuration is not —H.

F1Cs include compounds having structure 2

wherein, each R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 at the 2, 5, 8, 9, 11, 14 and 15 positions, R 10A , R 10B , R 10C and R 10D are each independently chosen and have the meanings given above for compounds of structure 5, 6, 7, 8, 9 or 10;

R 3 and R 4 are, if present, both in the α-configuration or the β-configuration or one of R 3 and R 4 is in the α-configuration and the other is in the β-configuration;

D is a heterocycle, a 4-, 5-, 6- or 7-membered carbon ring, or two fused rings, each being 4-, 5-, 6- or 7-membered carbon ring, wherein 1, 2 or 3 ring carbon atoms of the 4-, 5-, 6- or 7-membered carbon ring(s) are optionally independently substituted with substituents described for substituted alkyl groups, e.g., —O—, —S— or —NR PR — or where 1, 2 or 3 hydrogen atoms of the heterocycle or where 1, 2 or 3 hydrogen atoms of the 4-, 5-, 6- or 7-membered ring are substituted with —OR PR , —SR PR , —N(R PR ) 2 , —O—Si—(R 13 ) 3 , —CHO, —CHS, —CN, —NO 2 , —OSO 3 H, —OPO 3 H, ═O, ═S, ═N—OH, ═CH 2 or a spiro ring an ester, a thioester, a thionoester, a phosphoester, a phosphothioester, a phosphonoester, a phosphiniester, a sulfite ester, a sulfate ester, a sulfoxide, a sulfamate, a sulfonate, a sulfamide, a sulfinamide, a sulfurous diamide, an amide, an amino acid, a peptide, an ether, a thioether, an acyl group, a thioacyl group, a carbonate, a carbamate, an acetal, a thioacetal, a halogen, an optionally substituted alkyl group, an optionally substituted alkenyl group, an optionally substituted alkynyl group, an optionally substituted aryl moiety, an optionally substituted heteroaryl moiety, an optionally substituted monosaccharide, an optionally substituted oligosaccharide, a nucleoside, a nucleotide, an oligonucleotide or a polymer.

In some embodiments, D comprises two 5- or 6-membered rings, wherein the rings are fused or are linked by 1 or 2 bonds, wherein 0, 1, 2 or 3 of R 7 , R 8 and R 9 are not —CHR 10 — or —C(R 10 ) 2 —.

Exemplary F1C of structure 2 include the following structures,

wherein, R 16 independently are —CH 2 —, —O—, —S— or —NH—; R 15 , R 17 and R 18 are independently selected R 1 moieties, e.g., —H, —OH, —OR PR , ═O, —SR PR , ═S, —O—Si—(R 13 ) 3 , ester, ether, acyl, halogen or an optionally substituted alkyl group; and R 19 is nitrogen or CH; R 1 -R 10 , R 10A , R 10B , R 10C and R 10D are each independently chosen and have the meanings given above for compounds of structure 5, 6, 7, 8, 9 or 10; R 10 moieties at the 5 (if present), 8, 9 and 14 positions respectively are in the α,α,α,α, α,α,α,β, α,α,β,α, α,β,α,α, β,α,α,α, α,α,β,β, α,β,α,β, β,α,α,β, β,α,β,α, β,β,α,α, α,β,β,α, α,β,β,β, β,α,β,β, β,β,α,β, β,β,β,α or β,β,β,β configurations; and R 5 and R 6 are in the β,β, β,α, α,β or α,α configurations. For F1Cs of structure 2 where two variable groups are bonded to the same carbon, e.g., R 1 , R 2 or R 10 at the 11 position, the each variable group at that position is independently selected. As shown in the structure, the R 17 moiety can be bonded to the ring carbon adjacent to R 16 , or it can be bonded to the adjacent 1, 2 or 3 ring carbons. Similarly, the R 18 moiety can be bonded to the ring carbon adjacent to R 19 , or it can be bonded to the adjacent 1, 2 or 3 ring carbons. Structure 2 F1Cs can have 1, 2, 3 or 4 of R 10A , R 10B , R 10C and R 10D as —H, but usually 2 or 3 of R 10A , R 10B , R 10C and R 10D are —H, Structure 2 compounds include structures wherein one, two or three of R 7 , R 8 and R 9 are independently —O—, —S—, or —NH— or wherein one or both of R 5 and R 6 independently are —H, —CH 3 , —CH 2 OR PR , —CH 2 OH, —CH 2 SH, —CH 2 SR PR , —CH 2 O—C(O)—C 1-10 alkyl, —CH 2 S—C(O)—C 1-10 alkyl, —CH 2 O—C(O)—C 1-10 alkenyl, —CH 2 S—C(O)—C 1-10 alkenyl, —CH 2 O—C(O)—C 0-4 alkyl-heterocycle, —CH 2 S—C(O)—C 0-4 alkyl-heterocycle, —CH 2 O—C(O)—C 0-4 alkyl-phenyl, —CH 2 S—C(O)—C 0-4 alkyl-phenyl, wherein any C alkyl, heterocycle or phenyl moiety is optionally substituted with one or more substituents, wherein the one or more substituents are one, two, three or more independently selected —O—, ═O, or R PR , —S, ═S, —SR PR , —NH—, —N(R PR ) 2 or —C(O)—NH—, wherein each R PR independently is —H or a protecting group.

The structure 2 compounds described above include

where X independently are O or S, typically both X are O. R 10α is an independently selected R 10 moiety in the α-configuration, or if a double bond is present, R 10α is absent, R 10β is an independently selected R 10 moiety in the β-configuration, R 10F is an independently selected R 10 moiety in the α- or β-configuration, n is 0, 1 or 2, and remaining variable groups are as defined above. These compounds include ones where R 1 in the α- and β-configurations independently are an R 1 moiety such as H, OH, halogen, an optionally substituted monosaccharide, an optionally substituted disaccharide or a dicarboxylic acid ester such as —OC(O)—(CH 2 ) 2 —COOH, —OC(O)—(CH 2 ) 3 —COOH or —OC(O)—(CH 2 ) 4 —COOH, R 2 in the α- and β-configurations independently are an R 2 moiety such as —H, —OH, ═O, —SH, ═S, halogen, optionally substituted alkyl, a monosaccharide or a disaccharide, R 5 is C1-C4 alkyl, R 6 is —H, halogen or C1-C4 alkyl or R 7 and R 8 independently are moieties as previously defined such as independently selected —CH 2 —, —CH(α-OR PR )—, —CH(β—OR PR )—, —C(O)— or —O—, R 9 is a moiety as previously defined such as —CH 2 —, —CH(α-halogen)-, —CH(α-OH)—, —CH(α-optionally substituted alkyl)-, —C(halogen) 2 -, —C(β-optionally substituted alkyl)(α-OH)—, —CH(α-optionally substituted alkyl)-, R 10 at the 9-position is a R 10 moiety such as —H, —F, —Cl, or optionally substituted alkyl, R PR is —H or a protecting group such as an ester or optionally substituted alkyl and other variable groups are as previously defined. For any of these compounds, 1, 2, 3 or 4 of R 10A , R 10B , R 10C and R 10D may be substituted, or they all be —H, while R 17 may be a moiety defined previously such as C1-C6 optionally substituted alkyl, e.g., —CH 3 or —C 2 H 5 .

Monosaccharides and disaccharides are described above and are optionally bonded at one or more of R 1 or other variable groups in these structure 2 or other formula 1 compounds include

where R 10A and RB independently are —H, —OH, halogen, —NH 2 , —NHR PR , —N 3 , C1-C6 alkoxy or -RD-RE, RC is —H, —OH, halogen, —NH 2 , —NHR PR , —N 3 , C1-C6 alkoxy or a monosaccharide or disaccharide linked through a glycosidic bond, RD is —NH—C(O)—, —O—C(O)—, —O—C(O)—N(R PR )—, —NH—C(O)—N(R PR )—, —O—C(S)—N(R PR )— or —C(O)—N—(R PR )—, RE is aryl, arylalkyl, alkenyl, alkyl, cycloalkyl or cycloalkyl-alkyl, where each RE is optionally independently substituted with 1, 2 or 3 independently selected halogens, —OH, ═O, —SH, ═S, —NO 2 , —CF 3 , C1-C6 alkyl, phenoxy, C1-C6 alkoxy, methylenedioxy, C1-C6 alkylsulfanyl, C1-C6 alkylsulfinyl, C1-C6 alkylsulfonyl, dimethylamino, mono- or di-C1-C6 alkylaminocarbonyl, C1-C6 alkylcarbonyl, C1-C6 alkoxycarbonyl or pyrrolidinylcarbonyl, R PR independently is —H or a protecting group such as C1-C6 optionally substituted alkyl, ester such as acetate or, if bonded to nitrogen, R PR together with the nitrogen to which it is attached is pyrrolidinyl, piperidinyl, N-methylpiperazinyl, indolinyl or morpholinyl, where the cyclic group may be monosubstituted on a carbon atom with C1-C6 alkoxycarbonyl or C1-C6 optionally substituted alkyl. In some of these embodiments, RA, RB and RC are —OH.

For any F1C of structure 2, 5, 6, 7, 8, 9 or 10, one, two or more of R 1 -R 10 , R 10A , R 10B , R 10C , R 10D , R 15 , R 17 and R 18 may be moieties that are chemically and/or enzymatically hydrolysable or removable, typically under physiological conditions, e.g., esters, thioesters, thionoesters, carbonates, amino acids, peptides and/or carbamates. Such moieties are independently chosen. These moieties will typically give rise to moieties such as to —OH, ═O, —SH or ═S at the steroid nucleus. Embodiments of F1Cs include compounds where (1) one of R 1 , R 2 and R 4 is a hydrolyzable moiety (e.g., ester, thioester, thionoester, carbonate, amino acid, peptide or carbamate), the other two of R 1 , R 2 and R 4 are —H, R 3 is not hydrogen and R 5 and R 6 are both —CH 3 , (2) two of R 1 , R 2 and R 4 are hydrolyzable moieties (e.g., independently chosen esters, thioesters, thionoesters, carbonates, amino acids, peptides and/or carbamates), the other of R 1 , R 2 and R 4 is —H, R 3 is not hydrogen and R 5 and R 6 are both —CH 3 , (3) R 1 , R 2 and R 4 are hydrolyzable moieties, R 3 is not hydrogen and R 5 and R 6 are both —CH 3 . In these embodiments, the R 3 group is typically in the β-configuration and the R 1 , R 2 and R 4 -R 6 groups are typically in the α-configuration.

In other embodiments, one or more of R 1 -R 6 , R 10 , R 15 , R 17 and R 13 , usually one, comprises an amino acid or a peptide, while the remaining groups are independently selected from the moieties defined herein. In these embodiments, the peptides are typically dimers (dipeptides) or trimers (tripeptides). For example one of R 1 , R 2 or R 4 comprises an amino acid, the remaining of R 1 , R 2 or R 4 independently comprise —OH, ═O, an ester, a carbonate or a carbamate, while R 3 is a halogen, hydroxyl or an ester and R 5 and R 6 independently are —H, —(CH 2 ) n —CH 3 , —(CH 2 ) n —CH 2 OH, or —(CH 2 ) n —CH 2 F, —(CH 2 ) 2-4 —O—(CH 2 ) 2-4 —CH 3 , where n is 0, 1, 2, 3, 4, 5, 6, 7 or 8 often 0, 1, or 2, usually 0. Typically the ester, carbonate or carbamate are hydrolyzable under physiological conditions.

Hydrolyzable or removable moieties typically comprise acyl groups, esters, ethers, thioethers, amides, amino acids, peptides, carbonates and/or carbamates. In general, the structure of hydrolyzable moieties is not critical and can vary. In some embodiments, these moieties contain a total of about 4 to about 10 carbon atoms. These hydrolyzable moieties in other embodiments comprise an organic moiety, as described above for ester, that contains 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 13, 14, 15 or 16 carbon atoms and 1, 2, 3, 4, 5, 6, 7 or 8 heteroatoms, e.g., oxygen, nitrogen or sulfur. These hydrolyzable moieties can comprise no groups that are charged in plasma, blood, intracellular cytoplasm or in the gut, or they can comprise 1, 2, 3 or more positive, negative or positive and negative charges under one or more of these conditions. The charges may be fractional depending on the group and the conditions it is under. These hydrolyzable moieties may comprise 1, 2, 3, 4 or more substitutions at a hydrogen atom(s) and/or a carbon atom(s), e.g., —OH, protected hydroxyl, —SH, protected thiol, carboxyl, protected carboxyl, amine, protected amine, —O—, —S—, —CO—, —CS—, alkoxy, alkylthio, alkenyloxy, aryl, —OP(O)(O)—O—, —OS(O)(O)—O— and/or heterocycle. Such substitutions are independently selected. Embodiments of F1Cs include ones wherein one, two, three, four or more of the variable groups that are bonded to the steroid rings, e.g., R 1 -R 6 or R 10 , comprise a moiety that can hydrolyze or metabolize to, e.g., a —H, —OH, ═O, —SH, ═S, —COOH, —NH 2 , —CH 2 OH, —CH 2 SH, —C(O)—C1-C6 alkyl-OH, —C(O)—C1-C6 alkyl-SH, —C(S)—C1-C6 alkyl-OH, —C(O)—C1-C6 alkyl or —C(O)—NH 2 atom or group.

F1Cs that comprise a hydrolyzable or removable moiety(ies) may include one or more independently chosen —O—CHR 24 C(O)OR 25 , —S—CHR 24 C(O)OR 25 , —NH—CHR 24 C(O)OR 25 , —O—CHR 24 C(S)OR 25 , —S—CHR 24 C(S)OR 25 , —NH—CHR 24 C(S)OR 25 , —O—CHR 24 OC(O)R 25 , —S—CHR 24 OC(O)R 25 , —NH—CHR 24 OC(O)R 25 , —O—CHR 24 C(O)N(R 25 ) 2 , —S—CHR 24 C(O)N(R 25 ) 2 , —NH—CHR 24 C(O)N(R 25 ) 2 , —O—CHR 24 OR 25 , —S—CHR 24 OR 25 , —NH—CHR 24 OR 25 , —O—CHR 24 C(R 25 ) 2 CH 2 OX, —S—CHR 24 C(R 25 ) 2 CH 2 OX, —NH—CHR 24 C(R 25 ) 2 CH 2 OX, —O—CHR 24 C(R 25 ) 2 OX, —S—CHR 24 C(R 25 ) 2 OX or —NH—CHR 24 C(R 25 ) 2 OX, groups that one or more of R 1 -R 6 , R 10 , R 15 , R 17 and R 13 comprise. For these hydrolyzable moieties, R 24 independently is —H, —CH 2 —C 6 H 5 , —CH 2 CH 2 —C 6 H 5 , C 1-8 alkyl, C 2-8 alkenyl, aryl or heterocycle where each alkyl, alkenyl, aryl and heterocycle moiety is independently optionally substituted with 1, 2, or 3, usually 1, —O—, —S—, —NH—, halogen, aryl, —OX, —SX, —NHX, ketone (═O) or —CN moieties or the C 1-8 alkyl is optionally substituted with 3, 4, 5 or 6 halogens, and X is —H or a protecting group. Exemplary R 24 are —H, —CH 3 , —C 2 H 5 , —C(CH 3 ) 3 , —CH 2 —C 1-5 optionally substituted alkyl, —CH 2 CH 2 —C 1-4 optionally substituted alkyl and —CH 2 CH 2 —O—C 1-4 optionally substituted alkyl. R 25 independently is —H or a C 1-30 organic moiety such as —CH 2 —C 6 H 5 , —CH 2 CH 2 —C 6 H 5 , C 1-12 alkyl, C 2-12 alkenyl, C 2-12 alkynyl, aryl, a heterocycle, —CH 2 -heterocycle or —CH 2 -aryl, where each alkyl, alkenyl, alkynyl, aryl, heterocycle, —CH 2 -heterocycle or —CH 2 -aryl moiety is independently optionally substituted with 1 or 2, usually 1, —O—, —S—, —NH—, halogen, aryl, —OX, —SX, —NHX, ketone (═O), —C(O)OX or —CN moieties or the C 1-12 alkyl, C 2-12 alkenyl or aryl, are optionally independently substituted with 3, 4, 5 or 6 halogens, where X is —H or a protecting group, or the aryl, heterocycle, —CH 2 -heterocycle or —CH 2 -aryl moieties are optionally independently substituted with 1, 2 or 3 C 1-4 alkyl moieties or with 1, 2 or 3 C 1-4 alkoxy moieties at the aryl moiety or at the heterocycle, usually at a ring carbon. Exemplary R 25 are —H, —CH 3 , —C 2 H 5 , —C 3 H 7 , —C 4 H 9 , —C 6 H 13 , —C 6 H 5 , —C 6 H 4 OH, —C 6 H 4 OCH 3 , —C 6 H 4 F, —CH 2 —C 1-5 optionally substituted alkyl, —CH 2 CH 2 —(S) 0-1 —C 1-4 optionally substituted alkyl and —CH 2 CH 2 —O—C 1-4 optionally substituted alkyl.

For any formula 1, 2, 5, 6, 7, 8, 9 or 10 compounds, whenever a variable moiety such as R 7 , R 8 or R 9 or a substitution at a variable group includes moieties such as —O—CHR 10 —, —NR PR —CHR 10 —, or ═N— it is intended that such moieties can be present in either orientation relative to the other ring atoms that may be present, i.e., —O—CHR 10 —, —NR PR —CHR 10 —, —CHR 10 —O—, —CHR 10 —NR PR —, ═N— and —N═ are all included, unless defined or implied otherwise by the structure.

Invention embodiments include a composition comprising a F1C and 1, 2, 3, 4 or more nonaqueous liquid excipients. These compositions can contain less than about 3% w/v water, less than about 2% w/v water, less than about 1.5% w/v water, less than about 1% w/v water, less than about 0.8% w/v water, less than about 0.5% w/v water, less than about 0.3% w/v water or less than about 0.1% w/v water. Typically, the nonaqueous liquid excipients include propylene glycol and a PEG or a PEG mixture and can optionally include one or both of benzyl alcohol and benzyl benzoate.

Embodiments of F1Cs include or exclude any subset of compounds within the definition of formula 1, provided that at least one F1C remains. For example, a subset of F1Cs that are may be included, for example in the invention nonaqueous formulations and in the invention intermittent dosing protocols and immune modulation methods, are (1) F1Cs where R 2 is hydroxyl, or a group that can hydrolyze or metabolize to hydroxyl or thiol, in either configuration and R 5 and R 6 are methyl in the α-configuration or (2) any 1, 2, 3, 4, 5, 6 or more of the F1Cs or genera of compounds that are disclosed herein. Another group of compounds that are optionally excluded from F1Cs comprises one or all compounds that are disclosed in one or more prior art references or publications, e.g., one or more compounds that are disclosed in one or more of the references cited herein, especially for those compounds that can render any claim or embodiment unpatentable for novelty, obviousness and/or inventive step reasons.

Other embodiments of species and genera of F1Cs include compounds of structures B, C, D, E, F and G

where the dotted lines represent double or single bonds, each R 10A , R 10B , R 10C , R 10D , R 10E (when present), R 10F , R 10G and R 10H is an independently selected single bonded R 10 moiety in the α-configuration or the β-configuration, or each R 10A , R 10B , R 10C and R 10D is an independently selected double bonded R 10 moiety (e.g., ═O or ═CH 2 ), R 1A is a single bonded R 1 moiety in the α-configuration, or R 1A together with R 1 is a double bonded moiety (e.g., ═O, ═NOH, ═CH 2 or ═CH—CH 3 ), R 2A is a single bonded R 2 moiety in the α-configuration, or R 2A together with R 2 is a double bonded moiety, R 3B is a single bonded R 3 moiety in the β-configuration, or R 3B together with R 3 is a double bonded moiety, or R 3B is absent if a double bond is present at the 16-17 position, R 4A is a single bonded R 4 moiety in the α-configuration, or R 4A together with R 4 is a double bonded moiety, or R 4A is absent if a double bond is present at the 16-17 position, and R 5 , R 6 , R 7 , R 8 and R 9 are as previously defined. When a double bond is present at the 4-5 or the 5-6 positions, R 10E is absent. For these structures, R 10A , R 10B , R 10C and R 10D may be in the α,α, α,β, β,α, or β,β configurations respectively, while R 10E , R 10F , R 10G and R 10H may be in the α,α,α,α, α,α,α,β, α,α,β,α, α,β,α,α, β,α,α,α, α,α,β,β, α,β,α,β, β,α,α,β, β,α,β,α, β,β,α,α, α,β,β,α, α,β,β,β, β,α,β,β, β,β,α,β, β,β,β,α or β,β,β,β configurations respectively, typically the α,β,α,α or β,β,α,α configurations.

Thus, when R 10E , R 10F , R 10G and R 10H respectively are in the α,β,α,α configurations and R 10A and R 10B or R 10A and R 10C or R 10A and R 10D or R 10B and R 10C or R 10B and R 10D or R 10C and R 10D are both in α-configurations exemplary B, C, D, E, F and G structures include

Similarly, when R 10E , R 10F , R 10G and R 10H respectively are in the α,β,α,α configurations and R 10A and R 10B or R 10A and R 10C or R 10A and R 10D or R 10B and R 10C or R 10B and R 10D or R 10C and R 10D respectively are in the β,α configurations exemplary B, C, D, E, F and G structures include

When R 10E , R 10F , R 10G and R 10H respectively are in the α,β,α,α configurations and R 10A and R 10B or R 10A and R 10C or R 10A and R 10D or R 10B and R 10C or R 10B and R 10D or R 10C and R 10D respectively are in the α,β configurations exemplary B, C, D, E, F and G structures include

When R 10E , R 10F , R 10G and R 10H respectively are in the α,β,α,α configurations and R 10A and R 10B or R 10A and R 10C or R 10A and R 10D or R 10B and R 10C or R 10B and R 10D or R 10C and R 10D respectively are in the β,β configurations exemplary B, C, D, E, F and G structures include

When R 10E , R 10F , R 10G and R 10H respectively are in the β,β,α,α configurations exemplary B, C, D, E, F and G structures include

When a double bond is present at the 5-6 position, and R 10F , R 10G and R 10H respectively are in the β,α,α configurations exemplary B, C, D, E, F and G structures include

When a double bond is present at the 1-2 and 5-6 positions, and R 10F , R 10G and R 10H respectively are in the β,α,α configurations exemplary B, C, D, E, F and G structures include

When a double bond is present at the 5-6 and 16-17 positions, and R 10F , R 10G and R 10H respectively are in the β,α,α configurations exemplary B, C, D, E, F and G structures include

When R 6 and R 10C are linked through a —CH 2 —O— moiety there is no double bond at the 5-6 position and exemplary F1C structures include

When adjacent variable groups are an epoxide or an optionally substituted cyclopropyl ring exemplary F1C structures include

wherein variable groups are independently selected and, when not specified otherwise, are in the α- or β-configuration.

Substituents at the cyclopropyl ring include one or two halogen atoms, e.g., dichloro, dibromo or difluoro. Typically these F1C contain one or two epoxide or cyclopropyl moieties.

Other F1Cs and structures having B, C, D, E, F and G structures are apparent from the foregoing descriptions and variable group definitions.

Thus, exemplary F1C, e.g., 2, 5, 6, 7, 8, 9, 10, B, C, D, E, F and G structures are characterized as having the following:

(1) a double bond at the 5-6 position, no double bonds with R 10E at the 5 position in the α-configuration, no double bonds with R 10E in the β-configuration, a double bond at the 4-5 position, a double bond at the 1-2 position with R 10E in the α-configuration, a double bond at the 1-2 position with R 10E in the β-configuration, double bonds at the 1-2 and 4-5 positions, double bonds at the 1-2 and 5-6 positions, a double bond at the 16-17 position with R 10E in the α-configuration, a double bond at the 16-17 position with R 10E in the β-configuration, double bonds at the 4-5 and 16-17 positions, double bonds at the 5-6 and 16-17 positions, double bonds at the 1-2 and 16-17 positions with R 10E in the α-configuration, double bonds at the 1-2 and 16-17 positions with R 10E in the β-configuration, double bonds at the 1-2, 5-6 and 16-17 positions or double bonds at the 1-2, 4-5 and 16-17 positions, and

(2) R 10A , R 10B , R 10C and R 10D are independently selected R 10 groups in the α,α, α,β, β,α or β,β configurations respectively, and

(3) R 10E , R 10F , R 10G and R 10H are independently selected R 10 groups in the α,α,α,α, α,α,α,β, α,α,β,α, α,β,α,α, β,α,α,α, α,α,β,β, α,β,α,β, β,α,α,β, β,α,β,α, β,β,α,α, α,β,β,α, α,β,β,β, β,α,β,β, β,β,α,β, β,β,β,α or β,β,β,β configurations respectively, and

(4) R 1A , R 2A , R 3B and R 4A are —H, R 1A is not —H and R 2A , R 3B and R 4A are —H, R 2A is not —H and R 1A , R 3B and R 4A are —H, R 3B is not —H and R 1A , R 2A and R 4A are —H, R 4A is not —H and R 1A , R 2A and R 3B are —H, R 1A and R 2A are not —H and R 3B and R 4A are —H, R 1A and R 3B are not —H and R 2A and R 4A are —H, R 1A and R 4A are not —H and R 2A and R 3B are —H, R 2A and R 3B are not —H and R 1A and R 4A are —H, R 2A and R 4A are not —H and R 1A and R 3B are —H, R 3B and R 4A are not —H and R 1A and R 2A are —H, R 1A , R 2A and R 3B are not —H and R 4A is —H, R 1A , R 2A and R 4A are not —H and R 3B is —H, R 1A , R 3B and R 4A are not —H and R 2A is —H, R 2A , R 3B and R 4A are not —H and R 1A is —H, R 1A , R 2A , R 3B and R 4A are not —H, R 1A and R 2A are —H and R 3B and R 4A are absent (i.e., a 16-17 double bond is present), R 1A is —H and R 2A is not —H and R 3B and R 4A are absent, R 2A is —H and R 1A is not —H and R 3B and R 4A are absent, or, R 1A and R 2A are not —H and R 3B and R 4A are absent, where each R 1A , R 2A , R 3B and R 4A are independently selected, and

(5) each R 1 , R 2 , R 3 and R 4 are independently selected.

For these exemplary formula B, C, D, E, F and G structures and any other F1C structures disclosed herein, each R 1 , R 1A , R 2 , R 2A , R 3 , R 3B , R 4 , R 4A , R 10 , R 10A , R 10B , R 10C , R 10D , R 10E , R 10F and R 10G are an independently selected atom or moiety as described herein, e.g., —H, —OH, ═O, —SH, ═S, —F, —Cl, —Br, —I, —CN, —SCN, —N 3 , —NH—C1-C8 optionally substituted alkyl, —N(C1-C8 optionally substituted alkyl) 2 where each optionally substituted alkyl moiety is the same or different, protected ketone, e.g., ethylene ketal (—O—CH 2 —CH 2 —O—), —NO 2 , —ONO 2 , —(CH 2 ) n —CH(O), —(CH 2 ) n —COOH, —(CH 2 ) n —COOR PR , —(CH 2 ) n —NHCH 3 , —(CH 2 ) n —NHR PR , —(CH 2 ) n —CH(S), —O—S(O)(O)—OH, —O—P(O)(O)—OH, where n is 0, 1, 2, 3, 4, 5 or 6, —O-β-D-glucopyranosiduronate, —OP(O)(OH)—NH—C(═NH)—N(CH 3 )—CH 2 —C(O)OH, or a group such as:

optionally substituted alkyl, e.g., —CH 3 , —C 2 H 5 , —CH 2 CH 2 CH 3 , —CH 2 CH 2 CH 2 CH 3 , —CH 2 CH 2 OCH 2 CH 3 , —CH 2 OH, —CH 2 CH 2 OH, —CHOHCH 3 , —CH(OC(O)CH 3 )—CH 3 , —CH(OR PR )—CH 3 , —CHOH—(CH 2 ) n —OH, —CH(OR PR )—(CH 2 ) n —OR PR , —CHOH—(CH 2 ) n —CH 2 OH, —CH(OR PR )—(CH 2 ) n —CH 2 OR PR , —CHOH—(CH 2 ) n —CH 2 SH, —CH(OR PR )—(CH 2 ) n —CH 2 SR PR , —CH 2 —(CH 2 ) n —OCH 3 , —CF 3 , —(CH 2 ) t —CF 3 , —(CH 2 ) t —NH 2 , —(CH 2 ) 2 —NH 2 , —(CH 2 ) 3 —NH 2 , —CH 2 —NHCH 3 , —(CH 2 ) 2 —NHCH 3 , —(CH 2 ) 3 —NHCH 3 , —(CH 2 ) t —N(CH 3 ) 2 , —(CH 2 ) n —CH 2 OH, —(CH 2 ) n —CH 2 F, —(CH 2 ) n —CH 2 Cl, —(CH 2 ) n —CH 2 Br, —CH(CH 3 )—(CH 2 ) 3 —CH(CH 3 ) 2 , —CH(CH 3 )—(CH 2 ) n —CH(CH 3 ) 2 , —CH(CH 3 )—(CH 2 ) 3 —CH(CH 3 )—CH 2 OH, —CH(CH 3 )—(CH 2 ) n —CH(CH 3 )—CH 2 OH, —CH(CH 3 )—(CH 2 ) 3 —CH(CH 3 )—CH 2 F, —CH(CH 3 )—(CH 2 ) n —CH(CH 3 )—CH 2 F, —CH(CH 3 )—(CH 2 ) 3 —CH(CH 3 )—CH 2 Cl, —CH(CH 3 )—(CH 2 ) n —CH(CH 3 )—CH 2 Cl, —CH(CH 3 )—(CH 2 ) 3 —CH(CH 3 )—CH 2 Br, —CH(CH 3 )—(CH 2 ) n —CH(CH 3 )—CH 2 Br, —CH(CH 3 )—(CH 2 ) 3 —CH(CH 2 F) 2 , —CH(CH 3 )—(CH 2 ) n —CH(CH 2 F) 2 , —(CH 2 ) 3 —CH(CH 3 ) 2 , —(CH 2 ) n —CH(CH 3 ) 2 , —(CH 2 ) 3 —CH(CH 3 )—CH 2 OH, —(CH 2 ) n —CH(CH 3 )—CH 2 OH, —(CH 2 ) 3 —CH(CH 3 )—CH 2 F, —(CH 2 ) n —CH(CH 3 )—CH 2 F, —(CH 2 ) 3 —CH(CH 3 )—CH 2 Cl, —(CH 2 ) n —CH(CH 3 )—CH 2 Cl, —(CH 2 ) 3 —CH(CH 3 )—CH 2 Br, —(CH 2 ) n —CH(CH 3 )—CH 2 Br, —(CH 2 ) 3 —CH(CH 2 F) 2 , —CH 3 , —CH 2 CH 3 , —CH 2 CH 2 CH 3 , —CH 2 OH, —CH 2 CH 2 OH, —CH 2 CH 2 CH 2 OH, —CH 2 CH(OH)CH 3 , —(CH 2 ) n —CH(CH 2 F) 2 , —CH(CH 3 )—(CH 2 ) n —CH(CH 2 CH 3 )—CH(CH 3 ) m (CH 2 R 51 )P, —C≡CH, —C≡CCH 3 , —C≡CCF 3 , —C≡CCl, —CH═CH 2 , —CF═CF 2 , —CF═CFCH 3 , —CH═CHCH 3 , —C(O)—NH—C 6 H 5 , —C(O)—NH—CH 3 , —C(O)—NH—C 2 H 5 , —C(CH 3 )═N—OH, —C(CH 3 )═N—NH—C(O)—OC 2 H 5 , —C(CH 3 )═N—NH—C(O)—OC 4 H 9 , —C(CH 3 )═N—NH—C(O)—OC 6 H 5 , —CH 2 —C 6 H 5 , —CH 2 —C 6 H 5 (CH 2 ) n —F, —C 6 H 5 , —C 6 H 4 (CH 2 ) n —F, —C 6 H 4 (CH 2 ) n —OH, —C 6 H 4 (CH 2 ) n —C(O)OH, —C 6 H 4 (CH 2 ) n —C(O)OCH 3 , —CH═CH—(CH 2 ) n —CH 3 , —CH(CH 3 )—(CH 2 ) n —CH 2 —C(H) q (CH 3 ) m (CH 2 R 51 ) p , —CH(CH 3 )—(CH 2 ) n —CH═C(CH 3 )(CH 2 OH), —CH(CH 2 OH)—(CH 2 ) n —CH═C(CH 3 ) 2 , ═CH—(CH 2 ) n -R 45 , ═CH—(CH 2 ) t —(CH═CH)—R 45 , ═C(CH 3 )—CH 2 —C(O)—N(C1-C6 alkyl) 2 , ═C(CH 3 )—(CH 2 ) 2 —C(O)—N(C1-C6 alkyl) 2 , ═C(CH 3 )—CH 2 —C(O)—NH—C1-C6 alkyl, ═C(CH 3 )—(CH 2 ) 2 —C(O)—NH—C1-C6 alkyl, ═C(CH 3 )—CH 2 —N(C1-C6 alkyl) 2 , ═C(CH 3 )—(CH 2 ) 2 —N(C1-C6 alkyl) 2 , ═C(CH 3 )—CH 2 —NH—C1-C6 alkyl, ═C(CH 3 )—(CH 2 ) 2 —NH—C1-C6 alkyl, ═CH—CH 2 —C(O)—N(C1-C6 alkyl) 2 , ═CH—(CH 2 ) 2 —C(O)—N(C1-C6 alkyl) 2 , ═CH—CH 2 —C(O)—NH—C1-C6 alkyl, ═CH—(CH 2 ) 2 —C(O)—NH—C1-C6 alkyl, ═CH—CH 2 —N(C1-C6 alkyl) 2 , ═CH—(CH 2 ) 2 —N(C1-C6 alkyl) 2 , ═CH—CH 2 —NH—C1-C6 alkyl, ═CH—(CH 2 ) 2 —NH—C1-C6 alkyl, ═C(CH 3 )—CH 2 —C(O)—NH 2 , ═C(CH 3 )—(CH 2 ) 2 —C(O)—NH 2 , ═C(CH 3 )—(CH 2 ) 2 —NH 2 , ═C(CH 3 )—CH 2 —NH 2 , ═CH—CH 2 —C(O)—NH 2 , ═CH—(CH 2 ) 2 —C(O)—NH 2 , ═CH—CH 2 —NH 2 or ═CH—(CH 2 ) 2 —NH 2 , where R 45 is an R 1 substituent disclosed herein, e.g., —H, —OH, —F, —Cl, —Br, —I, —OCH 3 , —C(O)OH, —C(O)OCH 3 , —OR PR , —SH, —SR PR , —NH 2 —NH—C1-C8 optionally substituted alkyl, —N(C1-C8 optionally substituted alkyl) 2 where each optionally substituted alkyl moiety is the same or different, or —NHR PR , R 51 independently are an R 1 substituent disclosed herein, e.g., an ester, —F, —Cl, —Br, —I, alkyl (e.g., —CH 3 ), an ether (e.g., (—OCH 3 ), a thioether (e.g., (—SCH 3 ), an optionally substituted heterocycle, —C(O)OH, —NH 2 or —CN, m is 0, 1, 2 or 3, n is 0, 1, 2, 3, 4, 5 or 6, p is 0, 1, 2 or 3, q is 0, 1, 2 or 3, t is 1, 2, 3, 4, 5 or 6 and R PR are —H or independently selected protecting groups, or

optionally substituted alkenyl, e.g., ═CH 2 , ═CH 2 CH 3 , ═CH—CH 2 OH, ═CH—(CH 2 ) n —OR PR , —CH═CH 2 , —CH═CHF, —CH═CHCl, —CH═CHBr, —CH═CHI, —CH═CH—(CH 2 ) n —OH, —CH═CH—(CH 2 ) n —F, —CH═CH—(CH 2 ) n —Cl, —CH═CH—(CH 2 ) n —Br, —CH═CH—(CH 2 ) n -1, —CH═NCH 3 , —CH═NR PR , —CH═N—CH 3 , —CH═CH—CH 3 , —CH═CH—(CH 2 ) n —COOR PR , —CH═CH—(CH 2 ) n —NHR PR , —CH═CH—CH 2 —OR PR , —CH═CH—CH 2 —CF 3 , —CH═CH 2 —CH 2 -halogen, —CH═CH—(CH 2 ) n —OCH 3 , —CH═CH—(CH 2 ) n —C(O)—O-optionally substituted alkyl, —CH═CH—(CH 2 ) n —C(O)—S-optionally substituted alkyl, ═CH—CH 2 —(CH 2 ) n —SR PR , ═CH—(CH 2 ) n —C(O)NHR PR , ═CH—(CH 2 ) n —C(O)NHCH 3 , ═CH—(CH 2 ) n —C(O)NHC 2 H 5 , ═CH—CH 2 CH 3 , ═CH—(CH 2 ) n —CH(CH 3 ) 2 , ═CH—(CH 2 ) n —CH(CH 3 )(CH 2 OR PR ), ═CH—(CH 2 ) n —CH(CH 3 )(CH 2 C(O)OR PR ), ═CH—(CH 2 ) n —OH, ═CCH 3 —(CH 2 ) n —OR PR , ═CCH 3 —(CH 2 ) n —C(O)OR PR , ═CCH 3 —(CH 2 ) n —C(O)NHR PR , ═CCH 3 —(CH 2 ) n -halogen, ═CH—CHOH—CH 2 —OH or ═CH—CH 2 CH 2 -halogen, where R PR is —H or a protecting group and n is 0, 1, 2, 3, 4, 5 or 6, or

optionally substituted alkynyl, e.g., —C≡CH, —C≡C—(CH 2 ) m —OH, —C≡C—halogen, —C≡C—CH 3 , —C≡CCF 3 , —C≡CCH 2 F, —C≡CCH 2 Cl, —C≡CCH 2 Br, —C≡CCH 2 I, —C≡C—CH 2 OH, —C≡C—CH 2 -halogen, —C≡C—CH 2 —C(O)OR PR , —C≡C—CH 2 —CH 3 , —C≡CCH 2 CF 3 , —C≡C—CH 2 —CH 2 OH, —C≡C—CH 2 —CH 2 -halogen, —C≡C—(CH 2 ) n —C 6 H 5 , —C≡C—(CH 2 ) n —C 6 H 4 OH, —C≡C—(CH 2 ) n —C 6 H 4 COOR PR , —C≡C—(CH 2 ) n —C 6 H 3 (OH) 2 , —C≡C—(CH 2 ) n —C 6 H 4 F, —C≡C—(CH 2 ) n —C 6 H 4 Br, —C≡C—CH 2 —CH 2 —C(O)OR PR , —C≡C—(CH 2 ) n —CH 3 , —C≡C—CH(CH 3 )—(CH 2 ) n —CH 3 , —C≡C—(CH 2 ) n —CHOR PR , —C≡C—CH(CH 3 )—(CH 2 ) n —CHOR PR , —C≡C—(CH 2 ) n —CHCOOR PR , —C≡C—CH(CH 3 )—(CH 2 ) n —NHR PR , —C≡C—(CH 2 ) n —NHR PR , —C≡C—(CH 2 ) n —C(O)NH—(CH 2 ) n —CH 3 , —C≡C—C≡C—(CH 2 ) n —CH 3 , —C≡C—C≡C—(CH 2 ) n -halogen, —C≡C—(CH 2 ) n —OS(O)(O)—O—R PR , —C≡C—(CH 2 ) n —OS(O)(O)—O-optionally substituted alkyl, —C≡C—C≡C—(CH 2 ) n —OR PR or —C≡C—CH(CH 3 )—(CH 2 ) n —CHOR PR , where n is 0, 1, 2, 3, 4, 5 or 6, m is 1, 2, 3 or 4 and R PR is —H or a protecting group, or

optionally substituted aryl, optionally substituted alkylaryl, optionally substituted alkenylaryl or optionally substituted alkynylaryl, e.g., optionally substituted phenyl, optionally substituted benzyl, —(CH 2 ) n —C 6 H 4 OH, —(CH 2 ) n —C 6 H 4 OR PR , —(CH 2 ) n —C 6 H 3 (OH) 2 , —(CH 2 ) n —C 6 H 4 F, —(CH 2 ) n —C 6 H 4 Br, —(CH 2 ) n —C 6 H 4 C(O)OR PR , —(CH 2 ) n —C 6 H 4 C(O)SR PR , or analogs where the aromatic ring contains 1, 2, 3 or 4 independently chosen substituents such as independently chosen halogen, —OH, —SH, —NO 2 , —CN, —SCN, —N 3 , C1-C6 ester, C1-C6 alkyl, C1-C6 ether, C1-C6 thioether, —OR PR , —(CH 2 ) n —C(O)OR PR , —(CH 2 ) n —NHR PR , —(CH 2 ) n —OR PR or —(CH 2 ) m —O—(CH 2 ) m —OR PR where n is 0, 1, 2, 3, 4, 5 or 6, m independently are 1, 2 or 3 and R PR independently are —H or a protecting group, or

ether, e.g., optionally substituted alkoxy, optionally substituted alkenyloxy, optionally substituted alkynyloxy, optionally substituted aryloxy, —OCH 3 , —OC 2 H 5 , —OC 3 H 7 , —OC 4 H 9 , —OC 2 H 3 , —OC 3 H 5 , —OC 4 H 7 , —O—C(CH 3 ) 3 , —OCH 2 CH 2 OH, —O(CH 2 ) 2 —O—CH 3 , —O(CH 2 ) 3 —O—CH 3 , —O—CH(CH 3 )CH 3 , —O—CH 2 CH 2 CH 3 , —OCH 2 CH 2 F, —OCH 2 CHF 2 , —OCH 2 CF 3 , —OCH 2 CH 2 Cl, —OCH 2 CH 2 Br, —OCH 2 CH 2 I, —OCH 2 CH 2 CH 2 F, —O—CH 2 —CH(C(O)—NH—CH 2 C(O)OH)—NH—C(O)—(CH 2 ) 2 —CH(NH 2 )—C(O)—OH, —O—(CH 2 ) 2 —N + (CH 3 ) 3 ,), —O—(CH 2 ) 0-3 —(CH═CH) 0-1 —(CH 2 ) 0-3 —CH 3 , —O—(CH 2 ) 0-3 —(CH═CH)—(CH 2 ) 0-3 —CH 2 F, —O—(CH 2 ) 1-3 —(C≡C)—(CH 2 ) 0-3 —CH 3 , —O—(CH 2 ) 1-3 —(C≡C)—(CH 2 ) 0-3 —CH 2 F, —O—C 6 H 5 , —O—CH 2 —C 6 H 5 , —O—C1-C20 organic moiety where the organic moiety is, e.g., —CH 3 , —C 2 H 5 , i-propyl, n-propyl, t-butyl, n-butyl, l-butyl, n-hexyl, n-octyl, n-decyl, —(CH 2 ) 1-8 —OH, —CHO, —(CH 2 ) 1-8 —NH 2 , —(CH 2 ) 1-8 —C(O)—OH, —(CH 2 ) 0-3 —(CH═CH) 0-1 —(CH 2 ) 0-3 —CH 3 , —(CH 2 ) 0-3 —(CH═CH) 0-1 —(CH 2 ) 0-3 —CH 2 F, —(CH 2 ) 0-3 —(CH═CH) 0-1 —(CH 2 ) 0-3 —CH 2 Br, —(CH 2 ) 0-3 —(CH═CH) 0-1 —(CH 2 ) 0-3 —C(O)—OR PR , —(CH 2 ) 0-3 —(CH═CH) 0-1 —(CH 2 ) 0-3 —NHR PR , —C(O)—CH 3 , —C(O)—C 2 H 5 , —C(O)—C 6 H 5 , —CF 3 , —CH 2 CF 3 or —C 2 F 5 , wherein R PR is —H or a protecting group, —O—C 1-10 optionally substituted alkyl such as i-propyl, n-propyl, t-butyl, n-butyl, n-hexyl, n-octyl, n-decyl, —(CH 2 ) 1-8 —OH, —(CH 2 ) 1-8 —NH 2 , —(CH 2 ) 1-8 —C(O)—OH, —(CH 2 ) 0-3 —(CH═CH) 0-1 —(CH 2 ) 0-3 —CH 3 , —(CH 2 ) 0-3 —(CH═CH) 0-1 —(CH 2 ) 0-3 —CH 2 F, —(CH 2 ) 0-3 —(CH═CH) 0-1 —(CH 2 ) 0-3 —CH 2 Br, —(CH 2 ) 0-3 —(CH═CH) 0-1 —(CH 2 ) 0-3 —C(O)—OR PR , —(CH 2 ) 0-3 —(CH═CH) 0-1 —(CH 2 ) 0-3 —NHR PR , —CF 3 and —C 2 F 5 , wherein R PR is —H or a protecting group, or

ester, e.g., —OC(O)CH 3 , —OC(O)C 2 H 5 , —OC(O)C 2 H 3 , —OC(O)CH 2 CH 2 CH 3 , —OC(O)CH(CH 3 ) 2 , —O—C(O)—(CH 2 ) 2 —C(O)OH, —O—C(O)—(CH 2 ) 2 —C(O)OR PR , —O—C(O)—(CH 2 ) 3 —C(O)OH, o—C(O)—(CH 2 ) 3 —C(O)OR PR , —O—C(O)—(CH 2 ) 4 —C(O)OH, —O—C(O)—(CH 2 ) 5 —C(O)OH, —O—C(O)—(CH 2 ) 5 —C(O)OR PR , —O—C(O)—(CH 2 ) 4 —C(O)OR PR , —O—C(O)—(CH 2 ) 2 —C(O)ONH 2 , —C(O)—(CH 2 ) 2 —C(O)ONHCH 3 , —O—C(O)—(CH 2 ) 2 —C(O)ONHC 2 H 5 , —O—C(O)—(CH 2 ) 2 —C(O)ONHC 3 H 7 , —O—C(O)—(CH 2 ) 2 —C(O)ONHC 3 H 5 , —O—C(O)—(CH 2 ) 2 —C(O)ONHR PR , —O—C(O)—(CH 2 ) 2 —C(O)ON(R PR ) 2 , —OC(O)—C(CH 3 ) 2 —(CH 2 ) m —CH 3 , —OC(O)—(CH 2 ) m —CH 3 , —OC(O)—CH(CH 3 )—(CH 2 ) m —CH 3 , —OC(O)—C(CF 3 ) 2 —(CH 2 ) m —CH 3 , —OC(O)—CH(CF 3 )—(CH 2 ) m —CH 3 , —OC(O)C 3 H 7 , —OC(O)C 3 H 5 , —OC(O)C 4 H 9 , —OC(O)C 4 H 7 , —OC(O)C(CH 3 ) 3 , —OC(O)CH 2 CH 2 CH 2 CH 3 , —OC(O)C 6 H 5 , —OC(O)CH 2 C 6 H 5 , —OC(O)—(CH 2 ) 2 —C(O)OH, —OC(O)—(CH 2 ) 2 —C(O)OCH 3 , —OC(O)—(CH 2 ) 3 —C(O)OH, —OC(O)—(CH 2 ) 3 —C(O)OCH 3 , —OC(O)—(CH 2 ) 4 —C(O)OH, —OC(O)—(CH 2 ) 4 —C(O)OCH 3 , —OC(O)—CH(CH 3 )—CH 2 —C(O)OH, —OC(O)—CH(CH 3 )—CH 2 —C(O)OCH 3 , —OC(O)—CH(CH 3 )—(CH 2 ) 2 —C(O)OH, —OC(O)—CH(CH 3 )—(CH 2 ) 2 —C(O)OCH 3 , —OC(O)—C(CH 3 ) 2 —CH 2 —C(O)OH, —OC(O)—C(CH 3 ) 2 —CH 2 —C(O)OCH 3 , —OC(O)—C(CH 3 ) 2 —(CH 2 ) 2 —C(O)OH, —OC(O)—C(CH 3 ) 2 —(CH 2 ) 2 —C(O)OCH 3 , —OC(O)—(CH 2 ) 2 —C(O)OH, —O—C(O)—C(O)—O—(CH 2 ) m —CH 3 , —C(O)—C(O)—O—(CH 2 ), —CH 2 OH, —O—C(O)—(CH 2 ) n —C(O)—O—(CH 2 ) m —CH 3 , —O—C(O)—(CH 2 ) n —C(O)—O—(CH 2 )—CH 2 OH, —C(O)—CH(NH 2 )—CH 2 OH, —O—C(O)—CH 2 —N(CH 3 )—C(═NH)—NH 2 , —O—C(O)—CH 2 —NH—C(O)—CH(CH 2 SH)—NH—C(O)—(CH 2 ) 2 —CH(NH 2 )—C(O)—OH, a C2-C20 ester such as —O—C(O)—CH 3 , —O—C(O)—CF 3 , —O—C(O)—CCl 3 , —O—C(O)—C 2 H 5 , —O—C(O)—C 4 H 7 , —O—C(O)—C 6 H 5 , —O—C(O)—(CH 2 ) 2 —CH 3 , —O—C(O)—(CH 2 ) 3 —CH 3 , —O—C(O)—(CH 2 ) 4 —CH 3 , —O—C(O)—(CH 2 ) 5 —CH 3 , —O—C(O)—(CH 2 ) 6 —CH 3 , —O—C(O) 2 furanyl, —O—C(O) 2 thiophenyl, —O—C(O) 2 pyrrolyl, —O—C(O) 2 pyrimidinyl, —O—C(O) 3 pyrimidinyl, —O—C(O) 2 pyridyl, —O—C(O) 3 pyridyl, —O—C(O)-heterocycle, —O—C(O)—(CH 2 ) m —C(O)O—C1-C10 optionally substituted alkyl, —O—C(O)—(CH 2 ) m —C(O)O—C2-C10 optionally substituted alkenyl, —O—C(O)—(CH 2 ) m —O—(CH 2 ) m —C(O)O—C1-C10 optionally substituted alkyl, —C(O)—(CH 2 ) m —(CH 2 ) m —C(O)OR PR , —O—C(O)—(CH 2 ) m —S—(CH 2 ) m —C(O)O—C1-C10 optionally substituted alkyl, —O—C(O)—(CH 2 ) m —S—(CH 2 ) m —C(O)OR PR , —O—C(O)—(CH 2 ) m —NR PR —(CH 2 ) m —C(O)O—C1-C10 optionally substituted alkyl, —O—C(O)—(CH 2 ) m —NR PR —(CH 2 ) m —C(O)OR PR , —O—C(O)—C 1-12 optionally substituted alkyl, —OC(O)—(CH 2 ) q —C(O)OH, —OC(O)—(CH 2 ) q —C(O)O—C 1-8 optionally substituted alkyl, —OC(O)—CH(CH 3 )—(CH 2 ) q —C(O)OH, —OC(O)—CH(CH 3 )—(CH 2 ) q —C(O)O—C 1-8 optionally substituted alkyl, —OC(O)—C(CH 3 ) 2 —(CH 2 ) q —C(O)OH, —OC(O)—C(CH 3 ) 2 —(CH 2 ) q —C(O)O—Cl 8 optionally substituted alkyl, —OC(O)—C(C 2 H 5 )(CH 3 )—(CH 2 ) q —C(O)OH, —OC(O)—C(C 2 H 5 )(CH 3 )—(CH 2 ) q —C(O)O—Cl 8 optionally substituted alkyl, —OC(O)—C(C 2 H 5 ) 2 —(CH 2 ) q —C(O)OH, —OC(O)—C(C 2 H 5 ) 2 —(CH 2 ) q —C(O)O—C 1-8 optionally substituted alkyl, —OC(O)—C(C 2 H 5 )(C 3 H 7 )—(CH 2 ) q —C(O)OH, —OC(O)—C(C 2 H 5 )(C 3 H 7 )—(CH 2 ) q —C(O)O—C 1-8 optionally substituted alkyl, where the optionally substituted alkyl optionally is methyl, ethyl, i-propyl, n-propyl, t-butyl, n-butyl, n-hexyl, n-octyl, n-decyl, vinyl, allyl, phenyl, monosubstituted phenyl, disubstituted phenyl, trisubstituted phenyl, —CH 2 OH, —CH 2 OR PR , —CH 2 F, —CF 2 H, —(CH 2 ) n —CH 3 , —(CH 2 ) n —OH, —(CH 2 ) n —F, —(CH 2 ) n —Br, —(CH 2 ) n —NH 2 , —(CH 2 ) n —C(O)—OR PR , —(CH 2 ) n —O—CH 3 , —(CH 2 ) n —S—CH 3 , —(CH 2 ) m —(CH═CH) p —(CH 2 ) q —CH 3 , —(CH 2 ) m —(CH═CH) p —(CH 2 ) q —CH 2 F, —(CH 2 ) m —(CH═CH) p —(CH 2 ) q —CH 2 Br, —(CH 2 ) m —(CH═CH) p —(CH 2 ) q —C(O)—OR PR , —(CH 2 ) m —(CH═CH) p —(CH 2 ) q —NHR PR , —CF 3 , —CH 2 CF 3 or —C 2 F 5 , wherein R PR independently are —H, a protecting group such as C1-C10 optionally substituted alkyl (e.g., —CH 3 , —C 2 H 5 , —C 3 H 6 OH) or together are a protecting group, n is 1, 2, 3, 4, 5, 6, 7 or 8, m is 0, 1, 2, 3, 4, 5 or 6, p is 0 or 1 and q is 0, 1, 2, 3, 4, 5 or 6, or

acyl, e.g., —C(O)OH, —C(O)—CH 2 OH, —C(O)—CH 2 F, —C(O)—CH 2 Cl, —C(O)—CH 2 Br, —C(O)—CH 2 I, —C(O)—CH 2 COOH, —C(O)—CH 2 COOR PR , —C(O)—CH 3 , —C(O)—CF 3 , —C(O)—CH 2 CF 3 , —C(O)—CH(NH 2 )—CH 2 OH, —C(O)—CH 2 —N(CH 3 )—C(═NH)—NH 2 , —C(O)—(CH 2 ) n —CH 2 OH, —C(O)—O—C(O)—C(CH 3 ) 3 , —C(O)—O—C(O)—CH(CH 3 ) 2 , —C(O)—O—C(O)—CH 3 , —C(O)—O—C(O)—C 2 H 5 , —C(O)—(CH 2 ) n —CH 2 F, —C(O)—N(CH 3 ) 2 , —C(O)—N(C 2 H 5 ) 2 , —C(O)—N(CH 3 )(C 2 H 5 ), —C(O)—NH[C(CH 3 ) 3 ], —C(O)—NH(CH 3 ), —C(O)NH 2 , —C(O)—N(R PR ) 2 , —C(O)—(CH 2 ) n —CH 2 Cl, —C(O)—(CH 2 ) n —CH 2 Br, —C(O)—(CH 2 ) n —CH 2 —C(O)OH, —C(O)—(CH 2 ) n —CH 2 —NH 2 , —C(O)—CH(CH 3 )—(CH 2 ) 3 —CH(CH 3 ) 2 , —C(O)—CH(CH 3 )—(CH 2 ) n —CH(CH 3 ) 2 , —C(O)—CH(CH 3 )—(CH 2 ) 3 —CH(CH 3 )—CH 2 OH, —C(O)—CH(CH 3 )—(CH 2 ) n —CH(CH 3 )—CH 2 OH, —C(O)—CH(CH 3 )—(CH 2 ) 3 —CH(CH 3 )—CH 2 F, —C(O)—CH(CH 3 )—(CH 2 ) n —CH(CH 3 )—CH 2 F, —C(O)—CH(CH 3 )—(CH 2 ) 3 —CH(CH 3 )—CH 2 Cl, —C(O)—CH(CH 3 )—(CH 2 ) n —CH(CH 3 )—CH 2 Cl, —C(O)CH 3 , —C(O)CHO, —C(O)CH 2 OH, —C(O)CH 2 F, —C(O)CH 2 Cl, —C(O)CH 2 Br, —C(O)—CH 2 OH, —C(O)—CH 2 OR PR , —C(O)—(CH 2 ) n —CH 2 OH, —C(O)—(CH 2 ) n —CH 2 OR PR , —C(O)—S—(CH 2 ) n —CH 2 F, —C(O)—S—(CH 2 ) n —CHF 2 , —C(O)—S—(CH 2 ) n —CF 3 , —C(O) 2 furanyl, —C(O)-2 thiophenyl, —C(O)-2 pyrrolyl, —C(O)-2 pyrimidinyl, —C(O)-3 pyrimidinyl, —C(O)-2 pyridyl, —C(O)-3 pyridyl, —C(O)-heterocycle, —C(O)—C1-C10-optionally substituted alkyl, —C(O)—NH-optionally substituted phenyl, —C(O)—NH-optionally substituted heterocycle, —C(O)—(CH 2 ) n -optionally substituted heterocycle, —C(O)—(CH 2 ) n -optionally substituted phenyl, or —C(O)NR 50 R 51 where R PR independently are —H or a protecting group such as C1-C10 optionally substituted alkyl, m is 0 or 1, n is 0, 1, 2, 3, 4, 5 or 6, and R 50 and R 51 independently are —H, optionally substituted phenyl, optionally substituted phenylalkyl, optionally substituted alkyl optionally substituted alkenyl, or an optionally substituted heterocycle, e.g., pyridyl, pyrrolyl, pyrimidyl, benzimidazolyl, benzoxazolyl, benzofuranyl, —CH 3 , —C 2 H 5 , 2-, 3- or 4-fluorophenyl, 2-, 3- or 4-chlorophenyl, 2-, 3- or 4-methoxyphenyl 2-, 3- or 4-methylphenyl or 2-, 3- or 4-trifluoromethylphenyl, or

thioester, e.g., —SC(O)CH 3 , —SC(O)C 2 H 5 , —SC(O)C 3 H 7 , —SC(O)C 4 H 9 , —SC(O)C 6 H 5 , —SC(O)CH 2 C 6 H 5 , —C(O)SCH 3 , —CS(O)C 2 H 5 , —CS(O)C 3 H 7 , —CS(O)C 4 H 9 , —CS(O)C 6 H 5 , —CS(O)CH 2 C 6 H 5 , —S—C(O)—(CH 2 ) 2 —C(O)OH, —S—C(O)—(CH 2 ) 2 —C(O)OR PR , —S—C(O)—(CH 2 ) 3 —C(O)OH, S—C(O)—(CH 2 ) 3 —C(O)OR PR , —S—C(O)—(CH 2 ) 4 —C(O)OH, —S—C(O)—(CH 2 ) 5 —C(O)OH, —S—C(O)—(CH 2 ) 5 —C(O)OR PR , —S—C(O)—(CH 2 ) 4 —C(O)OR PR , —S—C(O)—CH(NH 2 )—CH 2 OH, —S—C(O)—CH 2 —N(CH 3 )—C(═NH)—NH 2 , —S—C(O)—CH 2 —NH—C(O)—CH(CH 2 SH)—NH—C(O)—(CH 2 ) 2 —CH(NH 2 )—C(O)—OH), a C2-C20 such as —S—C(O)—CH 3 , —S—C(O)—CF 3 , —S—C(O)—CCl 3 , —S—C(O)—C 2 H 5 , —S—C(O)—C 6 H 5 , —S—C(O)—C 6 H 4 —OCH 3 , —S—C(O)—C 6 H 4 —F, —S—C(O)—C 6 H 4 —Cl, —S—C(O)—C 6 H 4 —CH 3 , —S—C(O)—C 1-12 optionally substituted alkyl, —S—C(O)—CH 2 —NHR PR , —S—C(O)—CHOH—NHR PR , —S—C(O)—CH[(CH(OH)(CH 3 )]—NHR PR , —S—C(O)—CH(CH 3 )—NHR PR , —S—C(O)—CH[(CH 2 ) 2 C(O)OR PR ]—NHR PR , —S—C(O)—CH(CH 2 C(O)OR PR —NHR PR , —S—C(O)—CH[(CH 2 ) 4 NHR PR ]—NHR PR , —S—C(O)—CH[(CH 2 ) 2 C(O)NHR PR ]—NHR PR , —S—C(O)—CH(CH 2 C(O)NHR PR )—NHR PR , —S—C(O)—(CH 2 ) m —C(O)ON(R PR ) 2 , —S—C(O)—(CH 2 ) m —O—(CH 2 ) m —C(O)OR PR , —S—C(O)—(CH 2 ) m —S—(CH 2 ) m —C(O)OR PR , —S—C(O)—(CH 2 ) m —NR PR —(CH 2 ) m —C(O)OR PR , —S—C(O)—(CH 2 ) m —O—(CH 2 )—C(O)ON(R PR ) 2 , —S—C(O)—(CH 2 )—O—(CH 2 ) m —C(O)O—C1-C10 optionally substituted alkyl, —S—C(O)—(CH 2 ) m —O—(CH 2 ) m —C(O)OR PR , —S—C(O)—(CH 2 ) m —S—(CH 2 ) m —C(O)O—C1-C10 optionally substituted alkyl, —S—C(O)—(CH 2 )—S—(CH 2 ), —C(O)OR PR , —S—C(O)—(CH 2 ) m —NR PR —(CH 2 ), —C(O)O—C1-C10 optionally substituted alkyl, —S—C(O)—(CH 2 ) m —NR PR —(CH 2 ) m —C(O)OR PR , where the optionally substituted alkyl optionally is methyl, ethyl, i-propyl, n-propyl, t-butyl, n-butyl, n-hexyl, n-octyl, n-decyl, vinyl, allyl, phenyl, —CH 2 OH, —CH 2 F, —CF 2 H, —(CH 2 ) n —CH 3 , —(CH 2 ) n —OH, —(CH 2 ) n —F, —(CH 2 ) n —Br, —(CH 2 ) n —NH 2 , —(CH 2 ) n —C(O)—OR PR , —(CH 2 ) n —O—CH 3 , —(CH 2 ) n —S—CH 3 , —(CH 2 ) m —(CH═CH) p —(CH 2 ) q —CH 3 , —(CH 2 ) m —(CH═CH) p —(CH 2 ) q —CH 2 F, —(CH 2 ) m —(CH═CH) p —(CH 2 ) q —CH 2 Br, —(CH 2 ) m —(CH═CH) p (CH 2 ) q —C(O)—OR PR , —(CH 2 ) m —(CH═CH) p —(CH 2 ) q —NHR PR , —CF 3 , —CH 2 CF 3 , —C 2 F 5 , or a thio analog of any ester moiety described herein, wherein R PR independently are —H, a protecting group such as C1-C10 optionally substituted alkyl (e.g., —CH 3 , —C 2 H 5 , —C 3 H 6 OH) or together are a protecting group, n is 1, 2, 3, 4, 5, 6, 7 or 8, m is 0, 1, 2, 3, 4, 5 or 6, p is 0 or 1 and q is 0, 1, 2, 3, 4, 5 or 6, or

thioether, e.g., —SCH 3 , —SC 2 H 5 , —SC 3 H 7 , —SC 4 H 9 , —SC 2 H 3 , —SC 3 H 5 , —SC 4 H 7 , —SCH 2 CH 2 OH, —S—CH 2 —CH(C(O)—NH—CH 2 C(O)OH)—NH—C(O)—(CH 2 ) 2 —CH(NH 2 )—C(O)—OH, —S—(CH 2 ) 2 —N + (CH 3 ) 3 ,), —SCH 2 CH 2 F, —SCH 2 CHF 2 , —SCH 2 CF 3 , —SCH 2 CH 2 Cl, —SCH 2 CH 2 Br, —SCH 2 CH 2 I, —SCH 2 CH 2 CH 2 F, —S—SCH 3 , —S—SC 2 H 5 , —S—SC 3 H 7 , —S—SC 4 H 9 , —S—C 1-20 organic moiety, —S—S—C 1-20 organic moiety, —S—CH 2 —S—C 1-20 organic moiety, —S—(CH 2 ) 2 —S—C 1-20 organic moiety, —S—(CH 2 ) 2 —O—C 1-20 organic moiety, —S—S—CH 3 , —S—S—C 2 H 5 , where the organic moiety is any moiety described herein such as —CH 3 , —C 2 H 5 , i-propyl, n-propyl, t-butyl, n-butyl, n-hexyl, n-octyl, n-decyl, —(CH 2 ) 1-8 —OH, —(CH 2 ) 1-8 —NH 2 , —(CH 2 ) 1-8 —C(O)—OH, —(CH 2 ) 0-3 —(CH═CH) 0-1 —(CH 2 ) 0-3 —CH 3 , —(CH 2 ) 0-3 —(CH═CH) 0-1 —(CH 2 ) 0-3 —CH 2 F, —(CH 2 ) 0-3 —(CH═CH) 0-1 —(CH 2 ) 0-3 —CH 2 Br, —(CH 2 ) 0-3 —(CH═CH) 0-1 —(CH 2 ) 0-3 —C(O)—OR PR , —(CH 2 ) 0-3 —(CH═CH) 0-1 —(CH 2 ) 0-3 —NHR PR , —C(O)—CH 3 —C(O)—C 2 H 5 , —C(O)—C 6 H 5 , —S—C 3-8 alkyl, —S—C 3-8 substituted alkyl, —CF 3 , —CH 2 CF 3 or —C 2 F 5 , wherein R PR is —H or a protecting group, —S—C 1-10 optionally substituted alkyl such as i-propyl, n-propyl, t-butyl, n-butyl, n-hexyl, n-octyl, n-decyl, —(CH 2 ) 1-8 —OH, —(CH 2 ) 1-8 —NH 2 , —(CH 2 ) 1-8 —C(O)—OH, —(CH 2 ) 0-3 —(CH═CH) 0-1 —(CH 2 ) 0-3 —CH 3 , —(CH 2 ) 0-3 —(CH═CH) 0-1 —(CH 2 ) 0-3 —CH 2 F, —(CH 2 ) 0-3 —(CH═CH) 0-1 —(CH 2 ) 0-3 —CH 2 Br, —(CH 2 ) 0-3 —(CH═CH) 0-3 —(CH 2 )—(CH 2 ) 0-3 —(CH═CH) 0-1 —(CH 2 ) 0-3 —NHR PR , —CF 3 , —C 2 F 5 , wherein R PR is —H or a protecting group, or

thioacyl, e.g., —C(S)—(CH 2 ) n —CH 2 OH, —C(S)—(CH 2 ) n —CH 2 F, —C(S)—(CH 2 ) n —CH 2 Cl, —C(S)—(CH 2 ) n —CH 2 Br, —C(S)—CH(CH 3 )—(CH 2 ) 3 —CH(CH 3 ) 2 , —C(S)—CH(CH 3 )—(CH 2 ) n —CH(CH 3 ) 2 , —C(S)—CH(CH 3 )—(CH 2 ) 3 —CH(CH 3 )—CH 2 OH, —C(S)—CH(CH 3 )—(CH 2 ) n —CH(CH 3 )—CH 2 OH, —C(S)—CH(CH 3 )—(CH 2 ) 3 —CH(CH 3 )—CH 2 F, —C(S)—CH(CH 3 )—(CH 2 ) n —CH(CH 3 )—CH 2 F, —C(S)—CH(CH 3 )—(CH 2 ) 3 —CH(CH 3 )—CH 2 Cl, —C(S)—CH(CH 3 )—(CH 2 ) n —CH(CH 3 )—CH 2 Cl, —C(S)CH 3 , —C(S)CH 2 OH, —C(S)CH 2 F, —C(S)CH 2 Cl, —C(S)CH 2 Br, —C(S)-2 furanyl, —C(S)-2 thiophenyl, —C(S)-2 pyrrolyl, —C(S)-2 pyrimidinyl, —C(S)-3 pyrimidinyl, —C(S)-2 pyridyl, —C(S)-3 pyridyl, —C(S)-heterocycle, —C(S)—C1-C20-optionally substituted alkyl or a thio analog of any acyl moiety described herein, where n is 0, 1, 2, 3, 4, 5 or 6, or

optionally substituted amine, e.g., —NH 2 , —NH 3 + Cl − , —NH 3 + Br − , —NH 3 + I − , alkylamine, dialkylamine, —NH—CH 3 , —N(CH 3 ) 2 , —N + (CH 3 ) 3 , —N + (C 2 H 5 ) 3 , —NHOH, —NHR PR —N(R PR ) 2 , —NH—C(O)CH 3 , —NH—C(O)CF 3 , —N(C(O)CF 3 ) 2 , —NH—C(O)CCl 3 , —N(C(O)CCl 3 ) 2 , —NH—C(O)C 6 H 5 , —N(C(O)C 6 H 5 ) 2 , —NH—C 2 H 5 , —N(C 2 H 5 ) 2 , —NH—CH 2 OH, —NH—CH 2 —CH 2 OH, —NH—C 3 H 7 , —N(C 3 H 7 ) 2 , —NH—C(═NH)—N(CH 3 )—CH 2 —C(O)OR PR , —N(CH 3 ) 2 , —N(C 2 H 5 ) 2 , —N(CH 3 )(C 2 H 5 )—N(CH 2 OH)(CH 3 ), —N═C[(CH 2 ) n —H]—OH, —NH—NH—C(O)-optionally substituted alkyl, —NH—C(NH-optionally substituted alkyl)=N-optionally substituted alkyl, —N═C[(CH 2 ) n —H]—O-optionally substituted alkyl, —NH-organic moiety, —NH—C(O)-organic moiety, e.g., —NH—C(O)—CH 3 , —NH—(CH 2 ) n -optionally substituted phenyl, —NH-optionally substituted alkyl, —N(optionally substituted alkyl) 2 , —N(C(O)-optionally substituted alkyl) 2 , —NH—C(O)-optionally substituted alkyl or —NH—(CH 2 ) n -optionally substituted alkyl, wherein any of the phenyl or alkyl moieties are the same or different and are optionally substituted with 1, 2, 3 or more independently selected with substituents described herein, e.g., —O—, —NH—, —S—, —F, —Cl, —Br, —I, —OH, —OR PR , —SH, —SR PR , —CH 3 , —C 2 H 5 , —O—CH 3 , —O—C 2 H 5 , —NO 2 , —CN, —SCN, —NH 2 , —C(O)OR PR or —(CH 2 ) n —C(O)—OR PR , wherein n is 0, 1, 2, 3 or 4, R PR independently or together are —H or a protecting group and the organic moiety is as described herein, e.g., optionally substituted alkyl or an ester, or

optionally substituted amide, e.g., —C(O)—NH 2 , —C(O)—NH—C(CH 3 ) 3 , —C(O)—NH 2 , —C(O)—NH—CH 3 , —C(O)—NH—(CH 2 ) m —CH 3 , —C(O)—NH—(CH 2 ) m —NH 2 , —C(O)—NH—(CH 2 ) m —NHR PR , —C(O)—NH—(CH 2 ) m —NH—(CH 2 ) n —CH 3 , —NH—C(O)H, —NH—C(O)—CH 2 —CH 2 —C(O)OH, —NH—C(O)—CH 2 —CH 2 —C(O)OR PR , —NH—C(O)—(CH 2 ) m —C(O)OH, —NH—C(O)—(CH 2 ) m —C(O)OR PR , —NH—C(O)—CH 3 , —NH—C(O)—(CH 2 ) m —CH 3 , —NH—C(O)—(CH 2 ) m —NH 2 , —NH—C(O)—(CH 2 ) m —NHR PR , —NH—C(O)—O—C(CH 3 ) 3 , —NH—C(O)—O—CH 3 , —NH—C(O)—(CH 2 ) m —NH—(CH 2 ) n —CH 3 , —C(O)—NH-organic moiety, —C(O)—NH-optionally substituted alkyl, —C(O)—NR 49 —(O) p -organic moiety, —C(O)—NH—(O) p —(CH 2 ) n -optionally substituted phenyl, —C(O)—NH—(CH 2 ) n —(O) p -optionally substituted alkyl, —NH—C(O)—(O) p -optionally substituted alkyl, —NH—C(S)—(O) p -optionally substituted alkyl, —NH—C(O)—(S) p -optionally substituted alkyl, wherein 1, 2 or more of any organic, phenyl, alkyl, alkylene, e.g., —(CH 2 )—, —(CH 2 ) m — or —(CH 2 ) n —, methyl, ethyl, n-butyl or t-butyl, moieties are optionally substituted with 1, 2, 3, 4, 5 or more independently selected substituents described herein, e.g., —F, —Cl, —Br, —I, —OH, —CH 3 , —C 2 H 5 , —O—CH 3 , —O—C 2 H 5 , —NO 2 , —CN, —SCN, —NH 2 , —C(O)OR PR or —(CH 2 ) 1-4 —C(O)—OR PR , where R 49 is a protecting group, an organic moiety comprising about 1-10 carbon atoms or R 49 together with the organic moiety is a protecting group and the organic group optionally is optionally substituted alkyl such as i-propyl, n-propyl, t-butyl, n-butyl, n-hexyl, n-octyl, n-decyl, —(CH 2 ) m —OH, —(CH 2 ) m —F, —(CH 2 ) m —Cl, —(CH 2 ) m —Br, —(CH 2 ) m —NH 2 , —(CH 2 ) m —C(O)—OH, —(CH 2 ) m —C(O)—H, —(CH 2 ) m —C(O)—CH 3 , —(CH 2 ) n —(CH═CH) p —(CH 2 ) n —CH 3 , —(CH 2 ) n —(CH═CH) p —(CH 2 ) n —CH 2 F, —(CH 2 ) n —(CH═CH) p —(CH 2 ) n —CH 2 Br, —(CH 2 ) n —(CH═CH) p —(CH 2 ) n —C(O)—OR PR , —(CH 2 ) n —(CH═CH) p —(CH 2 ) n —NHR PR , —CF 3 or —C 2 F 5 , and R PR is —H or a protecting group, optionally substituted alkyl moieties contain 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more carbon atoms and wherein m independently are 1, 2, 3, 4, 5 or 6, n independently are 0, 1, 2, 3 or 4 and p is 0 or 1, or

epoxide or optionally substituted cyclopropyl, when taken together with a hydrogen at an adjacent position on the steroid nucleus, usually where the epoxide or optionally substituted cyclopropyl bonds are both in the α-configuration or the β-configuration, e.g., one or more independently selected epoxide or optionally substituted cyclopropyl ring is present at the 1-2 positions, the 2-3 positions, the 4-5 positions, the 5-6 positions, the 10-11 positions, the 11-12 positions, the 15-16 positions, the 16-17 positions, or at the 2-3 and 16-17 positions of the steroid nucleus, or

—O—Si(C1-C6 alkyl) 3 where each alkyl is independently chosen, e.g., —O—Si(CH 3 ) 3 , —O—Si[C(CH 3 ) 3 ](CH 3 ) 2 , —O—Si[C(CH 3 ) 3 ](C 2 H 5 ) 2 , or

phosphate ester, phosphoester, or an ether or thioether derivative thereof, e.g., —O—P(O)(OH)—OCH 3 , —O—P(O)(OH)—OC 2 H 5 , —O—P(O)(OH)—OC 3 H 7 , —O—P(O)(OH)—OCH 2 CH═CH 2 , —O—P(O)(OCH 3 )—OCH 3 , —O—P(O)(OC 2 H 5 )—OC 2 H 5 , —O—P(O)(OH)—O—(CH 2 ) 2 —N + (CH 3 ) 3 , —O—P(O)(OH)—O—(CH 2 ) 2 —NH 2 ), —O—P(O)(OH)—OH, —O—P(O)(OH)—SH, —O—P(O)(OR PR )—OH, —O—P(O)(OR PR )—SH, —S—P(O)(OH)—OH, —O—P(O)(OH)—S—(CH 2 ) 2 —NH—(CH 2 ) 3 —NH 2 , —O—P(O)(OH)—O—CH 3 , —O—P(O)(OCH 3 ) 2 , —O—P(O)(OH)—O—C 2 H 5 , —O—P(O)(OC 2 H 5 ) 2 , —O—P(O)(OH)—O—C 3 H 7 , —O—P(O)(OC 3 H 7 ) 2 , —O—P—(O)(OH)—O—CH 2 —CH(O—C(O)—(CH 2 ) y (CH═CH) q (CH 2 ) y —CH 3 )—CH 2 —O—C(O)—(CH 2 ) y (CH═CH) q (CH 2 ) y —CH 3 , —O—P—(O)(OH)—O—CH 2 —CH(O—C(O)—(CH 2 ) x CH 3 )—CH 2 —O—C(O)—(CH 2 ) x CH 3 ), —O—P—(O)(OH)—O—CH 2 —CH(O—C(O)—(CH 2 ) 14 CH 3 )—CH 2 —O—C(O)—(CH 2 ) 14 CH 3 ), —O—P—(O)(OH)—O—CH 2 —CH(O—C(O)—(CH 2 ) 12 CH 3 )—CH 2 —O—C(O)—(CH 2 ) 12 CH 3 ), —O—P(O)(OH)—O-optionally substituted alkyl, —S—P(O)(OH)—O-optionally substituted alkyl, —O—P(O)(OH)—S-optionally substituted alkyl, —O—P(O)(O-optionally substituted alkyl)-O-optionally substituted alkyl, —S—P(O)(O-optionally substituted alkyl)-O-optionally substituted alkyl, —O—P(O)(O-optionally substituted alkyl)-S-optionally substituted alkyl, where the optionally substituted alkyl moieties are as described herein and are independently selected, e.g., i-propyl, n-propyl, t-butyl, n-butyl, n-hexyl, n-octyl, n-decyl, —(CH 2 ) m —OH, —(CH 2 ) m —F, —(CH 2 ) m —Cl, —(CH 2 ) m —Br, —(CH 2 ) m —NH 2 , —(CH 2 ) m —C(O)—OH, —(CH 2 ) m —C(O)—H, —(CH 2 ) m —C(O)—CH 3 , —(CH 2 ) n —(O) p —(CH 2 ) n —CH 3 , —(CH 2 ) n —(O) p —(CH 2 ) n —CH 2 OH, —(CH 2 ) n —(CH═CH) p —(CH 2 ) n —CH 3 , —(CH 2 ) n —(CH═CH) p —(CH 2 ) n —CH 2 OH, —(CH 2 ) n —(CH═CH) p —(CH 2 ) n —CH 2 F, —(CH 2 ) n —(CH═CH) p —(CH 2 ) n —CH 2 Br, —(CH 2 ) n —(CH═CH) p (CH 2 ) n —C(O)—OR PR — (CH 2 ) n —(CH═CH) p —(CH 2 ) n —NHR PR , —(CH 2 ) n —(C≡C) p —(CH 2 ) n —CH 3 , —(CH 2 ) n —(C≡C) p —(CH 2 ) n —CH 2 OH, —(CH 2 ) n —(C≡C) p —(CH 2 ) n —CH 2 F, —(CH 2 ) n —(C≡C) p —(CH 2 ) n —CH 2 Br, —(CH 2 ) n —(C≡C) p (C(CH 2 ) n —(C≡C) p —(CH 2 ) n —NHR PR , —CF 3 or —C 2 F 5 , wherein R PR is —H or a protecting group, m is 1, 2, 3, 4, 5 or 6, n independently are 0, 1, 2, 3, 4, 5 or 6 and p is 0 or 1, q is 0 or 1, x independently are 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16 or 17, y independently are 0, 1, 2, 3, 4, 5, 6, 7, 8 or 9 and substituents bonded at double bonds are in the cis, trans or mixed cis and trans configuration, wherein In some embodiments, both n and p are 1 or p is 1 and both n are 2 or one n is 1, the other n is 2 and p is 1, or

thionoester, e.g., a C2-C20 thionoester such as —O—C(S)—CH 3 , —O—C(S)—CF 3 , —O—C(S)—C 2 H 5 or —O—C(S)—C 1-12 optionally substituted alkyl where the optionally substituted alkyl optionally is i-propyl, n-propyl, t-butyl, n-butyl, n-hexyl, n-octyl, n-decyl, vinyl, allyl, phenyl, —CH 2 OH, —CH 2 F, —CF 2 H, —(CH 2 ) n —CH 3 , —(CH 2 ) n —OH, —(CH 2 ) n —F, —(CH 2 ) n —Br, —(CH 2 ) n —NH 2 , —(CH 2 ) n —C(O)—OR PR , —(CH 2 ) n —O—CH 3 , —(CH 2 ) n —S—CH 3 , —(CH 2 ) m —(CH═CH) p —(CH 2 ) q —CH 3 , —(CH 2 ) m —(CH═CH) p —(CH 2 ) q —CH 2 F, —(CH 2 ) m —(CH═CH) p —(CH 2 ) q —CH 2 Br, —(CH 2 ) m —(CH═CH) p —(CH 2 ) q —C(O)—OR PR , —(CH 2 ) m —(CH═CH) p —(CH 2 ) q —NHR PR , —CF 3 , —CH 2 CF 3 or —C 2 F 5 , wherein R PR is —H or a protecting group, n is 1, 2, 3, 4, 5, 6, 7 or 8, m is 0, 1, 2, 3, 4, 5 or 6, p is 0 or 1 and q is 0, 1, 2, 3, 4, 5 or 6, or

amino acid or peptide, e.g., a dipeptide, —O—C(O)—CH 2 —NHR PR , —O—C(O)—CHOH—NHR PR , —O—C(O)—CH[(CH(OH)(CH 3 )]—NHR PR , —O—C(O)—CH(CH 3 )—NHR PR , —O—C(O)—CH[(CH 2 ) 2 C(O)OR PR ]—NHR PR , —O—C(O)—CH(CH 2 C(O)OR PR —NHR PR , —O—C(O)—CH[(CH 2 ) 4 NHR PR ]—NHR PR , —O—C(O)—CH[(CH 2 ) 2 C(O)NHR PR ]—NHR PR , —O—C(O)—CH(CH 2 C(O)NHR PR )—NHR PR , —O—C(O)—CHR 42 —NHR PR , —NH—(CH 2 ) 1-4 —C(O)OR 46 or —O—C(O)—(CH 2 ) 1-4 —NHR 47 where R 42 is —H, —CH 3 , —C 2 H 5 , —(CH 2 ) n —C(O)—OR PR , —CH 2 —C(O)—OH, —CH 2 —C(O)—NHR PR , —CH 2 F, —CH 2 Cl, —CH 2 Br, —CHOH—CH 3 or —CH 2 OH, R 46 is —H, optionally substituted alkyl (e.g., —CH 3 , —C 2 H 5 , —C 2 H 3 , —C 3 H 7 , —C 3 H 5 , —(CH 2 ) 1-8 —OH, —(CH 2 ) 1-8 —NH 2 , —(CH 2 ) 1-8 —C(O)—OH, —(CH 2 ) 0-3 —(CH═CH) 0-1 —(CH 2 ) 0-3 —CH 3 , —(CH 2 ) 0-3 —(CH═CH) 0-1 —(CH 2 ) 0-3 —CH 2 F, —(CH 2 ) 0-3 —(CH═CH) 0-1 —(CH 2 ) 0-3 —CH 2 Br, —(CH 2 ) 0-3 —(CH═CH) 0-1 —(CH 2 ) 0-3 —C(O)—OH, —(CH 2 ) 0-3 —(CH═CH) 0-1 —(CH 2 ) 0-3 —NH 2 , —CF 3 or —C 2 F 5 ) or a protecting group (e.g., t-butyl, phenyl, benzyl or substituted phenyl), R 47 is —H, optionally substituted alkyl (e.g., —CH 3 , —C 2 H 5 , —C 2 H 3 , —C 3 H 7 , —C 3 H 5 , —(CH 2 ) 1-8 —OH, —(CH 2 ) 1-8 —NH 2 , —(CH 2 ) 1-8 —C(O)—OH, —(CH 2 ) 0-3 —(CH═CH) 0-1 —(CH 2 ) 0-3 —CH 3 , —(CH 2 ) 0-3 —(CH═CH) 0-1 —(CH 2 ) 0-3 —CH 2 F, —(CH 2 ) 0-3 —(CH═CH) 0-1 —(CH 2 ) 0-3 —CH 2 Br, —(CH 2 ) 0-3 —(CH═CH) 0-1 —(CH 2 ) 0-3 —C(O)—OH, —(CH 2 ) 0-3 —(CH═CH) 0-1 —(CH 2 ) 0-3 —NH 2 , —CF 3 or —C 2 F 5 ) or a protecting group (e.g., t-butyl, phenyl, benzyl or substituted phenyl) and R PR is —H or an independently selected protecting group such as C1-C8 optionally substituted alkyl and n is 0, 1, 2, or 3, or

optionally substituted heterocycle or —O—[C(O)] m —(CH 2 ) n -optionally substituted heterocycle, —(CH 2 ) n -optionally substituted heterocycle, e.g., 2-pyridyl, 3-pyridyl, 4-pyridyl, 5-pyridyl, 6-pyridyl, 3-pyridazinyl, 4-pyridazinyl, 5-pyridazinyl, 6-pyridazinyl, 2-pyrimidinyl, 4-pyrimidinyl, 5-pyrimidinyl, 6-pyrimidinyl, 2-pyrazinyl, 3-pyrazinyl, 5-pyrazinyl, 6-pyrazinyl, 2-thiazolyl, 4-thiazolyl, 5-thiazolyl, 1-aziridyl, 1-azetedyl, 1-pyrrolyl, 1-imidazolyl, 1-pyrazolyl or 1-piperidinyl, wherein m is 0 or 1 and n is 0, 1, 2 or 3,e.g., m and n are both 0, m is 1 and n is 0, m is 0 and n is 1, m and n are both 1, or

carboxyl which is optionally substituted, e.g., —C(O)OH, —C(O)OR PR , —C(O)OM, —C(O)O—CH 3 , —C(O)—O—(CH 2 ) n —CH 3 , —C(O)—O—CH(CH 3 )—(CH 2 ) n —CH 3 , —C(O)—O—C(CH 3 ) 2 —(CH 2 ) n —CH 3 , —C(O)—O—(CH 2 ) n —C(O)OR PR , —C(O)—O—CH(CH 3 )—(CH 2 ) n —C(O)OR PR , —C(O)—O—C(CH 3 ) 2 —(CH 2 ) n —C(O)—O—(CH 2 ) n —CH 2 OR PR , —C(O)—O—CH(CH 3 )—(CH 2 ) n —CH 2 OR PR , —C(O)—O—C(CH 3 ) 2 —(CH 2 ) n —CH 2 OR PR , —C(O)—O—(CH 2 ) n —CH 2 NHR PR , —C(O)—O—CH(CH 3 )—(CH 2 ) n —CH 2 NHR PR , —C(O)—O—C(CH 3 ) 2 —(CH 2 ) n —(CH 2 ) n —CH 2 NHR PR , —C(O)—O—(CH 2 ) n —CH 2 SR PR , —C(O)—O—CH(CH 3 )—(CH 2 ) n —CH 2 SR PR , —C(O)—O—C(CH 3 ) 2 —(CH 2 ) n —CH 2 SR PR , —C(O)O-organic moiety, —C(O)O—(CH 2 ) n -optionally substituted phenyl or —C(O)O—(CH 2 ) n -optionally substituted alkyl, wherein the phenyl or alkyl moieties are optionally substituted with 1, 2 or 3 independently selected with substituents described herein, e.g., —F, —Cl, —Br, —I, —OH, —CH 3 , —C 2 H 5 , —O—CH 3 , —O—C 2 H 5 , —NO 2 , —CN, —SCN, —NH 2 , —C(O)OR PR or —(CH 2 ) 1-4 —C(O)—OR PR , where n is 0, 1, 2, 3, 4, 5 or 6, R PR is —H or a protecting group such as methyl, ethyl, propyl or butyl, and M is a metal such as an alkali metal, e.g., Li + , Na + or K + or M is another counter ion such as an ammonium ion, or

carbonate, e.g., —O—C(O)—O—CH 3 , —O—C(O)—O—(CH 2 ) n —CH 3 , —O—C(O)—O—CH(CH 3 )—(CH 2 ) n —CH 3 , —O—C(O)—O—CH 2 -halogen, —O—C(O)—O—(CH 2 ) n —CH 2 -halogen, —O—C(O)—O—CH(CH 3 )—(CH 2 ) n —CH 2 -halogen, —O—C(O)—O—C(CH 3 ) 2 —(CH 2 ) n —CH 3 , —O—C(O)—O—(CH 2 ) n —C(O)OR PR , —O—C(O)—O—CH(CH 3 )(CH 2 ) n C(O)OR PR , —O—C(O)—O—C(CH 3 ) 2 —(CH 2 ) n —C(O)OR PR , —C(O)—OR PR , —O—C(O)—O—CH(CH 3 )—(CH 2 ) n —CH 2 OR PR , —O—C(O)—O—C(CH 3 ) 2 —O—C(O)—O—C(CH 3 ) 2 —(CH 2 ) n —CH 2 NHR PR , —O—C(O)—O—CH(CH 3 )—(CH 2 ) n —CH 2 SR PR , —O—C(O)—O—C(CH 3 ) 2 —(CH 2 ) n —CH 2 SR PR , —O—C(O)—O-organic moiety, —O—C(O)—O(CH 2 ) n -optionally substituted phenyl or —C(O)—O—(CH 2 ) n -optionally substituted alkyl, wherein the phenyl or alkyl moieties are optionally substituted with 1, 2 or 3, 4 or more independently selected with substituents described herein, e.g., —F, —Cl, —Br, —I, —OH, —CH 3 , —C 2 H 5 , —O—CH 3 , —O—C 2 H 5 , —NO 2 , —CN, —SCN, —NH 2 , —C(O)OR PR or —(CH 2 ) 1-4 —C(O)—OR PR , and wherein n is 0, 1, 2, 3, 4, 5 or 6 and R PR is —H or a protecting group, or

carbamate, e.g., —O—C(O)—NH 2 , —O—C(O)—NH—CH 3 , —O—C(O)—NH—C 2 H 5 , —O—C(O)—NH—C 3 H 7 , —O—C(O)—NH—C 4 H 9 , —O—C(O)—NH—C 2 H 3 , —O—C(O)—NH—C 3 H 5 , —O—C(O)—NH—C 4 H 7 , —O—C(O)—NHR PR , —O—C(O)—N[(CH 2 ) n CH 3 ]—CH 3 , —O—C(O)—N[(CH 2 ) n CH 3 ]—C 2 H 5 , —O—C(O)—N[(CH 2 ) n CH 3 ]—C 3 H 7 , —O—C(O)—N[(CH 2 ) n CH 3 ]—C 4 H 9 , —O—C(O)—N[(CH 2 ) n CH 3 ]—C 2 H 3 , —O—C(O)—N[(CH 2 ) n CH 3 ]—C 3 H 5 , —O—C(O)—N[(CH 2 ) n CH 3 ]—C 4 H 7 , —O—C(O)—NH-organic moiety, —O—C(O)—NR 48 -organic moiety, —NH—C(O)—O-organic moiety, —NR 48 —C(O)—O-organic moiety, wherein the organic moiety is as described herein, e.g., it optionally comprises about 1-20 carbon atoms, and wherein R 48 is —H, a protecting group, an organic moiety or R 48 together with the organic moiety is a protecting group and the organic moiety optionally is optionally substituted alkyl such as i-propyl, n-propyl, t-butyl, n-butyl, n-hexyl, n-octyl, n-decyl, —(CH 2 ) m —OH, —(CH 2 ) m —F, —(CH 2 ) m —Cl, —(CH 2 ) m —Br, —(CH 2 ) m —NH 2 , —(CH 2 ) m —C(O)—OH, —(CH 2 ) m —C(O)—H, —(CH 2 ) m —C(O)—CH 3 , —(CH 2 ) n —(O) p —(CH 2 ) n —CH 3 , —(CH 2 ) n —(O) p —(CH 2 ) n —CH 2 OH, —(CH 2 ) n —(CH═CH) p —(CH 2 ) n —CH 3 , —(CH 2 ) n —(CH═CH) p —(CH 2 ) n —CH 2 OH, —(CH 2 ) n —(CH═CH) p —(CH 2 ) n —CH 2 F, —(CH 2 ) n —(CH═CH) p —(CH 2 ) n —CH 2 Br, —(CH 2 ) n —(CH═CH) p —(CH 2 ) n —C(O)—OR PR —(CH 2 ) n —(CH═CH) p —(CH 2 ) n —NHR PR , —(CH 2 ) n —(C≡C) p —(CH 2 ) n —CH 3 , —(CH 2 ) n —(C≡C) p —(CH 2 ) n —CH 2 OH, —(CH 2 ) n —(C≡C) p —(CH 2 ) n —CH 2 F, —(CH 2 ) n —(C≡C) p —(CH 2 ) n —CH 2 Br, —(CH 2 ) n —(C≡C) p —(CH 2 ) n —C(O)—OR PR , —(CH 2 ) n —(C≡C) p —(CH 2 ) n —NHR PR , —CF 3 or —C 2 F 5 , wherein R PR is —H or a protecting group, m is 1, 2, 3, 4, 5 or 6, n independently are 0, 1, 2, 3, 4, 5 or 6 and p is 0 or 1, e.g., both n and p are 1 or p is 1 and both n are 2 or one n is 1, the other n is 2 and p is 1, or

phosphothioester or thiophosphate or an ether or thioether derivative thereof, e.g., —O—P(S)(OH)—OH, —O—P(S)(OH)—SH, —O—P(S)(OR PR )—OH, —O—P(S)(OR PR )—SH, —S—P(S)(OH)—OH, —O—P(S)(OH)—O—CH 3 , —O—P(S)(OH)—O—C 2 H 5 , —O—P(S)(OH)—O—C 3 H 7 , —O—P(S)(OH)—O-optionally substituted alkyl, —S—P(S)(OH)—O-optionally substituted alkyl, —O—P(S)(OH)—S-optionally substituted alkyl, —O—P(S)(O-optionally substituted alkyl)-O-optionally substituted alkyl, —S—P(S)(O-optionally substituted alkyl)-O-optionally substituted alkyl, —O—P(S)(O-optionally substituted alkyl)-S-optionally substituted alkyl, where the optionally substituted alkyl moieties are as described herein and are independently selected, e.g., i-propyl, n-propyl, t-butyl, n-butyl, n-hexyl, n-octyl, n-decyl, —(CH 2 ) m —OH, —(CH 2 ) m —F, —(CH 2 ) m —Cl, —(CH 2 ) m —Br, —(CH 2 ) m —NH 2 , —(CH 2 ) m —C(O)—OH, —(CH 2 ) m —C(O)—H, —(CH 2 ) m —C(O)—CH 3 , —(CH 2 ) n —(O) p —(CH 2 ) n —CH 3 , —(CH 2 ) n —(O) p —(CH 2 ) n —CH 2 OH, —(CH 2 ) n —(CH═CH) p —(CH 2 ) n —CH 3 , —(CH 2 ) n —(CH═CH) p —(CH 2 ) n —CH 2 OH, —(CH 2 ) n —(CH═CH) p —(CH 2 ) n —CH 2 F, —(CH 2 ) n —(CH═CH) p —(CH 2 ) n —CH 2 Br, —(CH 2 ) n —(CH═CH) p —(CH 2 ) n —C(O)—OR PR , —(CH 2 ) n —(CH═CH) p —(CH 2 ) n —NHR PR , —(CH 2 ) n —(C≡C) p —(CH 2 ) n —CH 3 , —(CH 2 ) n —(C≡C) p —(CH 2 ) n —CH 2 OH, —(CH 2 ) n —(C≡C) p —(CH 2 ) n —CH 2 F, —(CH 2 ) n —(C≡C) p —(CH 2 ) n —CH 2 Br, —(CH 2 ) n —(C≡C) p —(CH 2 ) n —C(O)—OR PR , —(CH 2 ) n —(C≡C) p —(CH 2 ) n —NHR PR , —CF 3 or —C 2 F 5 , wherein R PR is —H or a protecting group, m is 1, 2, 3, 4, 5 or 6, n independently are 0, 1, 2, 3, 4, 5 or 6 and p is 0 or 1, e.g., both n and p are 1 or p is 1 and both n are 2 or one n is 1, the other n is 2 and p is 1, or

phosphonoester, phosphonate or an ether or thioether derivative thereof, e.g., —P(O)(OH)—OH, —P(O)(OH)—SH, —P(O)(OR PR )—OH, —P(O)(OR PR )—SH, —P(O)(OH)—OH, —P(O)(OH)—O—CH 3 , —P(O)(OH)—O—C 2 H 5 , —P(O)(OH)—O—C 3 H 7 , —O—P(O)(OH)—H, —S—P(O)(OH)—H, —O—P(O)(OR PR )—H, —S—P(O)(OR PR )—H, —O—P(O)(OH)—CH 3 , —O—P(O)(OH)—C 2 H 5 , —O—P(O)(OH)—C 3 H 7 , —O—P(O)(OH)-optionally substituted alkyl, —S—P(O)(OH)-optionally substituted alkyl, —P(O)(OH)—O-optionally substituted alkyl, —P(O)(OH)—S-optionally substituted alkyl, —P(O)(O-optionally substituted alkyl)-O-optionally substituted alkyl, —P(O)(O-optionally substituted alkyl)-S-optionally substituted alkyl, where the optionally substituted alkyl moieties are as described herein and are independently selected, e.g., i-propyl, n-propyl, t-butyl, n-butyl, n-hexyl, n-octyl, n-decyl, —(CH 2 ) m —OH, —(CH 2 ) m —F, —(CH 2 ) m —Cl, —(CH 2 ) m —Br, —(CH 2 ) m —NH 2 , —(CH 2 ) m —C(O)—OH, —(CH 2 ) m —C(O)—H, —(CH 2 ) m —C(O)—CH 3 , —(CH 2 ) n —(O) p —(CH 2 ) n —CH 3 , —(CH 2 ) n —(O) p —(CH 2 ) n —CH 2 OH, —(CH 2 ) n —(CH═CH) p —(CH 2 ) n —CH 3 , —(CH 2 ) n —(CH═CH) p —(CH 2 ) n —CH 2 OH, —(CH 2 ) n —(CH═CH) p —(CH 2 ) n —CH 2 F, —(CH 2 ) n —(CH═CH) p —(CH 2 ) n —CH 2 Br, —(CH 2 ) n —(CH═CH) p —(CH 2 ) n —C(O)—OR PR , —(CH 2 ) n —(CH═CH) p —(CH 2 ) n —NHR PR , —(CH 2 ) n —(C≡C) p —(CH 2 ) n —CH 3 , —(CH 2 ) n —(C≡C) p —(CH 2 ) n —CH 2 OH, —(CH 2 ) n —(C≡C) p —(CH 2 ) n —CH 2 F, —(CH 2 ) n —(C≡C) p —(CH 2 ) n —CH 2 Br, —(CH 2 ) n —(C≡C) p —(CH 2 ) n —C(O)—OR PR , —(CH 2 ) n —(C≡C) p —(CH 2 ) n —NHR PR , —CF 3 or —C 2 F 5 , wherein R PR is —H or a protecting group, m is 1, 2, 3, 4, 5 or 6, n independently are 0, 1, 2, 3, 4, 5 or 6 and p is 0 or 1, e.g., both n and p are 1 or p is 1 and both n are 2 or one n is 1, the other n is 2 and p is 1, or

sulfate ester or an ether or thioether derivative thereof, e.g., —O—S(O)(O)—OH, —O—S(O)(O)—SH, —O—S(O)(O)—OR PR , —O—S(O)(O)—O—CH 3 , —O—S(O)(O)—O—C 2 H 5 , —O—S(O)(O)—O—C 3 H 7 , —O—S(O)(O)—S—CH 3 , —O—S—(O)(O)—O—CH 2 —CH(O—C(O)—(CH 2 ) y (CH═CH) q (CH 2 ) y —CH 3 )—CH 2 —O—C(O)—(CH 2 ) y (CH═CH) q (CH 2 ) y —CH 3 , —O—S—(O)(O)—O—CH 2 —CH(O—C(O)—(CH 2 ) x CH 3 )—CH 2 —O—C(O)—(CH 2 ) x CH 3 ), —O—S—(O)(O)—O—CH 2 —CH(O—C(O)—(CH 2 ) 14 CH 3 )—CH 2 —O—C(O)—(CH 2 ) 14 CH 3 ), —O—S—(O)(O)—O—CH 2 —CH(O—C(O)—(CH 2 ) 12 CH 3 )—CH 2 —O—C(O)—(CH 2 ) 12 CH 3 ), —O—S(O)(O)—O-optionally substituted alkyl, —O—S(O)(OH)—S-optionally substituted alkyl, where the optionally substituted alkyl moiety is as described herein, e.g., i-propyl, n-propyl, t-butyl, n-butyl, n-hexyl, n-octyl, n-decyl, —(CH 2 ) m —OH, —(CH 2 ) m —F, —(CH 2 ) m —Cl, —(CH 2 ) m —Br, —(CH 2 ) m —NH 2 , —(CH 2 ) m —C(O)—OH, —(CH 2 ) m —C(O)—H, —(CH 2 ) m —C(O)—CH 3 , —(CH 2 ) n —(O) p —(CH 2 ) n —CH 3 , —(CH 2 ) n —(O) p —(CH 2 ) n —CH 2 OH, —(CH 2 ) n —(CH═CH) p —(CH 2 ) n —CH 3 , —(CH 2 ) n —(CH═CH) p —(CH 2 ) n —CH 2 OH, —(CH 2 ) n —(CH═CH) p —(CH 2 ) n —CH 2 F, —(CH 2 ) n —(CH═CH) p —(CH 2 ) n —CH 2 Br, —(CH 2 ) n —(CH═CH) p —(CH 2 ) n —C(O)—OR PR , —(CH 2 ) n —(CH═CH) p —(CH 2 ) n —NHR PR , —(CH 2 ) n —(C≡C) p —(CH 2 ) n —CH 3 , —(CH 2 ) n —(C≡C) p —(CH 2 ) n —CH 2 OH, —(CH 2 ) n —(C≡C) p —(CH 2 ) n —CH 2 F, —(CH 2 ) n —(C≡C) p —(CH 2 ) n —CH 2 Br, —(CH 2 ) n —(C≡C) p —(CH 2 ) n —C(O)—OR PR , —(CH 2 ) n —(C≡C) p —(CH 2 ) n —NHR PR , —CF 3 or —C 2 F 5 , wherein R PR is —H or a protecting group, m is 1, 2, 3, 4, 5 or 6, n independently are 0, 1, 2, 3, 4, 5 or 6, p is 0 or 1, q is 0 or 1, x independently are 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16 or 17, y independently are 0, 1, 2, 3, 4, 5, 6, 7, 8 or 9 and substituents bonded at double bonds are in the cis, trans or mixed cis and trans configuration, wherein In some embodiments, both n and p are 1 or p is 1 and both n are 2 or one n is 1, the other n is 2 and p is 1, or

optionally substituted oxime, e.g., ═NOH, ═NOCH 3 , ═NOC 2 H 5 , ═NOC 3 H 7 , ═N—(CH 2 ) n —(X) q —(CH 2 ) n -optionally substituted alkyl, where X is —O—, —C(O)—, —S— or —NH— and the optionally substituted alkyl moiety is as described herein, e.g., i-propyl, n-propyl, t-butyl, n-butyl, n-hexyl, n-octyl, n-decyl, —(CH 2 ) m —OH, —(CH 2 ) m —F, —(CH 2 ) m —Cl, —(CH 2 ) m —Br, —(CH 2 ) m —NH 2 , —(CH 2 ) m —C(O)—OH, —(CH 2 ) m —C(O)—H, —(CH 2 ) m —C(O)—CH 3 , —(CH 2 ) m -heterocycle, —(CH 2 ) n —(O) p —(CH 2 ) n —CH 3 , —(CH 2 ) n —(O) p —(CH 2 ) n —CH 2 OH, —(CH 2 ) n —(CH═CH) p —(CH 2 ) n —CH 3 , —(CH 2 ) n —(CH═CH) p —(CH 2 ) n —CH 2 OH, —(CH 2 ) n —(CH═CH) p —(CH 2 ) n —CH 2 F, —(CH 2 ) n —(CH═CH) p —(CH 2 ) n —CH 2 Br, —(CH 2 ) n —(CH═CH) p —(CH 2 ) n —C(O)—OR PR , —(CH 2 ) n —(CH═CH) p —(CH 2 ) n —NHR PR , —(CH 2 ) n —(C≡C) p —(CH 2 ) n —CH 3 , —(CH 2 ) n —(C≡C) p —(CH 2 ) n —CH 2 OH, —(CH 2 ) n —(C≡C) p —(CH 2 ) n —CH 2 F, —(CH 2 ) n —(C≡C) p —(CH 2 ) n —CH 2 Br, —(CH 2 ) n —(C≡C) p —(CH 2 ) n —C(O)—OR PR , —(CH 2 ) n —(C≡C) p —(CH 2 ) n —NHR PR , —CF 3 or —C 2 F 5 , wherein R PR is —H or a protecting group, m is 1, 2, 3, 4, 5 or 6, n independently are 0, 1, 2, 3, 4, 5 or 6, p is 0 or 1, and q is 0 or 1, e.g., both n and p are 1 or p is 1 and both n are 2 or one n is 1, the other n is 2 and p is 1, or

sulfite ester, sulfite ether, sulfite or sulfoxide, e.g., —O—S(O)—OH, —O—S(O)—OR PR , —O—S(O)—O—CH 3 , —O—S(O)—O—C 2 H 5 , —O—S(O)—O—C 3 H 7 , —O—S(O)—O-organic moiety, —O—S(O)—O-optionally substituted alkyl, —S(O)—O—CH 3 , —S(O)—O—C 2 H 5 , —S(O)—O—C 3 H 7 , —S(O)-organic moiety, —S(O)-optionally substituted alkyl, where the optionally substituted alkyl moiety is as described herein, e.g., i-propyl, n-propyl, t-butyl, n-butyl, n-hexyl, n-octyl, n-decyl, —(CH 2 ) m —OH, —(CH 2 ) m —F, —(CH 2 ) m —Cl, —(CH 2 ) m —Br, —(CH 2 ) m —NH 2 , —(CH 2 ) m —C(O)—OH, —(CH 2 ) m —C(O)—H, —(CH 2 ) m —C(O)—CH 3 , —(CH 2 ) n —(O) p —(CH 2 ) n —CH 3 , —(CH 2 ) n —(O) p —(CH 2 ) n —CH 2 OH, —(CH 2 ) n —(CH═CH) p —(CH 2 ) n —CH 3 , —(CH 2 ) n —(CH═CH) p —(CH 2 ) n —CH 2 OH, —(CH 2 ) n —(CH═CH) p —(CH 2 ) n —CH 2 F, —(CH 2 ) n —(CH═CH) p —(CH 2 ) n —CH 2 Br, —(CH 2 ) n —(CH═CH) p —(CH 2 ) n —C(O)—OR PR , —(CH 2 ) n —(CH═CH) p —(CH 2 ) n —NHR PR , —(CH 2 ) n —(C≡C) p —(CH 2 ) n —CH 3 , —(CH 2 ) n —(C≡C) p —(CH 2 ) n —CH 2 OH, —(CH 2 ) n —(C≡C) p —(CH 2 ) n —CH 2 F, —(CH 2 ) n —(C≡C) p —(CH 2 ) n —CH 2 Br, —(CH 2 ) n —(C≡C) p —(CH 2 ) n —C(O)—OR PR , —(CH 2 ) n —(C≡C) p —(CH 2 ) n —NHR PR , —CF 3 or —C 2 F 5 , wherein R PR is —H or a protecting group, m is 1, 2, 3, 4, 5 or 6, n independently are 0, 1, 2, 3, 4, 5 or 6 and p is 0 or 1, e.g., both n and p are 1 or p is 1 and both n are 2 or one n is 1, the other n is 2 and p is 1, and the organic moiety is as described herein, or

sulfonamide or a sulfonamide derivative, e.g., —S(O)(O)—NH 2 , —S(O)(O)—NHR PR , —S(O)(O)—NH-optionally substituted alkyl, —NH—S(O)(O)-optionally substituted alkyl, —S(O)(O)—NH—CH 3 , —S(O)(O)—NH—C 2 H 5 , —S(O)(O)—NH—C 3 H 7 , —NH—S(O)(O)—CH 3 , —NH—S(O)(O)—C 2 H 5 , —NH—S(O)(O)—C 3 H 7 , where the optionally substituted alkyl moiety is as described herein, e.g., i-propyl, n-propyl, t-butyl, n-butyl, n-hexyl, n-octyl, n-decyl, —(CH 2 ) m —OH, —(CH 2 ) m —F, —(CH 2 ) m —Cl, —(CH 2 ) m —Br, —(CH 2 ) m —NH 2 , —(CH 2 ) m —C(O)—OH, —(CH 2 ) m —C(O)—H, —(CH 2 ) m —C(O)—CH 3 , —(CH 2 ) n —(O) p —(CH 2 ) n —CH 3 , —(CH 2 ) n —(O) p —(CH 2 ) n —CH 2 OH, —(CH 2 ) n —(CH═CH) p —(CH 2 ) n —CH 3 , —(CH 2 ) n —(CH═CH) p —(CH 2 ) n —CH 2 OH, —(CH 2 ) n —(CH═CH) p —(CH 2 ) n —CH 2 F, —(CH 2 ) n —(CH═CH) p —(CH 2 ) n —CH 2 Br, —(CH 2 ) n —(CH═CH) p —(CH 2 ) n —C(O)—OR PR , —(CH 2 ) n —(CH═CH) p —(CH 2 ) n —NHR PR , —(CH 2 ) n —(C≡C) p —(CH 2 ) n —CH 3 , —(CH 2 ) n —(C≡C) p —(CH 2 ) n —CH 2 OH, —(CH 2 ) n —(C≡C) p —(CH 2 ) n —CH 2 F, —(CH 2 ) n —(C≡C) p —(CH 2 ) n —CH 2 Br, —(CH 2 ) n —(C≡C) p —(CH 2 ) n —C(O)—OR PR , —(C□C) p —(CH 2 ) n —NHR PR , —CF 3 or —C 2 F 5 , wherein R PR is —H or a protecting group, m is 1, 2, 3, 4, 5 or 6, n independently are 0, 1, 2, 3, 4, 5 or 6 and p is 0 or 1, e.g., both n and p are 1 or p is 1 and both n are 2 or one n is 1, the other n is 2 and p is 1, or

sulfamate or a sulfamate derivative, e.g., —O—S(O)(O)—NH 2 , —O—S(O)(O)—NHR PR , —O—S(O)(O)—N(RD) 2 , —O—S(O)(O)—NH-optionally substituted alkyl, —NH—S(O)(O)—O-optionally substituted alkyl, —O—S(O)(O)—NH—C(O)—CH 3 , —O—S(O)(O)—NH—C(O)-optionally substituted alkyl, —O—S(O)(O)—NH—CH 3 , —O—S(O)(O)—NH—C 2 H 5 , —O—S(O)(O)—NH—C 3 H 7 , —O—S(O)(O)—N(C(O)-optionally substituted alkyl)—R 52 , —O—S(O)(O)—N(C(O)—N-optionally substituted alkyl)—R 52 , —NH—S(O)(O)—O—CH 3 , —NH—S(O)(O)—O—C 2 H 5 , —NH—S(O)(O)—O—C 3 H 7 , —NH—S(O)(O)—O-optionally substituted alkyl, where any optionally substituted alkyl moiety is as described herein, e.g., i-propyl, n-propyl, t-butyl, n-butyl, n-hexyl, n-octyl, n-decyl, —(CH 2 ) m —OH, —(CH 2 ) m —F, —(CH 2 ) m —Cl, —(CH 2 ) m —Br, —(CH 2 ) m —NH 2 , —(CH 2 ) m —C(O)—OH, —(CH 2 ) m —C(O)—H, —(CH 2 ) m —C(O)—CH 3 , —(CH 2 ) n —(O) p —(CH 2 ) n —CH 3 , —(CH 2 ) n —(O) p —(CH 2 ) n —CH 2 OH, —(CH 2 ) n —(CH═CH) p —(CH 2 ) n —CH 3 , —(CH 2 ) n —(CH═CH) p —(CH 2 ) n —CH 2 OH, —(CH 2 ) n —(CH═CH) p —(CH 2 ) n —CH 2 F, —(CH 2 ) n —(CH═CH) p —(CH 2 ) n —CH 2 Br, —(CH 2 ) n —(CH═CH) p —(CH 2 ) n —C(O)—OR PR , —(CH 2 ) n —(CH═CH) p —(CH 2 ) n —NHR PR , —(CH 2 ) n —(C≡C) p —(CH 2 ) n —CH 3 , —(CH 2 ) n —(C≡C) p —(CH 2 ) n —CH 2 OH, —(CH 2 ) n —(C≡C) p —(CH 2 ) n —CH 2 F, —(CH 2 ) n —(C≡C) p —(CH 2 ) n —CH 2 Br, —(CH 2 ) n (C≡C) p —(CH 2 ) n —C(O)OR PR , —(CH 2 ) n —(C≡C) p —(CH 2 ) n —NHR PR , —CF 3 or —C 2 F 5 , wherein R PR is —H or a protecting group, RD independently are —H, optionally substituted alkyl (e.g., —CH 3 , —C 2 H 5 , —C 3 H 7 , —CHO, —CH 2 OH), acyl, benzoyl or benzyl, R 52 is —H, optionally substituted alkyl, —COOH, —COOR PR , —COO-optionally substituted alkyl or —C(O)—N(R 53 ) 2 , R 53 independently are —H, optionally substituted alkyl, optionally substituted aryl, optionally substituted alkylaryl or optionally substituted arylalkyl, or both R 53 together with the nitrogen atom to which they are bonded are an N-containing ring such as morpholino or a C2-C6 polyemthyleneimino residue, m is 1, 2, 3, 4, 5 or 6, n independently are 0, 1, 2, 3, 4, 5 or 6 and p is 0 or 1, e.g., both n and p are 1 or p is 1 and both n are 2 or one n is 1, the other n is 2 and p is 1, or

a sulfonate, a sulfamide, a sulfinamide or a sulfurous diamide, e.g., —O—S(O)(O)—CH 2 -optionally substituted alkyl, —O—S(O)(O)-optionally substituted alkyl, —NH—S(O)(O)—NHR PR , —NH—S(O)(O)—NH-optionally substituted alkyl, —NH—S(O)—NHR PR , —NH—S(O)—NH-optionally substituted alkyl, —S(O)—NHR PR , —S(O)—NHCH 3 , —S(O)—N(CH 3 ) 2 , —S(O)—NHC 2 H 5 , —S(O)—NH-optionally substituted alkyl, —NH—S(O)—NHR PR , —NH—S(O)—NHCH 3 , —NH—S(O)—NHC 2 H 5 or —NH—S(O)—NH-optionally substituted alkyl, or

a monosaccharide, e.g., a D-, L- or DL-mixture of glucose, fructose, mannose, idose, galactose, allose, gulose, altrose, talose, fucose, erythrose, threose, lyxose, erythrulose, ribulose, xylulose, ribose, arabinose, xylose, psicose, sorbose, tagatose, glyceraldehyde, dihydroxyacetone, a monodeoxy derivative of these monosaccharides such as rhamnose, glucuronic acid or a salt of glucuronic acid, any of which are unprotected, partially protected (e.g., less than all hydroxyl groups are protected) or fully protected with independently selected protecting groups (e.g., acetoxy or propionoxy), including moieties such β-D-glucopyranosyl, β-D-glucopyranuronosyl, β-D-2-acetamido-2-deoxy-glucopyranosyl, β-D-galactopyranosyl, β-D-fucopyranosyl, β-L-fucopyranosyl, α-D-fructofuranosyl, β-D-fructofuranosyl, β-D-xylopyranosyl, β-L-xylopyranosyl, α-D-arabanopyranosyl, α-L-arabanopyranosyl, α-L-rhamnopyranosyl, α-D-rhamnopyranosyl, α-D-cellobiosyl, β-D-cellobiosyl, β-D-lactosyl, β-D-maltosyl, β-D-gentiobiosyl, 3-O-β-D-galactopyranosyl-α-D-arabanopyranosyl or β-D-maltotriosyl, any of which are optionally protected and where the variable group to which they are bonded is in the α- or β-configuration, or

an oligosaccharide, e.g., 2, 3, 4 or more linked and independently selected monosaccharides that comprise a D-, L- or DL-mixture of glucose, fructose, mannose, idose, galactose, allose, gulose, altrose, talose, fucose, erythrose, threose, lyxose, erythrulose, ribulose, xylulose, ribose, arabinose, xylose, psicose, sorbose, tagatose, glyceraldehyde, N-acetylglucosamine, dihydroxyacetone or a monodeoxy or dideoxy derivative of any of these, with adjacent monosaccharides having the glycosidic linkage at the anomeric carbon of each monosaccharide unit independently alpha or beta linked, e.g., 1→2, 1→3, 1→4, and/or 1→6 glycosidic bonds in the α- and/or β-configuration, e.g., -glucose-mannose, -glucose-mannose-mannose, -mannose-mannose, -mannose-mannose-man nose, -glucose-galactose, -galactose-glucose, -fructose-galactose, -galactose-fructose, -galactose-galactose, -galactose-mannose, -glucuronic acid-glucose, -glucose-glucose, —(O-1β)-D-glucopyranosyl-(1α-O-4)-D-glucopyranoside, —(O-1β)-tetra-O-acetyl-D-glucopyranosyl-(1β-O-4)-tri-O-acetyl-D-glucopyranoside, —(O-1β)-D-galactopyranosyl-(1β-O-4)-D-glucopyranoside, wherein one or more of the monosaccharides are optionally partially or fully protected, e.g., with —C(O)—CH 3 or —C(O)—C 2 H 5 to protect 1, 2, 3, 4 or more hydroxyl groups, including moieties such α-D-cellobiosyl, β-D-cellobiosyl, β-D-lactosyl, β-D-maltosyl, β-D-gentiobiosyl, 3-O-β-D-galactopyranosyl-α-D-arabanopyranosyl or β-D-maltotriosyl, any of which are optionally protected and where the variable group to which they are bonded is in the α- or β-configuration, or

a glycol or polyethyleneglycol or a derivative, e.g., propylene glycol, ethylene glycol, 1,4-butylene glycol, 1,3-butylene glycol, 1,2-butylene glycol, —O—C(O)—O—(CH 2 CH 2 O) n —H, —C(O)—CH 2 —O—C(O)—O—(CH 2 CH 2 O) n —H or —O—(CH 2 CH 2 O) n —H, where n is 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10, or

an acetal or spiro ring, e.g., —O—CH 2 —O—, —O—(CH 2 ) 2 —O—, —O—(CH 2 ) 3 —O— or —[C(R 36 ) 2 ] 1-4 —O—, —O—C(O)—CH 2 —, —O—C(O)—CH 2 —CH 2 —, —O—C(O)—CH 2 —CH 2 —CH 2 —, —O—C(O)—CHR 10 —, —O—C(O)—CHR 10 —CHR 10 —, —O—C(O)—(CHR 10 ) 3 —, —NH—(CH 2 ) 2 —O—, —NH—(CH 2 ) 2 —NH—, —NH—(CH 2 ) 2 —S—, —CH 2 —N═CH—NH—, —NH—(CH 2 ) 3 —O—, —NH—(CH 2 ) 3 —S—, —NH—(CH 2 ) 3 —O—, where R 10 are independently selected and optionally independently are —H, —F, —Cl, —Br, —I, —CH 3 , —C 2 H 5 , —CF 3 , —C 2 F 5 , —CH 2 CF 3 , —OH, —CN, —SCN, —OCH 3 or —OC 2 H 5 , and where each R 36 independently is —H, —F, —Cl, —Br, —I or an organic moiety such as C1-C10 optionally substituted alkyl (e.g., methyl or ethyl), C2-10 alkenyl, aryl or a heterocycle, any of which are optionally substituted as described herein, e.g., —CF 3 or —CH 2 OH, or

thioacetal, e.g., —S—CH 2 —O—, —S—(CH 2 ) 2 —O—, —S—(CH 2 ) 3 —O—, —S—CH 2 —S—, —S—(CH 2 ) 2 —S—, —S—(CH 2 ) 3 —S— or —S—[C(R 36 ) 2 ] 1-4 —S— where each R 36 independently is —H, —F, —Cl, —Br, —I or an organic moiety such as C1-C10 optionally substituted alkyl (e.g., methyl or ethyl), C2-10 alkenyl, aryl or a heterocycle, any of which are optionally substituted as described herein, e.g., —CF 3 or —CH 2 OH. The salts, ionized forms and solvates of any of these moieties are also included, e.g., where a group such as —NH 2 or —COOH is ionized to generate a moiety such as —NH 3 + Cl − , —NH 3 + Br − , —COO − Na + or —COO − K + .

For any of these exemplary F1C, e.g., the B, C, D, E, F and G structures, some embodiments are characterized by the presence of one or two independently selected substitutions at R 10A , R 10B , R 10C and R 10D and optionally:

(a) R 10E (when present at the 5-position), R 10F , R 10G and R 10H are independently selected R 10 groups in the α,β,α,α or β,β,α,α configurations respectively, R 1 is an oxygen-bonded, nitrogen-bonded or a sulfur-bonded moiety such as —OH, ═O, —SH, ═NOH, —NH(C1-C8 optionally substituted alkyl), an ester, an ether, a thioester, or a thioether, R 1A is —H, absent, a carbon-bonded moiety such as an acyl moiety, optionally substituted alkyl or optionally substituted alkylaryl, R 2 is a halogen or an oxygen-bonded or a sulfur-bonded moiety, R 2A is —H, absent, a carbon-bonded moiety, R 3 is a halogen or an oxygen-bonded or a sulfur-bonded moiety, R 3B is —H, absent, a carbon-bonded moiety, R 4 is a halogen, an oxygen-bonded or a sulfur-bonded moiety, R 4A is —H, absent, a carbon-bonded moiety such as an acyl moiety, optionally substituted alkyl or optionally substituted alkylaryl,

(b) R 10E (if present), R 10F , R 10G and R 10H are independently selected R 10 groups in the α,β,α,α or β,β,α,α configurations respectively, R 1A is —H, an oxygen-bonded, nitrogen-bonded or a sulfur-bonded moiety, R 1 is —H, a carbon-bonded moiety, R 2 is a halogen or an oxygen-bonded or a sulfur-bonded moiety, R 2A is —H, absent, a carbon-bonded moiety, R 3 is a halogen or an oxygen-bonded or a sulfur-bonded moiety, R 3B is —H, absent, a carbon-bonded moiety, R 4 is a halogen, an oxygen-bonded or a sulfur-bonded moiety, R 4A is —H, absent or a carbon-bonded moiety,

(c) R 10E (if present), R 10F , R 10G and R 10H are independently selected R 10 groups in the α,β,α,α or β,β,α,α configurations respectively, R 1 is an oxygen-bonded, nitrogen-bonded or a sulfur-bonded moiety, R 1A is —H, absent or a carbon-bonded moiety, R 2 is a halogen or an oxygen-bonded or a sulfur-bonded moiety, R 2A is —H, absent or a carbon-bonded moiety, R 3 is a halogen or an oxygen-bonded or a sulfur-bonded moiety, R 3B is —H, absent or a carbon-bonded moiety, R 4A is a halogen, an oxygen-bonded or a sulfur-bonded moiety, R 4 is —H, a halogen or a carbon-bonded moiety,

(d) R 10E (if present), R 10F , R 10G and R 10H are independently selected R 10 groups in the α,β,α,α or β,β,α,α configurations respectively, R 1 is an oxygen-bonded, nitrogen-bonded or a sulfur-bonded moiety, R 1A is —H, absent, a carbon-bonded moiety, R 2 is a halogen or an oxygen-bonded or a sulfur-bonded moiety, R 2A is —H, absent or a carbon-bonded moiety, R 3 is a halogen or an oxygen-bonded or a sulfur-bonded moiety, R 3B is —H, absent or a carbon-bonded moiety, R 4 is a halogen, an oxygen-bonded or a sulfur-bonded moiety, R 4A is —H, absent or a carbon-bonded moiety,

(e) R 10E (if present), R 10F , R 10G and R 10H are independently selected R 10 groups in the α,β,α,α or β,β,α,α configurations respectively, R 1 is an oxygen-bonded, nitrogen-bonded or a sulfur-bonded moiety, R 1A is —H, absent or a carbon-bonded moiety, R 2 is a halogen or an oxygen-bonded or a sulfur-bonded moiety, R 2A is —H, absent or a carbon-bonded moiety, R 3B is a halogen or an oxygen-bonded or a sulfur-bonded moiety, R 3 is —H, a carbon-bonded moiety, R 4 is a halogen, an oxygen-bonded or a sulfur-bonded moiety, R 4A is —H, absent or a carbon-bonded moiety,

(f) R 10E (if present), R 10F , R 10G and R 10H are independently selected R 10 groups in the α,β,α,α or β,β,α,α configurations respectively, R 1A is —H, an oxygen-bonded, nitrogen-bonded or a sulfur-bonded moiety, R 1 is —H, a carbon-bonded moiety, R 2 is a halogen or an oxygen-bonded or a sulfur-bonded moiety, R 2A is —H, absent or a carbon-bonded moiety, R 3 is a halogen or an oxygen-bonded or a sulfur-bonded moiety, R 3B is —H, absent or a carbon-bonded moiety, R 4A is a halogen, an oxygen-bonded or a sulfur-bonded moiety, R 4 is —H, a carbon-bonded moiety, or

(g) R 10E (if present), R 10F , R 10G and R 10H are independently selected R 10 groups in the α,β,α,α or β,β,α,α configurations respectively, R 1 is a halogen or an oxygen-bonded, nitrogen-bonded, carbon bonded or a sulfur-bonded moiety, R 1A is —H, a carbon-bonded or nitrogen-bonded moiety and R 2 , R 2A , R 3 R 3B , R 4 and R 4A are as described any of in the foregoing embodiments or elsewhere herein. In any of these embodiments, R 5 -R 9 are independently selected moieties as described herein and the oxygen-bonded, nitrogen-bonded, carbon bonded or sulfur-bonded moieties at R 1 , R 1A , R 2 , R 2A , R 3 , R 3B , R 4 , and R 4A include atoms or groups described herein. These embodiments contain formula B, C, D, E, F and G compounds wherein one or two of R 1 , R 1A , R 2 , R 2A , R 3 , R 3B , R 4 , and R 4A are independently selected nitrogen-bonded moieties, one, two or three of R 1 , R 1A , R 2 , R 2A , R 3 , R 3B , R 4 , and R 4A are independently selected carbon-bonded moieties and one, two, three, four or five of R 2 , R 2A , R 3 , R 3B , R 4 , and R 4A are independently selected or halogen atoms or oxygen-bonded or sulfur-bonded moieties.

These embodiments contain F1C, such as the B, C, D, E, F and G structures wherein R 4 and R 4A are present, i.e., no 16-17 double bond is present, and both are the same, such as optionally substituted alkyl, halogen, ether, ester, thioether, thioester, e.g., —OR PR , —SR PR , —F, —Cl, —Br, —I, methyl, ethyl, methoxy, ethoxy acetate or propionate. However, in many embodiments, when they are both present, R 4 and R 4A are two independently selected dissimilar moieties defined herein, e.g., independently selected —H, —OH, —OR PR , an ester (e.g., —OC(O)—CH 3 , —OC(O)—C 2 H 5 , —OC(O)—C3 alkyl, —OC(O)—C4 alkyl,), ether (e.g., —OCH 3 , —OC 2 H 5 , —OCH 2 CH 2 CH 3 , or —OCH(CH 3 )CH 3 , —O—C4 alkyl, —O—C5 alkyl or —O—C6 alkyl), a thioester, a thioether, an acyl moiety, a carbonate, a carbamate an amide, a monosaccharide, a disaccharide, or an amino acid, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl or another moiety described herein.

For any F1C, examples of dissimilar R 4 and R 4A moieties at the 17-position include (α-ester, β-optionally substituted alkynyl), (β-ester, α-optionally substituted alkynyl), (α-thioester, β-optionally substituted alkynyl), (β-thioester, α-optionally substituted alkynyl), (α-ester, β-optionally substituted alkenyl), (β-ester, α-optionally substituted alkenyl), (α-thioester, β-optionally substituted alkenyl), (β-thioester, α-optionally substituted alkenyl), (α-optionally substituted alkyl, β-ester), (β-optionally substituted alkyl, α-ester), (α-optionally substituted alkyl, β-optionally substituted amine), (β-optionally substituted alkyl, α-optionally substituted amine), (α-optionally substituted alkyl, β-halogen)-, (β-optionally substituted alkyl, α-halogen), (α-halogen, β-ether), (β-halogen, α-ether), (α-halogen, β-optionally substituted alkyl), (β-halogen, α-optionally substituted alkyl), (β-ester, α-acyl), (α-ester, β-acyl), (β-ester, α-C(O)—C1-C10 optionally substituted alkyl), (α-ester, β-C(O)—C1-C10 optionally substituted alkyl), (H-thioester, α-C(O)—C1-C10 optionally substituted alkyl), (α-thioester, β-C(O)—C1-C10 optionally substituted alkyl), (β-OH, α-ester), (α-OH, β-ester), (β-OH, α-ether), (α-OH, β-ether), (β-OH, α-acyl), (α-OH, β-acyl), (α-halogen, β-OR PR ), (β-halogen, α-OR PR ), (α-F, β-ester), (β-F, α-ester), (α-F, β-ether), (β-F, α-ether), (α-Br, β-ether), (β-Br, α-ether), (α-F, β-optionally substituted alkyl), (β-F, α-optionally substituted alkyl), (α-OH, β-optionally substituted alkynyl), (β-OH, α-optionally substituted alkynyl), (α-OH, β-C≡CCH 2 -halogen), (β-OH, α-C≡CCH 2 -halogen), (α-OH, β-C≡C-halogen), (β-OH, α-C≡C-halogen), (β-epoxy, α-halogen, where the epoxy is formed with an adjacent steroid nucleus atom), (α-epoxy, β-halogen), (α-cyclopropyl, β-halogen), (β-cyclopropyl, α-halogen), (α-cyclopropyl, β-optionally substituted alkyl), (β-cyclopropyl, α-optionally substituted alkyl), (α-optionally substituted alkyl, β-NH—C1-C8 optionally substituted alkyl), (β-optionally substituted alkyl, α-NH—C1-C8 optionally substituted alkyl), (α-ether, β-NH—C1-C8 optionally substituted alkyl), (β-ether, α-NH—C1-C8 optionally substituted alkyl), (α-thioester, β-NH—C1-C8 optionally substituted alkyl), (β-thioester, α-NH—C1-C8 optionally substituted alkyl), (α-ester, β-NH—C1-C8 optionally substituted alkyl), (β-ester, α-NH—C1-C8 optionally substituted alkyl), (α-C(O)CH 3 , β-NH—C1-C8 optionally substituted alkyl), (β-C(O)CH 3 , α—NH—C1-C8 optionally substituted alkyl), (α-OH, β-NH—C1-C8 optionally substituted alkyl), (β-OH, α-NH—C1-C8 optionally substituted alkyl) and other combinations of groups that are within the scope of R 4 and R 4A . Such moieties, which are the same or different can also be at 1, 2, 3 or more R 1 and R 1A , R 2 and R 2A , R 3 and R 3B variable groups, and/or the R 10 variable groups at R 7 , R 3 and R 9 .

Specific dissimilar R 4 and R 4A moieties include, e.g., (α-F, β-CH 3 ), (β-F, α-CH 3 ), (α-F, β-C 2 H 5 ), (β-F, α-C 2 H 5 ), (α-Br, β-OCH 3 ), (β-Br, α-OCH 3 ), (α-F, β-OCH 3 ), (β-F, α-OCH 3 ), (α-F, β-OH), (β-F, α-OH), (α-Br, β-OCH 3 ), (β-Br, α-OCH 3 ), (α-F, β-CH 3 ), (β-F, α-CH 3 ), (α-Br, β-CH 3 ), (β-Br, α-CH 3 ), (α-OH, β-CCCH 3 ), (β-OH, α-CCCH 3 ), (α-OH, β-CCCH 2 OH), (β-OH, α-CCCH 2 OH), (α-OH, β-CCH), (β-OH, α-CCH), (α-CH 3 , β-OC(O)CH 3 ), (β-CH 3 , α-OC(O)CH 3 ), (α-C 2 H 5 , β-OC(O)CH 3 ), (β-C 2 H 5 , (α-OC(O)CH 3 ), (α-C 3 H 7 , β-OC(O)CH 3 ), (β-C 3 H 7 , α-OC(O)CH 3 ), (α-C 4 H 9 , β-OC(O)CH 3 ), (β-C 4 H 9 , α-OC(O)CH 3 ), (α-C 2 H 3 , β-OC(O)CH 3 ), (β-C 2 H 3 , α-OC(O)CH 3 ), (α-C 2 H 4 OH, β-OC(O)CH 3 ), (β-C 2 H 4 OH, α-OC(O)CH 3 ), (α-C 3 H 5 , β-OC(O)CH 3 ), (β-C 3 H 5 , (α-OC(O)CH 3 ), (α-C 4 H 7 , β-OC(O)CH 3 ), (β-C 4 H 7 , α-OC(O)CH 3 ), (α-C 3 H 3 , β-OC(O)CH 3 ), (β-C 3 H 3 , (α-OC(O)CH 3 ), (α-C 4 H 5 , β-OC(O)CH 3 ), (β-C 4 H 5 , (β-OC(O)CH 3 ), (α-CH 3 , β-OC(O)C 2 H 5 ), (β-CH 3 , α-OC(O)C 2 H 5 ), (α-C 2 H 5 , β-OC(O)C 2 H 5 ), (β-C 2 H 5 , α-OC(O)C 2 H 5 ), (α-C 3 H 7 , β-OC(O)C 2 H 5 ), (β-C 3 H 7 , α-OC(O)C 2 H 5 ), (α-C 4 H 9 , β-OC(O)C 2 H 5 ), (β-C 4 H 9 , α-OC(O)C 2 H 5 ), (β-C 2 H 3 , β-OC(O)C 2 H 5 ), (β-C 2 H 3 , α-OC(O)C 2 H 5 ), (α-C 2 H 4 OH, β-OC(O)C 2 H 5 ), (β-C 2 H 4 OH, α-OC(O)C 2 H 5 ), (α-C 3 H 5 , β-OC(O)C 2 H 5 ), (β-C 3 H 5 , α-OC(O)C 2 H 5 ), (α-C 4 H 7 , β-OC(O)C 2 H 5 ), (β-C 4 H 7 , α-OC(O)C 2 H 5 ), (α-C 3 H 3 , β-OC(O)C 2 H 5 ), (β-C 3 H 3 , α-OC(O)C 2 H 5 ), (α-C 4 H 5 , β-OC(O)C 2 H 5 ), (β-C 4 H 5 , α-OC(O)C 2 H 5 ), (α-C(O)CH 3 , β-OC(O)CH 3 ), (β-C(O)CH 3 , α-OC(O)CH 3 ), (α-C(O)C 2 H 5 , β-OC(O)CH 3 ), (β-C(O)C 2 H 5 , α-OC(O)CH 3 ), (α-CH 3 , β-SC(O)CH 3 ), (β-CH 3 , α-SC(O)CH 3 ), (α-C 2 H 5 , β-SC(O)CH 3 ), (β-C 2 H 5 , α-SC(O)CH 3 ), (α-C 3 H 7 , P—SC(O)CH 3 ), (β-C 3 H 7 , α-SC(O)CH 3 ), (α-C 4 H 9 , β-SC(O)CH 3 ), (β-C 4 H 9 , α-SC(O)CH 3 ), (α-C 2 H 3 , β-SC(O)CH 3 ), (β-C 2 H 3 , α-SC(O)CH 3 ), (α-C 2 H 4 OH, β-SC(O)CH 3 ), (β-C 2 H 4 OH, α-SC(O)CH 3 ), (α-C 3 H 5 , β-SC(O)CH 3 ), (β-C 3 H 5 , α-SC(O)CH 3 ), (α-C 4 H 7 , β-SC(O)CH 3 ), (β-C 4 H 7 , α-SC(O)CH 3 ), (α-C 3 H 3 , β-SC(O)CH 3 ), (β-C 3 H 3 , α-SC(O)CH 3 ), (α-C 4 H 5 , β-SC(O)CH 3 ), (β-C 4 H 5 , α-SC(O)CH 3 ), (α-CH 3 , β-SC(O)C 2 H 5 ), (β-CH 3 , α-SC(O)C 2 H 5 ), (α-C 2 H 5 , β-SC(O)C 2 H 5 ), (β-C 2 H 5 , α-SC(O)C 2 H 5 ), (α-C 3 H 7 , β-SC(O)C 2 H 5 ), (β-C 3 H 7 , α-SC(O)C 2 H 5 ), (α-C 4 H 9 , β-SC(O)C 2 H 5 ), (β-C 4 H 9 , α-SC(O)C 2 H 5 ), (α-C 2 H 3 , β-SC(O)C 2 H 5 ), (β-C 2 H 3 , α-SC(O)C 2 H 5 ), (α-C 2 H 4 OH, β-SC(O)C 2 H 5 ), (β-C 2 H 4 OH, α-SC(O)C 2 H 5 ), (α-C 3 H 5 , β-SC(O)C 2 H 5 ), (β-C 3 H 5 , α-SC(O)C 2 H 5 ), (α-C 4 H 7 , β-SC(O)C 2 H 5 ), (β-C 4 H 7 , α-SC(O)C 2 H 5 ), (α-C 3 H 3 , β-SC(O)C 2 H 5 ), (β-C 3 H 3 , (α-SC(O)C 2 H 5 ), (α-C 4 H 5 , β-SC(O)C 2 H 5 ), (β-C 4 H 5 , α-SC(O)C 2 H 5 ), (α-C(O)CH 3 , β-SC(O)CH 3 ), (β-C(O)CH 3 , α-SC(O)CH 3 ), (α-C(O)C 2 H 5 , β-SC(O)CH 3 ), (β-C(O)C 2 H 5 , α-SC(O)CH 3 ), (α-C(O)CH 3 , β-NH—CH 3 ), (β-C(O)CH 3 , α-NH—CH 3 ), (α-OH, β-NH—CH 3 ), (β-OH, α-NH—CH 3 ), (α-C(O)CH 3 , β-N(CH 3 ) 2 ), (β-C(O)CH 3 , α-N(CH 3 ) 2 ), (α-OH, β-N(CH 3 ) 2 ), (β-OH, α-N(CH 3 ) 2 ), (α-C(O)CH 3 , β-N(C 2 H 5 ) 2 ), (β-C(O)CH 3 , α-N(C 2 H 5 ) 2 ), (α-OH, β-N(C 2 H 5 ) 2 ), (β-OH, α-N(C 2 H 5 ) 2 ), (β-epoxy, α-H), (α-epoxy, β-H), (β-epoxy, α-Br), (α-epoxy, β-Br), (β-epoxy, α-F), (α-epoxy, β-F), (β-cyclopropyl, α-H), (α-cyclopropyl, β-H), (β-cyclopropyl, α-F) and (α-cyclopropyl, β-F). For moieties that contain an epoxy, cyclopropyl or other cyclic moiety, the cyclic moiety can be formed with an adjacent variable group, e.g., R 3 or R 3B . As is apparent from the foregoing disclosure, these or other dissimilar moieties can also be present at one or more of, e.g., the 2-, 3-, 7-, 11-, 15- or 16-positions.

Additional embodiments of the F1Cs include any F1Cs or any 2, 5, 6, 7, 8, 9, 10, B, C, D, E, F or G structures, e.g., any of the F1Cs or F1C genera disclosed herein, wherein one or both of R 5 or R 6 independently are —H, —CH 2 SH, —CHO, —CH 2 NR PR , —CH 2 NH 2 , —C 4 H 9 , —C 3 H 7 , —C 2 H 5 , —CH 3 , —C 2 H 4 OH, —C 2 H 4 SH, —C 2 H 4 NH 2 , —CH 2 CHO, —CH 2 CH 2 NR PR , —CH 2 CH 2 OH, —CH 2 CH 2 SH, —CH 2 CH 2 C 6 H 5 , —CH 2 C 6 H 5 , —C 6 H 5 or optionally substituted alkyl wherein any phenyl (C 6 H 5 ) moiety in the foregoing groups is optionally substituted at the phenyl ring with 1, 2, 3, 4 or 5 moieties independently selected from those described for esters herein and including C1-C6 alkyl (optionally substituted with 1 or 2 independently selected —OH, —SH, —O—, —S— or —NH—) C1-C6 alkoxy, —F, —Cl, —Br, —I, —CN, —NO 2 , —OH, —SH, —COOR PR , —NHR PR and —C(O)—C1-C6 alkyl. Typically R 5 or R 6 are both in the β-configuration, but they may be in, e.g., the α,β or β,α configurations respectively.

In some embodiments, one or more of the variable groups that are bonded to the F1C, e.g., R 1 -R 5 , R 10 , R 10A , R 10B , R 10C , R 10D , R 15 , R 17 and R 13 , independently are —H, —OH, ═O, —SH, ═S, —SCN, —CN, —NO 2 , —NH 2 , —N 3 , —F, —Cl, —Br, —I, epoxide, —CHO, —CHS, ═CH 2 , ═CH—CH 3 , ═CH—CH 2 OH, ═CH—CH 2 —CH 3 , ═CH—CH(OH)—CH 3 , ═CH—C(O)—CH 3 , ═CH—CH(halogen)-CH 3 , —CH 2 (halogen), —CH(halogen)-CH 3 , —CH 2 —CH(halogen)-CH 3 , —CH 2 —(CH 2 ) n —NH 2 , —CH 2 —(CH 2 ) n —N—H[(CH 2 ) n —CH 3 ], —CH(CH 3 )—NH—(CH 2 ) m —NH 2 , —CH(CH 3 )—NH—(CH 2 ) m —N—H[(CH 2 ) n —CH 3 ], —CH(CH 3 )—NH—(CH 2 ) m —NH(optionally substituted alkyl), —CH(CH 3 )—NH—(CH 2 ) m —N(optionally substituted alkyl) 2 , —CH(CH 3 )—NH—(CH 2 ) 2-3 —N(CH 3 ) 2 , ═NOH, ═NOC(O)CH 3 , ═NOCH 3 , ═NO—CH 2 CH 3 , —C(O)—CH 3 , —C(O)—(CH 2 ) 1-4 —CH 3 , —CCH, —CCCH 3 , —CH═CH 2 , —CH═CH 2 CH 3 , —O—C(O)—(CH 2 ) m —(CF 2 ) n —CH 3 , —O—C(O)—(CH 2 ) m —(CF 2 ) n —CF 3 , —O—C(O)—(CH 2 ) m —(CF 2 ) n —CH 2 F, —O—C(O)—O—(CH 2 ) m —(CF 2 ) n —CH 3 , —O—C(O)—O—(CH 2 ) m —(CF 2 ) n —CF 3 , —O—C(O)—O—(CH 2 ) m —(CF 2 ) n —CH 2 F, —O—C(O)—NH—(CH 2 ) m —(CF 2 ) n —CH 3 , —O—C(O)—NH—(CH 2 ) m —(CF 2 ) n —CF 3 , —O—C(O)—NH—(CH 2 ) m —(CF 2 ) n —CH 2 F (where m is 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10, n is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10, and p is 0, 1 or 2), —CH(CH 3 )—(CH 2 ) 2 —C(O)NH—CH 2 COOH, —CH(CH 3 )—(CH 2 ) 2 —C(O)NH—CH 2 SO 3 H, —OSi(CH 3 ) 2 C(CH 3 ) 3 , —C(OH)═CHCH 3 , ═CH(CH 2 ) 0-15 CH 3 , —(CH 2 ) 0-14 —CH 2 F, —(CH 2 ) 0-14 —CH 2 Cl, —(CH 2 ) 0-14 —CH 2 Br, —(CH 2 ) 0-14 —CH 2 I, —(CH 2 ) 2-10 —O—(CH 2 ) 0-4 —CH 3 , —(CH 2 ) 2-10 —S—(CH 2 ) 0-4 —CH 3 , —(CH 2 ) 2-10 —NH—(CH 2 ) 0-4 —CH 3 , —O—(CH 2 ) 0-14 —CH 2 F, —O—(CH 2 ) 0-14 —CH 2 Cl, —O—(CH 2 ) 0-14 —CH 2 Br, —O—(CH 2 ) 0-14 —CH 2 I, —O—(CH 2 ) 2-10 —O—(CH 2 ) 0-4 —CH 3 , —O—(CH 2 ) 2-10 —S—(CH 2 ) 0-4 —CH 3 , —O—(CH 2 ) 2-10 —NH—(CH 2 ) 0-4 —CH 3 , —O—C(O)—(CH 2 ) 0-14 —CH 2 F, —O—C(O)—(CH 2 ) 0-14 —CH 2 Cl, —O—C(O)—(CH 2 ) 0-14 —CH 2 Br, —O—C(O)—(CH 2 ) 0-14 —CH 2 I, —O—C(O)—(CH 2 ) 2-10 —O—(CH 2 ) 0-4 —CH 3 , —O—C(O)—(CH 2 ) 2-10 —S—(CH 2 ) 0-4 —CH 3 , —O—C(O)—(CH 2 ) 2-10 —NH—(CH 2 ) 0-4 —CH 3 , —O—C(S)—(CH 2 ) 0-14 —CH 2 F, —O—C(S)—(CH 2 ) 0-14 —CH 2 Cl, —O—C(S)—(CH 2 ) 0-14 —CH 2 Br, —O—C(S)—(CH 2 ) 0-14 —CH 2 I, —O—C(S)—(CH 2 ) 2-10 —O—(CH 2 ) 0-4 —CH 3 , —O—C(S)—(CH 2 ) 2-10 —S—(CH 2 ) 0-4 —CH 3 , —O—C(S)—(CH 2 ) 2-10 —NH—(CH 2 ) 0-4 —CH 3 , —(CH 2 ) 0-16 NH 2 , —(CH 2 ) 0-15 CH 3 , —(CH 2 ) 0-15 CN, —(CH 2 ) 0-15 CH═CH 2 , —(CH 2 ) 0-15 NHCH(O), —(CH 2 ) 0-16 NH—(CH 2 ) 0-15 CH 3 , —(CH 2 ) 0-15 CCH, —(CH 2 ) 0-15 OC(O)CH 3 , —(CH 2 ) 0-15 OCH(OH)CH 3 , —(CH 2 ) 0-15 C(O)OCH 3 , —(CH 2 ) 0-15 C(O)OCH 2 CH 3 , —(CH 2 ) 0-15 C(O)(CH 2 ) 0-15 CH 3 , —(CH 2 ) 0-15 C(O)(CH 2 ) 0-15 CH 2 OH, —O(CH 2 ) 1-16 NH 2 , —O(CH 2 ) 1-15 CH 3 , —O(CH 2 ) 1-15 CN, —O(CH 2 ) 1-15 CH═CH 2 , —O(CH 2 ) 1-15 NHCH(O), —O(CH 2 ) 1-16 NH—(CH 2 ) 1-15 CH 3 , —O(CH 2 ) 1-15 CCH, —O(CH 2 ) 1-15 OC(O)CH 3 , —O(CH 2 ) 1-15 OCH(OH)CH 3 , —O(CH 2 ) 1-15 C(O)OCH 3 , —O(CH 2 ) 1-15 C(O)OCH 2 CH 3 , —O(CH 2 ) 1-15 C(O)(CH 2 ) 0-15 CH 3 , —O(CH 2 ) 1-15 C(O)(CH 2 ) 0-15 CH 2 OH, —OC(O)(CH 2 ) 1-16 NH 2 , —OC(O)(CH 2 ) 1-15 CH 3 , —C(O)O(CH 2 ) 1-15 CN, —C(O)O(CH 2 ) 1-15 CH═CH 2 , —OC(O)(CH 2 ) 1-15 NHCH(O), —OC(O)(CH 2 ) 1-16 NH—(CH 2 ) 1-15 CH 3 , —OC(O)(CH 2 ) 1-15 CCH, —OC(O)(CH 2 ) 1-15 OC(O)CH 3 , —OC(O)(CH 2 ) 1-15 OCH(OH)CH 3 , —OC(O)(CH 2 ) 1-15 C(O)OCH 3 , —OC(O)(CH 2 ) 1-15 C(O)OCH 2 CH 3 , —OC(O)(CH 2 ) 1-15 C(O)(CH 2 ) 0-15 CH 3 , —OC(O)(CH 2 ) 1-15 C(O)(CH 2 ) 0-15 CH 2 OH, —C(O)—(CH 2 ) 0, 1, 2, 3, 4, 5, 6 —OPO 3 HR PR , —C(O)—(CH 2 ) 0, 1, 2, 3, 4, 5, 6 —C(O)—C1-C4 optionally substituted alkyl, —O-cyclopentyl, —O—(CH 2 ) 0, 1, 2, 3, 4 —C(O)—CH═CH—CH—(CH 2 ) 0, 1, 2, 3, 4 —CH 3 , —C(O)-optionally substituted phenyl, —C(O)-disubstituted phenyl, —C(O)-p-substituted phenyl, —C(O)-o-substituted phenyl, —CH(CH 3 )—(CH 2 ) 1, 2, 3, 4 —C(═CH 2 )—CH(CH 3 ) 2 , —CH(CH 3 )—(CH 2 ) 1, 2, 3, 4 —CH(CH 3 ) 2 , —C(CH 3 )═N—(CH 2 ) 1, 2, 3, 4 —CH 2 OH, —C(O)—(CH 2 ) 0, 1, 2, 3, 4, 5, 6 —O—C(O)—(CH 2 ) 1, 2, 3, 4, 5, 6 —C(O)—O—C1-C4 optionally substituted alkyl, —C(O)—(CH 2 ) 0, 1, 2, 3, 4, 5, 6 —O—C(O)—(CH 2 ) 1, 2, 3, 4, 5, 6 —C(O)—OR PR , —C≡C-cyclopropyl, —CH═CH-cyclopropyl, —C≡C—C(═CH 2 )—CH 3 , —C≡C—C(═CH 2 )—F, —C≡C—C(═CH 2 )—Cl, —C≡C—C(═CH 2 )—Br, —C≡C—C(═CH 2 )—F, —C≡C—C(═CH 2 )—Cl, —C≡C—C(═CH 2 )—Br, —O—C(O)—CF 3 , —O—C(O)-cyclopropyl, —O—C(O)-cyclobutyl, —O—C(O)—CH 2 —O—C(O)—CH═CH—COOR PR , —O—C(O)—CH(C 2 H 5 )(C 4 H 9 ), —O—C(O)—CH(C 2 H 5 ) 2 , —O—C(O)—CH(C 4 H 9 ) 2 , —O—C(O)—(CH 2 ) 1, 2, 3, 4, 5, 6 —CH 3 , ═CH—O—(CH 2 ) 1, 2, 3, 4, 5, 6 —CH 3 , —CH═CH 2 , —CH(OH)—(CH 2 ) 0, 1, 2, 3, 4 —H, —C(CH 3 )(OH)—(CH 2 ) 0, 1, 2, 3, 4 —H, —O—(C(O)— (CH 2 ) 0, 1, 2, 3, 4 —CH 3 , —O—(C(O)— (CH 2 ) 0, 1, 2, 3, 4 —CF 3 , —C(O)—CH 2 —O—C(O)—CH 2 CH 2 —C(O)OR PR

C1-C10 optionally substituted alkyl, heterocycle, aryl, phosphoenolpyruvate, D-glucosamine, glucholic acid, glucuronic acid, pantothenic acid, pyruvic acid, glucose, fructose, mannose, sucrose, lactose, fucose, rhamnose, galactose, ribose, (O-1)-D-galactopyranosyl-(1-O-4)-D-glucopyranoside, (O-1)-tetra-O-acetyl-D-glucopyranosyl-(1-O-4)-tri-O-acetyl-D-glucopyranoside, 2′-deoxyribose, 3′-deoxyribose, glycerol, 3-phosphoglycerate, a PEG (PEG 20, PEG 100, PEG 200, PEG 10000), a polyoxyalkylene polymer, glycine, alanine, phenylalanine, threonine, proline, 4-hydroxyproline or an oligonucleotide or analog that comprises about 4 to about 21 monomers, where R PR independently are —H or a protecting group. In some embodiments, one, two or three of R 1 , R 2 and R 4 independently are one of these moieties and other variable groups in the F1C are as otherwise defined herein. In other embodiments, one or two of R 10A , R 10B , R 10C , R 10D , are not —H, and 1, 2, 3 or 4 of (1) R 1 , R 3 and R 4 , (2) R 1 , R 2 and R 4 , (3) R 1 , R 3 , R 4 and R 9 , (4) R 1 , R 3 , R 4 and R 8 , (5) R 1 , R 3 , R 4 and R 9 , (6) R 1 , R 2 , R 3 and R 4 , (7) R 1 , R 2 , R 3 , R 4 and R 7 (8) R 1 , R 2 , R 3 , R 4 and R 8 or (9) R 1 , R 2 , R 3 , R 4 and R 9 , independently are one of these moieties, e.g., any substituent except —H, —CH 2 — or ═CH—, while other variable groups, e.g., R 5 and R 6 , are as otherwise defined herein.

F1C embodiments also include compounds where 1, 2 or more of, e.g., R 1 , R 2 , R 3 , R 4 and R 10 are a lipid moiety such as a fatty acid, a monoacylglyceride, a diacylglyceride, a phospholipid, a glycolipid, a sphingolipid or a glycerophospholipid that is esterified, linked through an ether (—O—) or acyl moiety or otherwise bonded to the F1C. Exemplary fatty acid esters include —C(O)—(CH 2 ) m —H where m is 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 15, 17, 19 or 21 and —C(O)—(CH 2 ) n —CH═CH—(CH 2 ) n —H where each n independently is 1, 2, 3, 4, 5, 6, 7 or 8. Other lipid moieties that can be bonded to the steroid include phosphatidic acid, phosphatidylethanolamine, phosphatidylcholine, phosphatidylserine and phosphatidylglycerol. The lipid moiety may be bonded to the steroid through a hydroxyl or oxygen, phosphate, sulfate or amine at a variable group. Such lipid moieties may be bonded to any of the F1Cs or genera of F1Cs disclosed herein.

Specific F1Cs that can be used in the clinical treatments and other methods described herein include the following groups of compounds.

Group 1. Exemplary embodiments include the formula 1 compounds named according to the compound structure designations given in Tables A and B below. Each compound named in Table B is depicted as a compound having formula B

where R 5 and R 6 are both —CH 3 , there is no double bond at the 1-2-, 4-5-, 5-6 or 16-17 positions, R 7 , R 8 and R 9 are all —CH 2 —, R 10A , R 10B , R 10C , R 10D , R 10E , R 10F , R 10G and R 10H are all —H and R 1 , R 2 , R 3 and R 4 are the substituents designated in Table A. The compounds named according to Tables A and B are referred to as “group 1” compounds.

Compounds named in Table B are named by numbers assigned to R 1 , R 2 , R 3 and R 4 according to the following compound naming convention, R 1 .R 2 .R 3 .R 4 , using the numbered chemical substituents in Table A. Each Table A number specifies a different structure for each of R 1 , R 2 , R 3 and R 4 . When R 1 , R 2 , R 3 or R 4 is a divalent moiety, e.g., ═O, the hydrogen at the corresponding position is absent. Thus, the group 1 compound named 1.2.1.1 is a formula B structure with a β-hydroxyl bonded to carbons at the 3- and 7-positions (the variable groups R 1 and R 2 respectively), an α-bromine bonded to carbon 16 (the variable group R 3 ) and double bonded oxygen (═O) at carbon 17 (the variable group R 4 ), i.e., 1.2.4.1 is 3β,7β-dihydroxy-16α-fluoro-17β-aminoandrostane and has the structure

Similarly, group 1 compound 1.2.7.1 is 3β,7β-dihydroxy-16-oxo-17β-aminoandrostane and compound 1.1.4.1 is 3-hydroxy-16α-fluoro-17β-aminoandrostane. Exemplary compounds include 3β,17β-dihydroxy-5α-androstane, 3β,17β-dihydroxy-7β-methyl-5α-androstane, 3β,17β-dihydroxy-7β-methoxy-5α-androstane, 3β,7β,17β-trihydroxy-5α-androstane, 3β-amino-17β-hydroxy-5α-androstane 3β-amino-7β,17β-dihydroxy-5α-androstane, 3β-hydroxy-17β-amino-5α-androstane, 3β,7β-dihydroxy-17β-amino-5α-androstane and 16α-hydroxy, 16-methylene (═CH 2 ), 16-oxo and 16α-halo analogs of any of these compounds.

Additional exemplary formula B compound groups include the following compound groups disclosed below. Unless otherwise specified, the configurations of all hydrogen atoms and R groups for the following compound groups are as defined for the group 1 compounds of formula B above. As is apparent from the description, each of the compound groups disclose a significant number of unique compounds or generic structures. The compounds or generic structures specifically described in any of the compound groups are thus exemplary only and the remaining compounds or structures in each group are described by Tables A and B as noted in each group.

As used in the description of compounds in the compound groups, the definitive structure of compounds in the various compound groups is specified only by the structure defining portion of the compound group and in Tables A and B, which together definitively name or specifies individual compound or genus structures. The structure defining portion of the compound groups is generally contained in the first sentence the compound groups below. This applies regardless of any name or structure, including chemical names in the exemplary compounds that are named in some of the compound groups. Thus, any name or structure for any compound or compound genus that refers to a compound or genus in a compound group and is given anywhere in the disclosure is intended only to refer to the compound or genus that is definitively specified by the compound groups together with Tables A and B.

Group 2. This group comprises compounds named in Table B having R 1 , R 2 , R 3 and R 4 substituents defined in Table A wherein the R 1 , R 2 , R 3 and R 4 substituents are bonded to the steroid nucleus described for group 1 compounds, except that R 10E is hydrogen in the β-configuration. Exemplary compounds include 3β, 17β-dihydroxy-5β-androstane, 3β, 17β-dihydroxy-7β-methyl-5β-androstane, 3β, 17β-dihydroxy-7β-methoxy-5β-androstane, 3β,7β, 17β-trihydroxy-5β-androstane, 3β-amino-17β-hydroxy-5β-androstane 3β-amino-7β, 17β-dihydroxy-5β-androstane, 3β-hydroxy-17β-amino-5β-androstane, 3β,7β-dihydroxy-17β-amino-5β-androstane and 16α-hydroxy, 16-methylene (═CH 2 ), 16-oxo and 16α-halo analogs of any of these compounds.

Group 3. This group comprises compounds named in Table B having R 1 , R 2 , R 3 and R 4 substituents defined in Table A wherein the R 1 , R 2 , R 3 and R 4 substituents are bonded to the steroid nucleus described for group 1 compounds, except that a double bond at the 5-6 position is present. Exemplary compounds include 3β, 17β-dihydroxyandrost-5-ene (compound 1.1.5.9), 3β, 17β-dihydroxy-7β-methylandrost-5-ene, 3β, 17β-dihydroxy-7β-methoxyandrost-5-ene, 3β,7β, 17β-trihydroxyandrost-5-ene, 3β-amino-17β-hydroxyandrost-5-ene 3β-amino-7β, 17β-dihydroxyandrost-5-ene, 3β-hydroxy-17β-aminoandrost-5-ene (compound 1.1.5.1), 3β,7β-dihydroxy-17β-aminoandrost-5-ene and 16α-hydroxy, 16-methylene, 16-oxo and 16α-halo analogs of any of these compounds.

Group 4. This group comprises compounds named in Table B having R 1 , R 2 , R 3 and R 4 substituents defined in Table A wherein the R 1 , R 2 , R 3 and R 4 substituents are bonded to the steroid nucleus as described for group 1 compounds, except that double bonds at the 1-2- and 5-6 positions are present. Exemplary compounds include 3β, 17β-dihydroxyandrost-1,5-diene, 3β, 17β-dihydroxy-7β-methylandrost-1,5-diene, 3β, 17β-dihydroxy-7β-methoxyandrost-1,5-diene, 3β,7β, 17β-trihydroxyandrost-1,5-diene, 3β-amino-17β-hydroxyandrost-1,5-diene 3β-amino-7β, 17β-dihydroxyandrost-1,5-diene, 3β-hydroxy-17β-aminoandrost-1,5-diene, 3β,7β-dihydroxy-17β-aminoandrost-1,5-diene and 16α-hydroxy, 16-methylene, 16-oxo and 16α-halo analogs of any of these compounds.

Group 5. This group comprises compounds named in Table B having R 1 , R 2 , R 3 and R 4 substituents defined in Table A wherein the R 1 , R 2 , R 3 and R 4 substituents are bonded to the steroid nucleus described for group 1 compounds, except that a double bond at the 1-2 position is present. Exemplary compounds include 3β, 17β-dihydroxyandrost-1-ene, 3β, 17β-dihydroxy-7β-methylandrost-1-ene, 3β, 17β-dihydroxy-7β-methoxyandrost-1-ene, 3β,7β, 17β-trihydroxyandrost-1-ene, 3β-amino-17β-hydroxyandrost-1-ene 3β-amino-7β, 17β-dihydroxyandrost-1-ene, 3β-hydroxy-17β-aminoandrost-1-ene, 3β,7β-dihydroxy-17β-aminoandrost-1-ene and 16α-hydroxy, 16-methylene, 16-oxo and 16α-halo analogs of any of these compounds.

Group 5A. This group comprises compounds named in Table B having R 1 , R 2 , R 3 and R 4 substituents defined in Table A wherein the R 1 , R 2 , R 3 and R 4 substituents are bonded to the steroid nucleus described for group 1 compounds, except that a double bond at the 1-2 position is present and hydrogen at the 5-position is in the β-configuration.

Exemplary compounds include 3β, 17β-dihydroxy-5β-androst-1-ene, 3β, 17β-dihydroxy-7β-methyl-5β-androst-1-ene, 3β, 17β-dihydroxy-7β-methoxy-5β-androst-1-ene, 3β,7β, 17β-trihydroxy-5β-androst-1-ene, 3β-amino-17β-hydroxy-5β-androst-1-ene 3β-amino-7β, 17β-dihydroxy-5β-androst-1-ene, 3β-hydroxy-17β-amino-5β-androst-1-ene, 3β,7β-dihydroxy-17β-amino-5β-androst-1-ene and 16α-hydroxy, 16-methylene, 16-oxo and 16α-halo analogs of any of these compounds.

Group 6. This group comprises compounds named in Table B having R 1 , R 2 , R 3 and R 4 substituents defined in Table A wherein the R 1 , R 2 , R 3 and R 4 substituents are bonded to the steroid nucleus described for group 1 compounds, except that a double bond at the 4-5 position is present. Exemplary compounds include 3β, 17β-dihydroxyandrost-4-ene, 3β, 17β-dihydroxy-7β-methylandrost-4-ene, 3β, 17β-dihydroxy-7β-methoxyandrost-4-ene, 3β,7β, 17β-trihydroxyandrost-4-ene, 3β-amino-17β-hydroxyandrost-4-ene 3β-amino-7β, 17β-dihydroxyandrost-4-ene, 3β-hydroxy-17β-aminoandrost-4-ene, 3β,7β-dihydroxy-17β-aminoandrost-4-ene and 16α-hydroxy, 16-methylene, 16-oxo and 16α-halo analogs of any of these compounds.

Group 7. This group comprises compounds named in Table B having R 1 , R 2 , R 3 and R 4 substituents defined in Table A wherein the R 1 , R 2 , R 3 and R 4 substituents are bonded to the steroid nucleus described for group 1 compounds, except that double bonds at both the 1-2 and 4-5 positions are present. Exemplary compounds include 3β, 17β-dihydroxyandrost-1,4-diene, 3β, 17β-dihydroxy-7β-methylandrost-1,4-diene, 3β, 17β-dihydroxy-7β-methoxyandrost-1,4-diene, 3β,7β, 17β-trihydroxyandrost-1,4-diene, 3β-amino-17β-hydroxyandrost-1,4-diene 3β-amino-7β, 17β-dihydroxyandrost-1,4-diene, 3β-hydroxy-17β-aminoandrost-1,4-diene, 3β,7β-dihydroxy-17β-aminoandrost-1,4-diene and 16α-hydroxy, 16-methylene, 16-oxo and 16α-halo analogs of any of these compounds.

Group 8. This group comprises compounds named in Table B having R 1 , R 2 , R 3 and R 4 substituents defined in Table A wherein the R 1 , R 2 , R 3 and R 4 substituents are bonded to the steroid nucleus described for group 1 compounds, except that a double bond at the 16-17 position is present. For this group and other compound groups that contain a 16-17 double bond, the R 3 and R 4 moieties will only be single bonded. Moieties such as ═O are thus not included as R 3 or R 4 substituents in the compound group, since this would give rise to a pentavalent carbon at the 16- or 17-position. Group 8 compound 1.2.7.1 does not represent any compound since a 16-17 double bond and an ═O at 16 can not both be present at the same time. Exemplary compounds include 3β, 17-dihydroxy-5α-androst-16-ene, 3β, 17-dihydroxy-7β-methyl-5α-androst-16-ene, 3β, 17-dihydroxy-7β-methoxy-5α-androst-16-ene, 3β,7β, 17-trihydroxy-5α-androst-16-ene, 3β-amino-17-hydroxy-5α-androst-16-ene 3β-amino-7β, 17-dihydroxy-5α-androst-16-ene, 3β-hydroxy-17-amino-5α-androst-16-ene, 3β,7β-dihydroxy-17-amino-5α-androst-16-ene and 16-hydroxy, and 16-halo analogs of any of these compounds. Since a double bond is present at the 16-17 position, there are no 16-oxo or 16-methylene compounds in this group, or in other groups, e.g., groups 8A, 9 or 10 below, where a double bond is present at the 16-17 position. Thus, group 8 compound 1.1.7.1 and 1.1.10.1 are not included in group 8.

Group 8A. This group comprises compounds named in Table B having R 1 , R 2 , R 3 and R 4 substituents defined in Table A wherein the R 1 , R 2 , R 3 and R 4 substituents are bonded to the steroid nucleus described for group 1 compounds, except that a double bond at the 16-17 position is present and hydrogen at the 5-position is in the β-configuration. Exemplary compounds include 3β, 17-dihydroxy-5β-androst-16-ene, 3β, 17-dihydroxy-7β-methyl-5β-androst-16-ene, 3β, 17-dihydroxy-7β-methoxy-5β-androst-16-ene, 3β,7β, 17-trihydroxy-5β-androst-16-ene, 3β-amino-17-hydroxy-5β-androst-16-ene 3β-amino-7β, 17-dihydroxy-5β-androst-16-ene, 3β-hydroxy-17-amino-5β-androst-16-ene, 3β,7β-dihydroxy-17-amino-5β-androst-16-ene and 16-hydroxy and 16-halo analogs of any of these compounds.

Group 9. This group comprises compounds named in Table B having R 1 , R 2 , R 3 and R 4 substituents defined in Table A wherein the R 1 , R 2 , R 3 and R 4 substituents are bonded to the steroid nucleus described for group 1 compounds, except that double bonds at the 16-17 and 5-6 positions are present. Exemplary compounds include 3β, 17-dihydroxyandrost-5,16-diene, 3β, 17-dihydroxy-7β-methylandrost-5,16-diene, 3β, 17-dihydroxy-7β-methoxyandrost-5,16-diene, 3β,7β, 17-trihydroxyandrost-5,16-diene, 3β-amino-17-hydroxyandrost-5,16-diene 3β-amino-7β, 17-dihydroxyandrost-5,16-diene, 3β-hydroxy-17-aminoandrost-5,16-diene, 3β,7β-dihydroxy-17-aminoandrost-5,16-diene and 16-hydroxy and 16-halo analogs of any of these compounds.

Group 10. This group comprises compounds named in Table B having R 1 , R 2 , R 3 and R 4 substituents defined in Table A wherein the R 1 , R 2 , R 3 and R 4 substituents are bonded to the steroid nucleus described for group 1 compounds, except that double bonds at the 16-17 and 1-2 positions are present. Exemplary compounds include 3β, 17-dihydroxy-5α-androst-1,16-ene, 3β, 17-dihydroxy-7β-methyl-5α-androst-1,16-ene, 3β, 17-dihydroxy-7β-methoxy-5α-androst-1,16-ene, 3β,7β, 17-trihydroxy-5α-androst-1,16-ene, 3β-amino-17-hydroxy-5α-androst-1,16-ene 3β-amino-7β, 17-dihydroxy-5α-androst-1,16-ene, 3β-hydroxy-17-amino-5α-androst-1,16-ene, 3β,7β-dihydroxy-17-amino-5α-androst-1,16-ene and 16-hydroxy and 16-halo analogs of any of these compounds.

Group 10A. This group comprises compounds named in Table B having R 1 , R 2 , R 3 and R 4 substituents defined in Table A wherein the R 1 , R 2 , R 3 and R 4 substituents are bonded to the steroid nucleus described for group 1 compounds, except that a double bond at the 16-17 and 1-2 positions are present and hydrogen at the 5-position is in the β-configuration. Exemplary compounds include 3β, 17-dihydroxy-5β-androst-1,16-ene, 3β, 17-dihydroxy-7β-methyl-5β-androst-1,16-ene, 3β, 17-dihydroxy-7β-methoxy-5β-androst-1,16-ene, 3β,7β, 17-trihydroxy-5β-androst-1,16-ene, 3β-amino-17-hydroxy-5β-androst-1,16-ene 3β-amino-7β, 17-dihydroxy-5β-androst-1,16-ene, 3β-hydroxy-17-amino-5β-androst-1,16-ene, 3β,7β-dihydroxy-17-amino-5β-androst-1,16-ene and 16-hydroxy and 16-halo analogs of any of these compounds.

Group 11. This group comprises compounds named in Table B having R 1 , R 2 , R 3 and R 4 substituents defined in Table A wherein the R 1 , R 2 , R 3 and R 4 substituents are bonded to the steroid nucleus described for group 1 compounds, except that double bonds at the 16-17 and 4-5 positions are present. Exemplary compounds include 3β, 17-dihydroxyandrost-4,16-diene, 3β, 17-dihydroxy-7β-methylandrost-4,16-diene, 3β, 17-dihydroxy-7β-methoxyandrost-4,16-diene, 3β,7β, 17-trihydroxyandrost-4,16-diene, 3β-amino-17-hydroxyandrost-4,16-diene 3β-amino-7β, 17-dihydroxyandrost-4,16-diene, 3β-hydroxy-17-aminoandrost-4,16-diene, 3β,7β-dihydroxy-17-aminoandrost-4,16-diene and 16-hydroxy and 16-halo analogs of any of these compounds.

Group 12. This group comprises compounds named in Table B having R 1 , R 2 , R 3 and R 4 substituents defined in Table A wherein the R 1 , R 2 , R 3 and R 4 substituents are bonded to the steroid nucleus described for group 1 compounds, except that double bonds at the 1-2, 16-17 and 4-5 positions are present. Exemplary compounds include 3β, 17-dihydroxyandrost-1,4,16-triene, 3β, 17-dihydroxy-7β-methylandrost-1,4,16-triene, 3β, 17-dihydroxy-7β-methoxyandrost-1,4,16-triene, 3β,7β, 17-trihydroxyandrost-1,4,16-triene, 3β-amino-17-hydroxyandrost-1,4,16-triene 3β-amino-7β, 17-dihydroxyandrost-1,4,16-triene, 3β-hydroxy-17-aminoandrost-1,4,16-triene, 3β,7β-dihydroxy-17-aminoandrost-1,4,16-triene and 16-hydroxy, and 16-halo analogs of any of these compounds.

Group 13. This group comprises compounds named in Table B having R 1 , R 2 , R 3 and R 4 substituents defined in Table A wherein the R 1 , R 2 , R 3 and R 4 substituents are bonded to the steroid nucleus described for group 1 compounds, except that double bonds at the 1-2, 16-17 and 5-6 positions are present. Exemplary compounds include 3β, 17-dihydroxyandrost-1,5,16-triene, 3β, 17-dihydroxy-7β-methylandrost-1,5,16-triene, 3β, 17-dihydroxy-7β-methoxyandrost-1,5,16-triene, 3β,7β, 17-trihydroxyandrost-1,5,16-triene, 3β-amino-17-hydroxyandrost-1,5,16-triene 3β-amino-7β, 17-dihydroxyandrost-1,5,16-triene, 3β-hydroxy-17-aminoandrost-1,5,16-triene, 3β,7β-dihydroxy-17-aminoandrost-1,5,16-triene and 16-hydroxy, and 16-halo analogs of any of these compounds.

Group 14. This group contains compounds from groups 1-13 above wherein, for single bonded R 1 , R 2 , R 3 and R 4 moieties, R 1 , R 2 , R 3 and R 4 respectively are in the α,β,α,β, β,β,α,α, β,α,α,β, α,α,α,β, β,β,β,β, β,β,β,α, α,β,β,β, β,α,α,α, β,α,β,β, α,α,α,α, β,α,β,α, α,β,β,α, α,α,β,α, α,β,α,α or α,α,β,β configurations. Thus, R 1 , R 2 , R 3 and R 4 respectively may be, for example, in the α,β,α,β configurations or in the β,β,α,α configurations or in the β,β,β,β configurations respectively or in the α,β,β,β configurations respectively or in the α,β,β,α configurations respectively.

Thus, when R 1 , R 2 , R 3 and R 4 respectively are in the α,β,α,β configurations, group 14 compound 1.2.7.1 from group 3 (also referred to as group 14-3 compound 1.2.7.1) is 3α,7β-dihydroxy-16-oxo-17β-aminoandrost-5-ene and compound 1.1.4.1 from group 3 (also referred to as group 14-3 compound 1.1.4.1) is 3α-hydroxy-16α-fluoro-17β-aminoandrost-5-ene. When R 1 , R 2 , R 3 and R 4 respectively are in the α,β,α,β configurations, group 14 compound 1.2.7.1 from group 1 (also referred to as group 14-1 compound 1.2.7.1) is 3α,7β-dihydroxy-16-oxo-17β-aminoandrostane and group 14-1 compound 1.1.4.1 is 3α-hydroxy-16α-fluoro-17β-aminoandrostane. Similarly, when R 1 , R 2 , R 3 and R 4 respectively are in the α,β,α,β configurations, group 14-6 compound 1.2.7.1 is 3α,7β-dihydroxy-16-oxo-17β-aminoandrost-4-ene and group 14-6 compound 1.1.4.1 is 3α-hydroxy-16α-fluoro-17β-aminoandrost-4-ene.

Similarly, when R 1 , R 2 , R 3 and R 4 respectively are in the α,β,β,α configurations, group 14-3 compound 1.2.6.1 is 3α,7β,16β-trihydroxy-17α-aminoandrost-5-ene and group 14-3 compound 1.1.4.1 is 3α-hydroxy-16β-fluoro-17β-aminoandrost-5-ene. When R 1 , R 2 , R 3 and R 4 respectively are in the β,β,α,α configurations, group 14-3 compound 1.2.6.1 is 3β,7β,16α-trihydroxy-17α-aminoandrost-5-ene and group 14-3 compound 1.1.4.1 is 3β-hydroxy-16α-fluoro-17α-aminoandrost-5-ene. When R 1 , R 2 , R 3 and R 4 respectively are in the α,β,β,α configurations, group 14-4 compound 1.2.6.1 is 3α,7β,16β-trihydroxy-17α-aminoandrost-1,5-diene and group 14-4 compound 1.1.4.1 is 3α-hydroxy-16β-fluoro-17β-aminoandrost-1,5-diene. When R 1 , R 2 , R 3 and R 4 respectively are in the β,β,α,α configurations, group 14-4 compound 1.2.6.1 is 3β,7β,16α-trihydroxy-17α-aminoandrost-1,5-diene and group 14-4 compound 1.1.4.1 is 3β-hydroxy-16α-fluoro-17α-aminoandrost-1,5-diene. When R 1 , R 2 , R 3 and R 4 respectively are in the α,β,β,α configurations, group 14-2 compound 1.2.6.1 is 3α,7β,16β-trihydroxy-17α-amino-5β-androstane and group 14-2 compound 1.1.4.1 is 3α-hydroxy-16β-fluoro-17α-amino-5β-androstane. When R 1 , R 2 , R 3 and R 4 respectively are in the β,β,α,α configurations, group 14-2 compound 1.2.6.1 is 3β,7β,16α-trihydroxy-17α-amino-5β-androstane and group 14-2 compound 1.1.4.1 is 3β-hydroxy-16α-fluoro-17α-amino-5β-androstane. When R 1 , R 2 , R 3 and R 4 respectively are in the α,β,α,β configurations, group 14-2 compound 1.2.6.1 is 3α,7β,16α-trihydroxy-17β-amino-5β-androstane and group 14-2 compound 1.1.4.1 is 3α-hydroxy-16β-fluoro-17β-amino-5β-androstane. When R 1 , R 2 , R 3 and R 4 respectively are in the β,β,β,α configurations, group 14-2 compound 1.2.6.1 is 3β,7β,16β-trihydroxy-17α-amino-5β-androstane and group 14-2 compound 1.1.4.1 is 3β-hydroxy-16β-fluoro-17α-amino-5β-androstane. Compounds in other groups, e.g., groups 14-5, 14-5A, 14-6, 14-7, 14-8, 14-8A, 14-9, 14-10, 14-10A, 14-11, 14-12 or 14-13, where R 1 , R 2 , R 3 and R 4 respectively are in the listed configurations, e.g., α,β,α,β, β,β,β,α, β,β,α,α or β,β,β,β, are named or described in the same manner.

Group 15. This group contains compounds in groups 1-14 above wherein R 10F , R 10G and R 10H respectively are in the β,α,β, β,β,α, α,β,β, β,β,β, α,α,α, α,β,α or α,α,β configurations. Thus, when R 10F , R 10G and R 10H respectively can be in the β,α,β configurations. Group 15 compounds include groups 15-1 through 15-14-13. Groups 15-1, 15-2, 15-3, 15-4, 15-5, 15-5A, 15-6, 15-7, 15-8, 15-8A, 15-9, 15-10, 15-10A, 15-11, 15-12 and 15-13 are compounds as described in groups 1 through 13 respectively, but where R 10F , R 10G and R 10H respectively are in the listed configurations respectively, e.g., the β,α,β or β,β,α configurations, instead of being in the β,α,α configurations shown in groups 1 through 13. Similarly, compound groups 15-14-1, 15-14-2, 15-14-3, 15-14-4, 15-14-5, 15-14-5A, 15-14-6, 15-14-7, 15-14-8, 15-14-8A, 15-14-9, 15-14-10, 15-14-10A, 15-14-11, 15-14-12 and 15-14-11 are compounds as described in group 14 where (1) where R 10F , R 10G and R 10H respectively are in the listed configurations respectively, e.g., the β,α,β or β,β,α configurations, and (2) R 1 , R 2 , R 3 and R 4 respectively are in the listed configurations, e.g., the α,β,α,β, β,α,α,β, β,β,β,α, β,β,α,α or β,β,β,β configurations, as described in group 14.

Group 16. This group contains compounds in groups 1-15 above wherein 1, 2, 3 or 4 of R 10A , R 10B , R 10C and R 10D are not —H and are an independently chosen moiety as defined herein, e.g., optionally substituted alkyl such as methyl, ethyl, fluoromethyl or hydroxymethyl, —F, —Cl, —Br, —I, —SR PR , —OR PR , —N(R PR ) 2 , —OH, ═O, —SH, ═S, —NH 2 , —NHCH 3 , —N(CH 3 ) 2 , ═NOH, ═NCH 3 , ether, thioether, ester, carbamate, amide, optionally substituted heterocycle, optionally substituted monosaccharide or optionally substituted oligosaccharide, wherein each R 10A , R 10B , R 10C and R 10D is independently in the α-configuration or the β-configuration and R PR independently are —H or a protecting group. Thus, when R 10C and R 10D are both not —H, they can be in the β,β, β,α, α,β or α,α configurations respectively, when they are linked by a single bond. Similarly, when R 10B and R 10D are both not —H, they can be in the β,β, β,α, α,β or α,α configurations respectively, or, when R 10B is not —H and R 10A , R 10C and R 10D are all —H, R 10B can be in the α-configuration or the β-configuration.

This group includes groups 16-1 through 16-15-14-13. These compound groups include (1) 16-1, 16-2, 16-3, 16-4, 16-5, 16-5A, 16-6, 16-7, 16-8, 16-8A, 16-9, 16-10, 16-10A, 16-11, 16-12 and 16-13, which are compounds in groups 1 through 13 where one or more of R 10A , R 10B , R 10C and R 10D are substituted, (2) 16-14-1, 16-14-2, 16-14-3, 16-14-4, 16-14-5, 16-14-5A, 16-14-6, 16-14-7, 16-14-8, 16-14-8A, 16-14-9, 16-14-10, 16-14-10A, 16-14-11, 16-14-12 and 16-14-13, which are the group 14 compounds where one or more of R 10A , R 10B , R 10C and R 10D are substituted and where R 1 , R 2 , R 3 and R 4 are in the configurations specified in group 14, e.g., α,β,α,β, β,β,β,β, α,β,β,α or β,β,α,α, (3) 16-15-1, 16-15-2, 16-15-3, 16-15-4, 16-15-5, 16-15-5A, 16-15-6, 16-15-7, 16-15-8, 16-15-8A, 16-15-9, 16-15-10, 16-15-10A, 16-15-11, 16-15-12 and 16-15-13, which are the group 16 compounds and (4) groups 16-15-14-1, 16-15-14-2, 16-15-14-3, 16-15-14-4, 16-15-14-5, 16-15-14-5A, 16-15-14-6, 16-15-14-7, 16-15-14-8, 16-15-14-8A, 16-15-14-9, 16-15-14-10, 16-15-14-10A, 16-15-14-11, 16-15-14-12 and 16-15-14-13, which are group 14 compounds in group 15.

Group 17. This group contains compounds in groups 1-16 above wherein (1) one or both of R 5 and R 6 are not —CH 3 and they independently are a moiety as defined herein, and (2) R 5 and R 6 are in the β,β, β,α, α,β or α,α configurations respectively. Thus, R 5 and R 6 independently can be —H, —CH 3 , —C 2 H 5 , —C 3 H 7 , optionally substituted alkyl, —OH, —F, —Cl, —Br, —I or another single bonded moiety as defined herein in the β,β, β,α, α,β or α,α configurations. Thus, for example, R 5 can be —CH 3 , —CH 2 OH, —CHO or —C 2 H 5 and R 6 can be —H, where both are in the β-configuration or R 5 can be optionally substituted alkyl and R 6 can be —H, where both are in, e.g., the β,α or α,β configurations respectively instead of both being in the β-configuration as in groups 1 through 16.

This group includes groups 17-1 through 17-16-15-14-13. These compound groups include (1) 17-1, 17-2, 17-3, 17-4, 17-5, 17-5A, 17-6, 17-7, 17-8, 17-8A, 17-9, 17-10, 17-10A, 17-11, 17-12 and 17-13, which are compounds in groups 1 through 13 where one or both of R 5 and R 6 are not —CH 3 , e.g., R 5 is —H, —C 2 H 5 , —CH 2 OH and R 6 is —H, —CH 3 , —CH 2 OH, —CH 2 F or —C 2 H 5 , and they independently are a moiety as defined herein, and where R 5 and R 6 are in the β,β, β,α, α,β or α,α configurations respectively, (2) 17-14-1, 17-14-2, 17-14-3, 17-14-4, 17-14-5, 17-14-5A, 17-14-6, 17-14-7, 17-14-8, 17-14-8A, 17-14-9, 17-14-10, 17-14-10A, 17-14-11, 17-14-12 and 17-14-13, which are compounds in group 14 where one or both of R 5 and R 6 are not —CH 3 and are optionally in other configurations than is shown for group 1 and where R 1 , R 2 , R 3 and R 4 are in the configurations described in group 14, e.g., α,β,α,β, β,β,β,β, β,β,β,α or β,β,α,α respectively, (3) 17-15-1, 17-15-2, 17-15-3, 17-15-4, 17-15-5, 17-15-5A, 17-15-6, 17-15-7, 17-15-8, 17-15-8A, 17-15-9, 17-15-10, 17-15-10A, 17-15-11, 17-15-12 and 17-15-13, which are compounds in group 15 where one or both of R 5 and R 6 are not —CH 3 and are optionally in other configurations than is shown for group 1, (4) 17-16-1, 17-16-2, 17-16-3, 17-16-4, 17-16-5, 17-16-5A, 17-16-6, 17-16-7, 17-16-8, 17-16-8A, 17-16-9, 17-16-10, 17-16-10A, 17-16-11, 17-16-12 and 17-16-13, which are compounds in group 16 where one or both of R 5 and R 6 are not —CH 3 and are optionally in other configurations than is shown for group 1, (5) 17-16-14-1, 17-16-14-2, 17-16-14-3, 17-16-14-4, 17-16-14-5, 17-16-14-5A, 17-16-14-6, 17-16-14-7, 17-16-14-8, 17-16-14-8A, 17-16-14-9, 17-16-14-10, 17-16-14-10A, 17-16-14-11, 17-16-14-12 and 17-16-14-13, which are the group 14 compounds in group 16 where one or more of R 10A , R 10B , R 10C and R 10D are substituted and where R 1 , R 2 , R 3 and R 4 are in the configurations specified in group 14, e.g., α,β,α,β, β,β,β,β, α,β,β,α or β,β,α,α respectively, (6) 17-15-14-1, 17-15-14-2, 17-15-14-3, 17-15-14-4, 17-15-14-5, 17-15-14-5A, 17-15-14-6, 17-15-14-7, 17-15-14-8, 17-15-14-8A, 17-15-14-9, 17-15-14-10, 17-15-14-10A, 17-15-14-11, 17-15-14-12 and 17-15-14-13, which are the group 14 compounds in group 15 where one or more of R 10A , R 10B , R 10C and R 10D are substituted and where R 1 , R 2 , R 3 and R 4 are in the configurations specified in group 14, e.g., α,β,α,β, β,β,β,β, α,β,β,α or β,β,α,α respectively, (7) 17-16-15-1, 17-16-15-2, 17-16-15-3, 17-16-15-4, 17-16-15-5, 17-16-15-5A, 17-16-15-6, 17-16-15-7, 17-16-15-8, 17-16-15-8A, 17-16-15-9, 17-16-15-10, 17-16-15-10A, 17-16-15-11, 17-16-15-12 and 17-16-15-13, which are the group 15 compounds in group 16, and (8) groups 17-16-15-14-1, 17-16-15-14-2, 17-16-15-14-3, 17-16-15-14-4, 17-16-15-14-5, 17-16-15-14-5A, 17-16-15-14-6, 17-16-15-14-7, 17-16-15-14-8, 17-16-15-14-8A, 17-16-15-14-9, 17-16-15-14-10, 17-16-15-14-10A, 17-16-15-14-11, 17-16-15-14-12 and 17-16-15-14-13, which are the group 14 compounds in the 16-15 groups.

When R 5 is —CH 3 in the β-configuration, R 6 is —H in the β-configuration exemplary compounds include group 17-1 compound 1.1.4.1, 3β-hydroxy-16α-fluoro-17α-amino-19-nor-5α-androstane, group 17-1 compound 1.1.5.1, 3β-hydroxy-17α-amino-19-nor-5α-androstane, group 17-1 compound 1.1.6.1, 3β,16α-dihydroxy-17α-amino-19-nor-5α-androstane. Other compounds where R 5 is —CH 3 in the β-configuration and R 6 is —H in the β-configuration include (1) group 17-2 compounds 1.1.4.1, 1.1.5.1 and 1.1.6.1, i.e., 3β-hydroxy-16α-fluoro-17β-amino-19-nor-5β-androstane, 3β-hydroxy-17β-amino-19-nor-5β-androstane, and 3β,16α-dihydroxy-17β-amino-19-nor-5β-androstane, (2) group 17-3 compounds 1.1.4.1, 1.1.5.1 and 1.1.6.1, i.e., 3β-hydroxy-16α-fluoro-17β-amino-19-norandrost-5-ene, 3β-hydroxy-17β-amino-19-norandrost-5-ene, and 3β,16α-dihydroxy-17β-amino-19-norandrost-5-ene, (3) group 17-4 compounds 1.1.4.1, 1.1.5.1 and 1.1.6.1, i.e., 3β-hydroxy-16α-fluoro-17β-amino-19-norandrost-1,5-diene, 3β-hydroxy-17β-amino-19-norandrost-1,5-diene, and 3β,16α-dihydroxy-17β-amino-19-norandrost-1,5-diene, (4) group 17-6 compounds 1.1.4.1, 1.1.5.1 and 1.1.6.1, i.e., 3β-hydroxy-16α-fluoro-17β-amino-19-norandrost-4-ene, 3β-hydroxy-17α-amino-19-norandrost-4-ene, and 3β,16α-dihydroxy-17β-amino-19-norandrost-4-ene, (5) group 17-9 compounds 1.1.4.1, 1.1.5.1 and 1.1.6.1, i.e., 3β-hydroxy-16-fluoro-17-amino-19-norandrost-5,16-diene, 3β-hydroxy-17-amino-19-norandrost-5,16-diene, and 3β,16-dihydroxy-17-amino-19-norandrost-5,16-diene, (6) group 17-14-1 compounds 1.1.4.1, 1.1.5.1 and 1.1.6.1, where R 1 is in the α-configuration, i.e., 3α-hydroxy-16α-fluoro-17β-amino-19-nor-5α-androstane, 3α-hydroxy-17β-amino-19-nor-5α-androstane, and 3α,16α-dihydroxy-17β-amino-19-nor-5β-androstane, (7) group 17-14-2 compounds 1.1.4.1, 1.1.5.1 and 1.1.6.1, where R 1 is in the α-configuration, i.e., 3α-hydroxy-16α-fluoro-17β-amino-19-nor-5β-androstane, 3α-hydroxy-17β-amino-19-nor-5β-androstane, and 3α,16α-dihydroxy-17β-amino-19-nor-5β-androstane, (8) group 17-14-3 compounds 1.1.4.1, 1.1.5.1 and 1.1.6.1, where R 1 is in the α-configuration, i.e., 3α-hydroxy-16α-fluoro-17β-amino-19-norandrost-5-ene, 3α-hydroxy-17β-amino-19-norandrost-5-ene, and 3α,16α-dihydroxy-17β-amino-19-norandrost-5-ene, (9) group 17-14-4 compounds 1.1.4.1, 1.1.5.1 and 1.1.6.1, where R 1 is in the α-configuration, i.e., 3α-hydroxy-16α-fluoro-17β-amino-19-norandrost-1,5-diene, 3α-hydroxy-17β-amino-19-norandrost-1,5-diene, and 3α,16α-dihydroxy-17β-amino-19-norandrost-1,5-diene, (10) group 17-14-6 compounds 1.1.4.1, 1.1.5.1 and 1.1.6.1, where R 1 is in the α-configuration, i.e., 3α-hydroxy-16α-fluoro-17β-amino-19-norandrost-4-ene, 3α-hydroxy-17β-amino-19-norandrost-4-ene, and 3α,16α-dihydroxy-17β-amino-19-norandrost-4-ene, and (11) group 17-14-9 compounds 1.1.4.1, 1.1.5.1 and 1.1.6.1, i.e., 3α-hydroxy-16-fluoro-17-amino-19-norandrost-5,16-diene, 3α-hydroxy-17-amino-19-norandrost-5,16-diene, and 3α,16-dihydroxy-17-amino-19-norandrost-5,16-diene. Other exemplary analogs of these compounds include those where (1) R 5 is, e.g., —CH 2 OH, —C 2 H 5 , —CH 2 OCH 3 or another moiety described herein for R 5 or R 6 and/or (2) similar analogs in other groups such as 17-5A, 17-14-5A, 17-7, 17-14-7, 17-11, 17-14-11, 17-13, 17-15-1, 17-15-2, 17-15-3, 17-15-4, 17-15-5, 17-15-5A, 17-15-6, 17-15-14-1, 17-15-14-2, 17-15-14-3, 17-15-14-4, 17-15-14-5, 17-15-14-5A, 17-16-1, 17-16-2, 17-16-3, 17-16-4, 17-16-5, 17-16-5A, 17-16-6, 17-16-14-1, 17-16-14-2, 17-16-14-3, 17-16-14-4, 17-16-14-5, 17-16-14-5A, and 17-16-14-6 where, for compounds in group 14 in group 17 such as 17-14-5A, R 1 , R 2 , R 3 and R 4 can be in, e.g., the β,β,α,β, α,β,α,β, β,β,α,α, β,α,α,β, α,β,β,β, α,β,α,α or β,β,β,β configurations respectively, as described in group 14.

Group 18. This group contains compounds in groups 1-17 above wherein R 9 is not —CH 2 — and is another R 9 moiety defined herein, e.g., —O—, —NH—, —S—, —CH 2 —CH 2 —, —CHR 10 — or —C(R 10 ) 2 — where each R 10 is an independently chosen moiety described herein, where one or both R 10 are in the β-configuration and the other R 10 is in the α-configuration. Exemplary R 9 include —O—, —C(halogen) 2 - such as —CF 2 —, —CH(α-optionally substituted alkyl), —CH(β-optionally substituted alkyl), —CH(α-OH), —CH(β-OH) or —C(optionally substituted alkyl) 2 - such as —C(CH 3 ) 2 — or —C(C 2 H 5 )(CH 3 )—. Each optionally substituted alkyl group can contain 1, 2, 3, 4, 5, 6, 7, 8 or more carbon atoms as defined previously. For groups that contain a double bond at the 1-2 position such as groups 5 and 7, R 9 can be —N═, but R 9 will not be —O— or —S— due to improper bonding, i.e., —O═ and —S═ are not present in the steroid ring. Exemplary compounds include those exemplified in the groups above, e.g., in groups 1, 14 or 17, where R 9 is, e.g., —O—, —NH—, —N═, —CH(α-F)—, —CH(β-F)—, —CF 2 —, —CH(α-optionally substituted alkyl)- or —CH(β-optionally substituted alkyl)-. These compounds include compounds in group 18-1 through 18-17-16-15-14-13, which collectively are group 18 compounds. These include groups 18-1, 18-2, 18-3, 18-4, 18-5, 18-5A, 18-6, 18-7, 18-8, 18-8A, 18-9, 18-10, 18-10A, 18-11, 18-12, 18-13, which are compounds in groups 1 through 13 where R 9 is not —CH 2 —. Group 18 compounds also include groups 18-14-1, 18-14-2, 18-14-3, 18-14-4, 18-14-5, 18-14-5A, 18-14-6, 18-14-7, 18-14-8, 18-14-8A, 18-14-9, 18-14-10, 18-14-10A, 18-14-11, 18-14-12 and 18-14-13, which are group 14 compounds in groups 14-1 through 14-13 where R 9 is not —CH 2 —.

Other group 18 compounds include (1) groups 18-15-1, 18-15-2, 18-15-3, 18-15-4, 18-15-5, 18-15-5A, 18-15-6, 18-15-7, 18-15-8, 18-15-8A, 18-15-9, 18-15-10, 18-15-10A, 18-15-11, 18-15-12 and 18-15-13, which are group 15 compounds in groups 15-1 through 15-13 where R 9 is not —CH 2 —, (2) groups 18-16-1, 18-16-2, 18-16-3, 18-16-4, 18-16-5, 18-16-5A, 18-16-6, 18-16-7, 18-16-8, 18-16-8A, 18-16-9, 18-16-10, 18-16-10A, 18-16-11, 18-16-12 and 18-16-13, which are group 16 compounds in groups 16-1 through 16-13 where R 9 is not —CH 2 —, (3) groups 18-17-1, 18-17-2, 18-17-3, 18-17-4, 18-17-5, 18-17-5A, 18-17-6, 18-17-7, 18-17-8, 18-17-8A, 18-17-9, 18-17-10, 18-17-10A, 18-17-11, 18-17-12 and 18-17-13, which are group 17 compounds in groups 17-1 through 17-13 where R 9 is not —CH 2 —, (4) groups 18-15-14-1, 18-15-14-2, 18-15-14-3, 18-15-14-4, 18-15-14-5, 18-15-14-5A, 18-15-14-6, 18-15-14-7, 18-15-14-8, 18-15-14-8A, 18-15-14-9, 18-15-14-10, 18-15-14-10A, 18-15-14-11, 18-15-14-12 and 18-15-14-13, which are group 15 compounds in groups 15-14-1 through 15-14-13 where R 9 is not —CH 2 —, (5) groups 18-16-14-1, 18-16-14-2, 18-16-14-3, 18-16-14-4, 18-16-14-5, 18-16-14-5A, 18-16-14-6, 18-16-14-7, 18-16-14-8, 18-16-14-8A, 18-16-14-9, 18-16-14-10, 18-16-14-10A, 18-16-14-11, 18-16-14-12 and 18-16-14-13, which are group 16 compounds in groups 16-14-1 through 16-14-13 where R 9 is not —CH 2 —, (6) groups 18-17-14-1, 18-17-14-2, 18-17-14-3, 18-17-14-4, 18-17-14-5, 18-17-14-5A, 18-17-14-6, 18-17-14-7, 18-17-14-8, 18-17-14-8A, 18-17-14-9, 18-17-14-10, 18-17-14-10A, 18-17-14-11, 18-17-14-12, 18-17-14-13, which are group 17 compounds in groups 17-14-1 through 17-14-13 where R 9 is not —CH 2 —, (7) groups 18-16-15-1, 18-16-15-2, 18-16-15-3, 18-16-15-4, 18-16-15-5, 18-16-15-5A, 18-16-15-6, 18-16-15-7, 18-16-15-8, 18-16-15-8A, 18-16-15-9, 18-16-15-10, 18-16-15-10A, 18-16-15-11, 18-16-15-12, 18-16-15-13, which are group 16 compounds in groups 16-15-1 through 16-15-13 where R 9 is not —CH 2 —, (8) groups 18-17-15-1, 18-17-15-2, 18-17-15-3, 18-17-15-4, 18-17-15-5, 18-17-15-5A, 18-17-15-6, 18-17-15-7, 18-17-15-8, 18-17-15-8A, 18-17-15-9, 18-17-15-10, 18-17-15-10A, 18-17-15-11, 18-17-15-12, 18-17-15-13, which are group 17 compounds in groups 17-15-1 through 17-15-13 where R 9 is not —CH 2 —, (9) groups 18-17-16-1, 18-17-16-2, 18-17-16-3, 18-17-16-4, 18-17-16-5, 18-17-16-5A, 18-17-16-6, 18-17-16-7, 18-17-16-8, 18-17-16-8A, 18-17-16-9, 18-17-16-10, 18-17-16-10A, 18-17-16-11, 18-17-16-12, 18-17-16-13, which are group 17 compounds in groups 17-16-1 through 17-16-13 where R 9 is not —CH 2 —, (10) groups 18-16-15-14-1, 18-16-15-14-2, 18-16-15-14-3, 18-16-15-14-4, 18-16-15-14-5, 18-16-15-14-5A, 18-16-15-14-6, 18-16-15-14-7, 18-16-15-14-8, 18-16-15-14-8A, 18-16-15-14-9, 18-16-15-14-10, 18-16-15-14-10A, 18-16-15-14-11, 18-16-15-14-12, 18-16-15-14-13, which are group 16 compounds in groups 16-15-14-1 through 16-15-14-13 where R 9 is not —CH 2 —, (11) groups 18-17-15-14-1, 18-17-15-14-2, 18-17-15-14-3, 18-17-15-14-4, 18-17-15-14-5, 18-17-15-14-5A, 18-17-15-14-6, 18-17-15-14-7, 18-17-15-14-8, 18-17-15-14-8A, 18-17-15-14-9, 18-17-15-14-10, 18-17-15-14-10A, 18-17-15-14-11, 18-17-15-14-12, 18-17-15-14-13, which are group 17 compounds in groups 17-15-14-1 through 17-15-14-13 where R 9 is not —CH 2 —, (12) groups 18-17-16-14-1, 18-17-16-14-2, 18-17-16-14-3, 18-17-16-14-4, 18-17-16-14-5, 18-17-16-14-5A, 18-17-16-14-6, 18-17-16-14-7, 18-17-16-14-8, 18-17-16-14-8A, 18-17-16-14-9, 18-17-16-14-10, 18-17-16-14-10A, 18-17-16-14-11, 18-17-16-14-12, 18-17-16-14-13, which are group 17 compounds in groups 17-16-14-1 through 17-15-14-13 where R 9 is not —CH 2 —, (13) groups 18-17-16-15-1, 18-17-16-15-2, 18-17-16-15-3, 18-17-16-15-4, 18-17-16-15-5, 18-17-16-15-5A, 18-17-16-15-6, 18-17-16-15-7, 18-17-16-15-8, 18-17-16-15-8A, 18-17-16-15-9, 18-17-16-15-10, 18-17-16-15-10A, 18-17-16-15-11, 18-17-16-15-12 and 18-17-16-15-13, which are group 17 compounds in groups 17-16-15-1 through 17-16-15-13 where R 9 is not —CH 2 —, and (14) groups 18-17-16-15-14-1, 18-17-16-15-14-2, 18-17-16-15-14-3, 18-17-16-15-14-4, 18-17-16-15-14-5, 18-17-16-15-14-5A, 18-17-16-15-14-6, 18-17-16-15-14-7, 18-17-16-15-14-8, 18-17-16-15-14-8A, 18-17-16-15-14-9, 18-17-16-15-14-10, 18-17-16-15-14-10A, 18-17-16-15-14-11, 18-17-16-15-14-12 and 18-17-16-15-14-13, which are group 17 compounds in groups 17-16-15-14-1 through 17-16-15-14-13 where R 9 is not —CH 2 —.

Exemplary group 18 compounds include 2-oxa, 2-thia, 2-aza, 2α-optionally substituted alkyl analogs, 2, optionally substituted alkyl and, 2-(optionally substituted alkyl) 2 , e.g., —C(CH 3 ) 2 — or —C(CH 2 OH) 2 —, analogs of 3β-hydroxy-17β-aminoandrost-5-ene, 3α-hydroxy-17β-aminoandrost-5-ene, 3β-hydroxy-17α-aminoandrost-5-ene, 3β,70-dihydroxy-17β-aminoandrost-5-ene, 3β-hydroxy-17β-amino-19-norandrost-5-ene, 3α-hydroxy-17β-amino-19-norandrost-5-ene, 3β-hydroxy-16α-fluoro-17β-aminoandrost-5-ene, 3β-hydroxy-16α-fluoro-17β-aminoandrost-5-ene, 3β-hydroxy-17β-amino-19-norandrost-5-ene and any of the F1Cs or chemical structures disclosed herein.

Group 19. This group contains compounds in groups 1-18 above wherein R 8 is not —CH 2 — and is another R 8 moiety defined herein, e.g., —O—, —NH—, —N═, —S— or —C(R 10 ) 2 — where each R 10 is an independently chosen moiety described herein, where one R 10 is in the β-configuration and the other R 10 is in the α-configuration. Exemplary R 8 include —C(halogen) 2 - such as —CF 2 —, —CH(α-optionally substituted alkyl), —CH(, optionally substituted alkyl) or —C(optionally substituted alkyl) 2 - such as —C(CH 3 ) 2 — or —C(C 2 H 5 )(CH 3 )—. Each optionally substituted alkyl group can contain 1, 2, 3, 4, 5, 6, 7, 8 or more carbon atoms as defined previously. In some embodiments, when one or both R 10 at R 3 is —OH, —SH, ═O, an ester, a thioester, or another moiety that can give rise to a hydroxyl group by metabolism or hydrolysis, R 2 and/or R 10D is not —H.

These compounds include compounds in group 19-1 through 19-18-17-16-15-14-13, which collectively are group 19 compounds. These include groups 19-1, 19-2, 19-3, 19-4, 19-5, 19-5A, 19-6, 19-7, 19-8, 19-8A, 19-9, 19-10, 19-10A, 19-11, 19-12, 19-13, which are compounds in groups 1 through 13 where R 8 is not —CH 2 —. Group 19 compounds also include groups 19-14-1, 19-14-2, 19-14-3, 19-14-4, 19-14-5, 19-14-5A, 19-14-6, 19-14-7, 19-14-8, 19-14-8A, 19-14-9, 19-14-10, 19-14-10A, 19-14-11, 19-14-12 and 19-14-13, which are group 14 compounds in groups 14-1 through 14-13 where R 8 is not —CH 2 —.

Other group 19 compounds include (1) groups 19-15-1, 19-15-2, 19-15-3, 19-15-4, 19-15-5, 19-15-5A, 19-15-6, 19-15-7, 19-15-8, 19-15-8A, 19-15-9, 19-15-10, 19-15-10A, 19-15-11, 19-15-12 and 19-15-13, which are group 15 compounds in groups 15-1 through 15-13 where R 8 is not —CH 2 —, (2) groups 19-16-1, 19-16-2, 19-16-3, 19-16-4, 19-16-5, 19-16-5A, 19-16-6, 19-16-7, 19-16-8, 19-16-8A, 19-16-9, 19-16-10, 19-16-10A, 19-16-11, 19-16-12 and 19-16-13, which are group 16 compounds in groups 16-1 through 16-13 where R 8 is not —CH 2 —, (3) groups 19-17-1, 19-17-2, 19-17-3, 19-17-4, 19-17-5, 19-17-5A, 19-17-6, 19-17-7, 19-17-8, 19-17-8A, 19-17-9, 19-17-10, 19-17-10A, 19-17-11, 19-17-12 and 19-17-13, which are group 17 compounds in groups 17-1 through 17-13 where R 8 is not —CH 2 —, (4) groups 19-15-14-1, 19-15-14-2, 19-15-14-3, 19-15-14-4, 19-15-14-5, 19-15-14-5A, 19-15-14-6, 19-15-14-7, 19-15-14-8, 19-15-14-8A, 19-15-14-9, 19-15-14-10, 19-15-14-10A, 19-15-14-11, 19-15-14-12 and 19-15-14-13, which are group 15 compounds in groups 15-14-1 through 15-14-13 where R 8 is not —CH 2 —, (5) groups 19-16-14-1, 19-16-14-2, 19-16-14-3, 19-16-14-4, 19-16-14-5, 19-16-14-5A, 19-16-14-6, 19-16-14-7, 19-16-14-8, 19-16-14-8A, 19-16-14-9, 19-16-14-10, 19-16-14-10A, 19-16-14-11, 19-16-14-12 and 19-16-14-13, which are group 16 compounds in groups 16-14-1 through 16-14-13 where R 8 is not —CH 2 —, (6) groups 19-17-14-1, 19-17-14-2, 19-17-14-3, 19-17-14-4, 19-17-14-5, 19-17-14-5A, 19-17-14-6, 19-17-14-7, 19-17-14-8, 19-17-14-8A, 19-17-14-9, 19-17-14-10, 19-17-14-10A, 19-17-14-11, 19-17-14-12, 19-17-14-13, which are group 17 compounds in groups 17-14-1 through 17-14-13 where R 8 is not —CH 2 —, (7) groups 19-16-15-1, 19-16-15-2, 19-16-15-3, 19-16-15-4, 19-16-15-5, 19-16-15-5A, 19-16-15-6, 19-16-15-7, 19-16-15-8, 19-16-15-8A, 19-16-15-9, 19-16-15-10, 19-16-15-10A, 19-16-15-11, 19-16-15-12, 19-16-15-13, which are group 16 compounds in groups 16-15-1 through 16-15-13 where R 8 is not —CH 2 —, (8) groups 19-17-15-1, 19-17-15-2, 19-17-15-3, 19-17-15-4, 19-17-15-5, 19-17-15-5A, 19-17-15-6, 19-17-15-7, 19-17-15-8, 19-17-15-8A, 19-17-15-9, 19-17-15-10, 19-17-15-10A, 19-17-15-11, 19-17-15-12, 19-17-15-13, which are group 17 compounds in groups 17-15-1 through 17-15-13 where R 8 is not —CH 2 —, (9) groups 19-17-16-1, 19-17-16-2, 19-17-16-3, 19-17-16-4, 19-17-16-5, 19-17-16-5A, 19-17-16-6, 19-17-16-7, 19-17-16-8, 19-17-16-8A, 19-17-16-9, 19-17-16-10, 19-17-16-10A, 19-17-16-11, 19-17-16-12, 19-17-16-13, which are group 17 compounds in groups 17-16-1 through 17-16-13 where R 8 is not —CH 2 —, (10) groups 19-16-15-14-1, 19-16-15-14-2, 19-16-15-14-3, 19-16-15-14-4, 19-16-15-14-5, 19-16-15-14-5A, 19-16-15-14-6, 19-16-15-14-7, 19-16-15-14-8, 19-16-15-14-8A, 19-16-15-14-9, 19-16-15-14-10, 19-16-15-14-10A, 19-16-15-14-11, 19-16-15-14-12, 19-16-15-14-13, which are group 16 compounds in groups 16-15-14-1 through 16-15-14-13 where R 8 is not —CH 2 —, (11) groups 19-17-15-14-1, 19-17-15-14-2, 19-17-15-14-3, 19-17-15-14-4, 19-17-15-14-5, 19-17-15-14-5A, 19-17-15-14-6, 19-17-15-14-7, 19-17-15-14-8, 19-17-15-14-8A, 19-17-15-14-9, 19-17-15-14-10, 19-17-15-14-10A, 19-17-15-14-11, 19-17-15-14-12, 19-17-15-14-13, which are group 17 compounds in groups 17-15-14-1 through 17-15-14-13 where R 8 is not —CH 2 —, (12) groups 19-17-16-14-1, 19-17-16-14-2, 19-17-16-14-3, 19-17-16-14-4, 19-17-16-14-5, 19-17-16-14-5A, 19-17-16-14-6, 19-17-16-14-7, 19-17-16-14-8, 19-17-16-14-8A, 19-17-16-14-9, 19-17-16-14-10, 19-17-16-14-10A, 19-17-16-14-11, 19-17-16-14-12, 19-17-16-14-13, which are group 17 compounds in groups 17-16-14-1 through 17-15-14-13 where R 8 is not —CH 2 —, (13) groups 19-17-16-15-1, 19-17-16-15-2, 19-17-16-15-3, 19-17-16-15-4, 19-17-16-15-5, 19-17-16-15-5A, 19-17-16-15-6, 19-17-16-15-7, 19-17-16-15-8, 19-17-16-15-8A, 19-17-16-15-9, 19-17-16-15-10, 19-17-16-15-10A, 19-17-16-15-11, 19-17-16-15-12 and 19-17-16-15-13, which are group 17 compounds in groups 17-16-15-1 through 17-16-15-13 where R 8 is not —CH 2 —, (14) groups 19-17-16-15-14-1, 19-17-16-15-14-2, 19-17-16-15-14-3, 19-17-16-15-14-4, 19-17-16-15-14-5, 19-17-16-15-14-5A, 19-17-16-15-14-6, 19-17-16-15-14-7, 19-17-16-15-14-8, 19-17-16-15-14-8A, 19-17-16-15-14-9, 19-17-16-15-14-10, 19-17-16-15-14-10A, 19-17-16-15-14-11, 19-17-16-15-14-12 and 19-17-16-15-14-13, which are group 17 compounds in groups 17-16-15-14-1 through 17-16-15-14-13 where R 8 is not —CH 2 — and (15) all of the compounds and/or groups described in group 18 where R 8 is not —CH 2 —.

Exemplary group 19 compounds include 11-oxa, 11-thia, 11-aza, 11α-optionally substituted alkyl analogs, 11β-optionally substituted alkyl, 11-(optionally substituted alkyl) 2 , e.g., —C(CH 3 ) 2 — or —C(CH 2 OH) 2 —, analogs of 3β-hydroxy-17β-aminoandrost-5-ene, 2-oxa-3β-hydroxy-17β-aminoandrost-5-ene, 3α-hydroxy-17β-aminoandrost-5-ene, 3β-hydroxy-17α-aminoandrost-5-ene, 3β,7β-dihydroxy-17β-aminoandrost-5-ene, 3β-hydroxy-17β-amino-19-norandrost-5-ene, 3α-hydroxy-17β-amino-19-norandrost-5-ene, 3β-hydroxy-16α-fluoro-17β-aminoandrost-5-ene, 3β-hydroxy-16α-fluoro-17β-aminoandrost-5-ene, 3β-hydroxy-17β-amino-19-norandrost-5-ene and any of the F1Cs or chemical structures disclosed herein.

Group 20. This group contains compounds in groups 1-19 above wherein R 7 is not —CH 2 — and is another R 7 moiety defined herein, e.g., —O—, —NH—, —S— or —C(R 10 ) 2 — where each R 10 is an independently chosen moiety as defined herein. Exemplary R 7 include —C(halogen) 2 - such as —CF 2 —, —CH(α-OH), —CH(β-OH) or —C(optionally substituted alkyl) 2 -such as —C(CH 3 ) 2 — or —C(C 2 H 5 )(CH 3 )—. Each optionally substituted alkyl group can contain 1, 2, 3, 4, 5, 6, 7, 8 or more carbon atoms as defined previously.

These compounds include compounds in group 20-1 through 20-19-18-17-16-15-14-13, which collectively are group 19 compounds. These include groups 20-1, 20-2, 20-3, 20-4, 20-5, 20-5A, 20-6, 20-7, 20-8, 20-8A, 20-9, 20-10, 20-10A, 20-11, 20-12, 20-13, which are compounds in groups 1 through 13 where R 7 is not —CH 2 —. Group 20 compounds also include groups 20-14-1, 20-14-2, 20-14-3, 20-14-4, 20-14-5, 20-14-5A, 20-14-6, 20-14-7, 20-14-8, 20-14-8A, 20-14-9, 20-14-10, 20-14-10A, 20-14-11, 20-14-12 and 20-14-13, which are group 14 compounds in groups 14-1 through 14-13 where R 7 is not —CH 2 —.

Other group 20 compounds include (1) groups 20-15-1, 20-15-2, 20-15-3, 20-15-4, 20-15-5, 20-15-5A, 20-15-6, 20-15-7, 20-15-8, 20-15-8A, 20-15-9, 20-15-10, 20-15-10A, 20-15-11, 20-15-12 and 20-15-13, which are group 15 compounds in groups 15-1 through 15-13 where R 7 is not —CH 2 —, (2) groups 20-16-1, 20-16-2, 20-16-3, 20-16-4, 20-16-5, 20-16-5A, 20-16-6, 20-16-7, 20-16-8, 20-16-8A, 20-16-9, 20-16-10, 20-16-10A, 20-16-11, 20-16-12 and 20-16-13, which are group 16 compounds in groups 16-1 through 16-13 where R 7 is not —CH 2 —, (3) groups 20-17-1, 20-17-2, 20-17-3, 20-17-4, 20-17-5, 20-17-5A, 20-17-6, 20-17-7, 20-17-8, 20-17-8A, 20-17-9, 20-17-10, 20-17-10A, 20-17-11, 20-17-12 and 20-17-13, which are group 17 compounds in groups 17-1 through 17-13 where R 7 is not —CH 2 —, (4) groups 20-15-14-1, 20-15-14-2, 20-15-14-3, 20-15-14-4, 20-15-14-5, 20-15-14-5A, 20-15-14-6, 20-15-14-7, 20-15-14-8, 20-15-14-8A, 20-15-14-9, 20-15-14-10, 20-15-14-10A, 20-15-14-11, 20-15-14-12 and 20-15-14-13, which are group 15 compounds in groups 15-14-1 through 15-14-13 where R 7 is not —CH 2 —, (5) groups 20-16-14-1, 20-16-14-2, 20-16-14-3, 20-16-14-4, 20-16-14-5, 20-16-14-5A, 20-16-14-6, 20-16-14-7, 20-16-14-8, 20-16-14-8A, 20-16-14-9, 20-16-14-10, 20-16-14-10A, 20-16-14-11, 20-16-14-12 and 20-16-14-13, which are group 16 compounds in groups 16-14-1 through 16-14-13 where R 7 is not —CH 2 —, (6) groups 20-17-14-1, 20-17-14-2, 20-17-14-3, 20-17-14-4, 20-17-14-5, 20-17-14-5A, 20-17-14-6, 20-17-14-7, 20-17-14-8, 20-17-14-8A, 20-17-14-9, 20-17-14-10, 20-17-14-10A, 20-17-14-11, 20-17-14-12, 20-17-14-13, which are group 17 compounds in groups 17-14-1 through 17-14-13 where R 7 is not —CH 2 —, (7) groups 20-16-15-1, 20-16-15-2, 20-16-15-3, 20-16-15-4, 20-16-15-5, 20-16-15-5A, 20-16-15-6, 20-16-15-7, 20-16-15-8, 20-16-15-8A, 20-16-15-9, 20-16-15-10, 20-16-15-10A, 20-16-15-11, 20-16-15-12, 20-16-15-13, which are group 16 compounds in groups 16-15-1 through 16-15-13 where R 7 is not —CH 2 —, (8) groups 20-17-15-1, 20-17-15-2, 20-17-15-3, 20-17-15-4, 20-17-15-5, 20-17-15-5A, 20-17-15-6, 20-17-15-7, 20-17-15-8, 20-17-15-8A, 20-17-15-9, 20-17-15-10, 20-17-15-10A, 20-17-15-11, 20-17-15-12, 20-17-15-13, which are group 17 compounds in groups 17-15-1 through 17-15-13 where R 7 is not —CH 2 —, (9) groups 20-17-16-1, 20-17-16-2, 20-17-16-3, 20-17-16-4, 20-17-16-5, 20-17-16-5A, 20-17-16-6, 20-17-16-7, 20-17-16-8, 20-17-16-8A, 20-17-16-9, 20-17-16-10, 20-17-16-10A, 20-17-16-11, 20-17-16-12, 20-17-16-13, which are group 17 compounds in groups 17-16-1 through 17-16-13 where R 7 is not —CH 2 —, (10) groups 20-16-15-14-1, 20-16-15-14-2, 20-16-15-14-3, 20-16-15-14-4, 20-16-15-14-5, 20-16-15-14-5A, 20-16-15-14-6, 20-16-15-14-7, 20-16-15-14-8, 20-16-15-14-8A, 20-16-15-14-9, 20-16-15-14-10, 20-16-15-14-10A, 20-16-15-14-11, 20-16-15-14-12, 20-16-15-14-13, which are group 16 compounds in groups 16-15-14-1 through 16-15-14-13 where R 7 is not —CH 2 —, (11) groups 20-17-15-14-1, 20-17-15-14-2, 20-17-15-14-3, 20-17-15-14-4, 20-17-15-14-5, 20-17-15-14-5A, 20-17-15-14-6, 20-17-15-14-7, 20-17-15-14-8, 20-17-15-14-8A, 20-17-15-14-9, 20-17-15-14-10, 20-17-15-14-10A, 20-17-15-14-11, 20-17-15-14-12, 20-17-15-14-13, which are group 17 compounds in groups 17-15-14-1 through 17-15-14-13 where R 7 is not —CH 2 —, (12) groups 20-17-16-14-1, 20-17-16-14-2, 20-17-16-14-3, 20-17-16-14-4, 20-17-16-14-5, 20-17-16-14-5A, 20-17-16-14-6, 20-17-16-14-7, 20-17-16-14-8, 20-17-16-14-8A, 20-17-16-14-9, 20-17-16-14-10, 20-17-16-14-10A, 20-17-16-14-11, 20-17-16-14-12, 20-17-16-14-13, which are group 17 compounds in groups 17-16-14-1 through 17-15-14-13 where R 7 is not —CH 2 —, (13) groups 20-17-16-15-1, 20-17-16-15-2, 20-17-16-15-3, 20-17-16-15-4, 20-17-16-15-5, 20-17-16-15-5A, 20-17-16-15-6, 20-17-16-15-7, 20-17-16-15-8, 20-17-16-15-8A, 20-17-16-15-9, 20-17-16-15-10, 20-17-16-15-10A, 20-17-16-15-11, 20-17-16-15-12 and 20-17-16-15-13, which are group 17 compounds in groups 17-16-15-1 through 17-16-15-13 where R 7 is not —CH 2 —, (14) groups 20-17-16-15-14-1, 20-17-16-15-14-2, 20-17-16-15-14-3, 20-17-16-15-14-4, 20-17-16-15-14-5, 20-17-16-15-14-5A, 20-17-16-15-14-6, 20-17-16-15-14-7, 20-17-16-15-14-8, 20-17-16-15-14-8A, 20-17-16-15-14-9, 20-17-16-15-14-10, 20-17-16-15-14-10A, 20-17-16-15-14-11, 20-17-16-15-14-12 and 20-17-16-15-14-13, which are group 17 compounds in groups 17-16-15-14-1 through 17-16-15-14-13 where R 7 is not —CH 2 —, (15) all of the compounds and/or groups described in group 18 where R 7 is not —CH 2 — and (16) all of the compounds and/or groups described in group 19 where R 7 is not —CH 2 —.

Exemplary group 20 compounds include 15-oxa, 15-thia, 15-aza, 11α-optionally substituted alkyl analogs, 11β-optionally substituted alkyl, 15-(optionally substituted alkyl) 2 , e.g., —C(CH 3 ) 2 — or —C(CH 2 OH) 2 —, analogs of 3β-hydroxy-17β-aminoandrost-5-ene, 2-oxa-3β-hydroxy-17β-aminoandrost-5-ene, 3α-hydroxy-17β-aminoandrost-5-ene, 3β-hydroxy-17α-aminoandrost-5-ene, 3β,7β-dihydroxy-17β-aminoandrost-5-ene, 3β-hydroxy-17β-amino-19-norandrost-5-ene, 3α-hydroxy-17β-amino-19-norandrost-5-ene, 3β-hydroxy-16α-fluoro-17β-aminoandrost-5-ene, 3β-hydroxy-16α-fluoro-17β-aminoandrost-5-ene, 3β-hydroxy-17β-amino-19-norandrost-5-ene and any of the F1Cs or chemical structures disclosed herein.

Group 21. This group contains compounds in groups 1-20 above where R 4 substituents 1-10 listed in Table A are replaced with the following groups: 1-optionally substituted amine, 2-optionally substituted amide, 3-optionally substituted oxime, 4 -optionally substituted alkyl, 5-optionally substituted alkenyl, 6-optionally substituted alkynyl, 7-optionally substituted aryl, 8-optionally substituted heterocycle, 9-ether, e.g., methoxy, ethoxy or methoxymethyl and 10-ester, e.g., acetate, propionate, n-butyrate, i-butyrate, t-butyrate, enanthate or trifluoroacetate. Any of these groups can be a moiety defined herein for that group. Thus, for Table A substituent 1, optionally substituted amine, the R 4 group includes any optionally substituted amine moieties described herein such as —NH 2 , —NH 3 + Cl − , —NH 3 + Br − , —NH 3 + I − , optionally substituted alkylamine, di-optionally substituted alkylamine, —NHR PR , —N(R PR ) 2 , —NH—CH 3 , —N(CH 3 ) 2 , —N(C 2 H 5 ) 2 , —N(n-propyl) 2 , —N(i-propyl) 2 , —N(n-butyl) 2 , —N(t-butyl) 2 , —NH—C 1-4 alkyl, —NH—C 1-4 hydroxyalkyl, —NH—C 1-4 fluoroalkyl, —NH—C 5-8 alkyl, —NH—C 5-8 hydroxyalkyl, —NH—C 5-8 fluoroalkyl, —NH—C 5-8 (halo) n -alkyl where n is 1, 2, 3, 4, 5, 6, 7 or 8 and the halogens are the same or different, —NH—CH 2 —CH 2 —C(O)—OH or a salt, —NH—CH 2 —CH 2 —C(O)—OCH 3 , —NH—CH 2 —CH 2 —O—C(O)—OCH 3 and —NH—CH 2 —CH 2 —O—CH 3 , where R PR are independently selected protecting groups and any alkyl group contains 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more carbon atoms and is optionally substituted as described herein. Similarly, optionally substituted amide includes moieties such as —C(O)—NH 2 , —NH—C(O)—CH 3 , —NH—C(O)—CF 3 , —NH—C(O)—C 2 H 5 , —C(O)—NH—C(CH 3 ) 3 and —C(O)—NH 2 , which are described herein. Other R 4 moieties include ═N—OCH 3 , ═N—OC 2 H 5 , ═N—OC 3 H 7 and ═N—O-optionally substituted alkyl, —NH 2 , —NHCH 3 , —N(CH 3 ) 2 , —NHC 2 H 5 , —N(C 2 H 5 ) 2 , —NHC 3 H 7 , —N(C 3 H 7 ) 2 , —NHC 4 H 9 , —N(C 4 H 9 ) 2 , —NH-optionally substituted alkyl, —N(optionally substituted alkyl) 2 , —NH—C 6 H 5 , —N(C 6 H 5 ) 2 , —NH-optionally substituted monosaccharide —NH-optionally substituted oligosaccharide, —NHC(O)-optionally substituted alkyl, —N(CH 3 )—C(O)-optionally substituted alkyl, —N(C 2 H 5 )—C(O)-optionally substituted alkyl, —N(C 3 H 7 )—C(O)-optionally substituted alkyl, —N(C 4 H 9 )—C(O)-optionally substituted alkyl, —N(C 6 H 5 )—C(O)-optionally substituted alkyl, —NH—C(O)-optionally substituted monosaccharide and —NH—C(O)-optionally substituted oligosaccharide, where alkyl or phenyl groups are the same or different and are optionally substituted as described herein.

These compounds include compounds in group 21-1 through 21-20-19-18-17-16-15-14-13, which collectively are group 21 compounds. These include groups 21-1, 21-2, 21-3, 21-4, 21-5, 21-5A, 21-6, 21-7, 21-8, 21-8A, 21-9, 21-10, 21-10A, 21-11, 21-12, 21-13, which are compounds in groups 1 through 13 where R 4 substituents 1-10 in Table A are replaced with the moieties given in this group. Group 21 compounds also include groups 21-14-1, 21-14-2, 21-14-3, 21-14-4, 21-14-5, 21-14-5A, 21-14-6, 21-14-7, 21-14-8, 21-14-8A, 21-14-9, 21-14-10, 21-14-10A, 21-14-11, 21-14-12 and 21-14-13, which are group 14 compounds in groups 14-1 through 14-13 where R 4 substituents 1-10 in Table A are replaced with the moieties given in this group.

Other group 21 compounds include (1) groups 21-15-1, 21-15-2, 21-15-3, 21-15-4, 21-15-5, 21-15-5A, 21-15-6, 21-15-7, 21-15-8, 21-15-8A, 21-15-9, 21-15-10, 21-15-10A, 21-15-11, 21-15-12 and 21-15-13, which are group 15 compounds in groups 15-1 through 15-13, (2) groups 21-16-1, 21-16-2, 21-16-3, 21-16-4, 21-16-5, 21-16-5A, 21-16-6, 21-16-7, 21-16-8, 21-16-8A, 21-16-9, 21-16-10, 21-16-10A, 21-16-11, 21-16-12 and 21-16-13, which are group 16 compounds in groups 16-1 through 16-13, (3) groups 21-17-1, 21-17-2, 21-17-3, 21-17-4, 21-17-5, 21-17-5A, 21-17-6, 21-17-7, 21-17-8, 21-17-8A, 21-17-9, 21-17-10, 21-17-10A, 21-17-11, 21-17-12 and 21-17-13, which are group 17 compounds in groups 17-1 through 17-13, (4) groups 21-15-14-1, 21-15-14-2, 21-15-14-3, 21-15-14-4, 21-15-14-5, 21-15-14-5A, 21-15-14-6, 21-15-14-7, 21-15-14-8, 21-15-14-8A, 21-15-14-9, 21-15-14-10, 21-15-14-10A, 21-15-14-11, 21-15-14-12 and 21-15-14-13, which are group 15 compounds in groups 15-14-1 through 15-14-13, (5) groups 21-16-14-1, 21-16-14-2, 21-16-14-3, 21-16-14-4, 21-16-14-5, 21-16-14-5A, 21-16-14-6, 21-16-14-7, 21-16-14-8, 21-16-14-8A, 21-16-14-9, 21-16-14-10, 21-16-14-10A, 21-16-14-11, 21-16-14-12 and 21-16-14-13, which are group 16 compounds in groups 16-14-1 through 16-14-13, (6) groups 21-17-14-1, 21-17-14-2, 21-17-14-3, 21-17-14-4, 21-17-14-5, 21-17-14-5A, 21-17-14-6, 21-17-14-7, 21-17-14-8, 21-17-14-8A, 21-17-14-9, 21-17-14-10, 21-17-14-10A, 21-17-14-11, 21-17-14-12, 21-17-14-13, which are group 17 compounds in groups 17-14-1 through 17-14-13, (7) groups 21-16-15-1, 21-16-15-2, 21-16-15-3, 21-16-15-4, 21-16-15-5, 21-16-15-5A, 21-16-15-6, 21-16-15-7, 21-16-15-8, 21-16-15-8A, 21-16-15-9, 21-16-15-10, 21-16-15-10A, 21-16-15-11, 21-16-15-12, 21-16-15-13, which are group 16 compounds in groups 16-15-1 through 16-15-13, (8) groups 21-17-15-1, 21-17-15-2, 21-17-15-3, 21-17-15-4, 21-17-15-5, 21-17-15-5A, 21-17-15-6, 21-17-15-7, 21-17-15-8, 21-17-15-8A, 21-17-15-9, 21-17-15-10, 21-17-15-10A, 21-17-15-11, 21-17-15-12, 21-17-15-13, which are group 17 compounds in groups 17-15-1 through 17-15-13, (9) groups 21-17-16-1, 21-17-16-2, 21-17-16-3, 21-17-16-4, 21-17-16-5, 21-17-16-5A, 21-17-16-6, 21-17-16-7, 21-17-16-8, 21-17-16-8A, 21-17-16-9, 21-17-16-10, 21-17-16-10A, 21-17-16-11, 21-17-16-12, 21-17-16-13, which are group 17 compounds in groups 17-16-1 through 17-16-13, (10) groups 21-16-15-14-1, 21-16-15-14-2, 21-16-15-14-3, 21-16-15-14-4, 21-16-15-14-5, 21-16-15-14-5A, 21-16-15-14-6, 21-16-15-14-7, 21-16-15-14-8, 21-16-15-14-8A, 21-16-15-14-9, 21-16-15-14-10, 21-16-15-14-10A, 21-16-15-14-11, 21-16-15-14-12, 21-16-15-14-13, which are group 16 compounds in groups 16-15-14-1 through 16-15-14-13, (11) groups 21-17-15-14-1, 21-17-15-14-2, 21-17-15-14-3, 21-17-15-14-4, 21-17-15-14-5, 21-17-15-14-5A, 21-17-15-14-6, 21-17-15-14-7, 21-17-15-14-8, 21-17-15-14-8A, 21-17-15-14-9, 21-17-15-14-10, 21-17-15-14-10A, 21-17-15-14-11, 21-17-15-14-12, 21-17-15-14-13, which are group 17 compounds in groups 17-15-14-1 through 17-15-14-13, (12) groups 21-17-16-14-1, 21-17-16-14-2, 21-17-16-14-3, 21-17-16-14-4, 21-17-16-14-5, 21-17-16-14-5A, 21-17-16-14-6, 21-17-16-14-7, 21-17-16-14-8, 21-17-16-14-8A, 21-17-16-14-9, 21-17-16-14-10, 21-17-16-14-10A, 21-17-16-14-11, 21-17-16-14-12, 21-17-16-14-13, which are group 17 compounds in groups 17-16-14-1 through 17-15-14-13, (13) groups 21-17-16-15-1, 21-17-16-15-2, 21-17-16-15-3, 21-17-16-15-4, 21-17-16-15-5, 21-17-16-15-5A, 21-17-16-15-6, 21-17-16-15-7, 21-17-16-15-8, 21-17-16-15-8A, 21-17-16-15-9, 21-17-16-15-10, 21-17-16-15-10A, 21-17-16-15-11, 21-17-16-15-12 and 21-17-16-15-13, which are group 17 compounds in groups 17-16-15-1 through 17-16-15-13, (14) groups 21-17-16-15-14-1, 21-17-16-15-14-2, 21-17-16-15-14-3, 21-17-16-15-14-4, 21-17-16-15-14-5, 21-17-16-15-14-5A, 21-17-16-15-14-6, 21-17-16-15-14-7, 21-17-16-15-14-8, 21-17-16-15-14-8A, 21-17-16-15-14-9, 21-17-16-15-14-10, 21-17-16-15-14-10A, 21-17-16-15-14-11, 21-17-16-15-14-12 and 21-17-16-15-14-13, which are group 17 compounds in groups 17-16-15-14-1 through 17-16-15-14-13, (15) all of the compounds and/or groups described in group 18, (16) all of the compounds and/or groups described in group 19 and (17) all of the compounds and/or groups described in group 20.

Exemplary group 21 compounds include 3β-hydroxy-17β-methylaminoandrost-5-ene, 3β-hydroxy-17β-methylamino-5α-androstane, 3α-hydroxy-17β-methylamino-5α-androstane, 3β-hydroxy-17β-methylamino-5β-androstane, 3β-hydroxy-17β-methylamino-5β-androst-1-ene, 3α-hydroxy-17β-methylamino-5β-androst-1-ene, 3β-hydroxy-17α-methylamino-5β-androst-1-ene, 3β-hydroxy-17β-methylamino-5α-androst-1-ene, 3β-hydroxy-17β-methylamino-5α, 14β-androst-1-ene, 3β-hydroxy-17β-methylamino-5α, 14β-androstane, 3β-hydroxy-17β-hydroxyaminoandrost-5-ene, 3β-hydroxy-17β-methylaminoandrost-1,5-diene, 3β-hydroxy-17β-methylaminoandrost-4-ene, 2-oxa-3β-hydroxy-17β-methylaminoandrost-5-ene, 3α-hydroxy-17β-methylaminoandrost-5-ene, 3β-hydroxy-17α-methylaminoandrost-5-ene, 3β,7β-dihydroxy-17β-ethylaminoandrost-5-ene, 3β-hydroxy-17β-methylamino-19-norandrost-5-ene, 3α-hydroxy-17β-methylamino-19-norandrost-5-ene, 3β-hydroxy-16α-fluoro-17β-methylaminoandrost-5-ene, 3β-hydroxy-16α-fluoro-17β-methylaminoandrost-1,4-diene, 3β-hydroxy-17β-dimethylamino-19-norandrost-5-ene, analogs of any of these compounds where the methyl or ethyl group is substituted, e.g., with —OH, halogen or —C(O)OR PR

Group 22. This group contains compounds in groups 1-20 above where R 4 substituents 1-10 listed in Table A are replaced with the following groups: 1-acyl, 2-thioester, 3-thioether, 4-thioacyl, 5-epoxide, 6-optionally substituted cyclopropyl, 7 —O—Si(C1-C6 alkyl) 3 , 8-phosphate, 9-phosphate ester, and 10-phosphate ether. Any of these groups can be a moiety defined herein for that group. Thus, for Table A substituent 1, acyl, the R 4 group includes moieties such as —C(O)CH 3 , —C(O)C 2 H 5 , —C(O)CH 2 OH, —C(O)CH 2 -halogen and —C(O)-optionally substituted alkyl. Similarly, thioester includes moieties such as —C(O)—SCH 3 , —C(O)—SC 2 H 5 , —S—C(O)-optionally substituted alkyl and —C(O)—S-optionally substituted alkyl. The epoxide and optionally substituted cyclopropyl moieties for substituents 5 and 6 respectively can be at the 16-17 positions or at the 17-18 positions. For any ionizable moiety in this group, e.g., phosphate, or any other group disclosed herein, e.g., optionally substituted carboxyl in group 23 below, the moiety can be present as the free moiety, e.g., sulfate, phosphate, carboxyl or amine, or it may be present as a salt with a suitable counter ion, e.g., any ion disclosed herein such as F − , Cl − , I − , Ca ++ , NH 4 + , Na + or K + .

These compounds include compounds in group 22-1 through 22-20-19-18-17-16-15-14-13, which collectively are group 22 compounds. These include groups 22-1, 22-2, 22-3, 22-4, 22-5, 22-5A, 22-6, 22-7, 22-8, 22-8A, 22-9, 22-10, 22-10A, 22-11, 22-12, 22-13, which are compounds in groups 1 through 13 where R 4 substituents 1-10 in Table A are replaced with the moieties given in this group. Group 22 compounds also include groups 22-14-1, 22-14-2, 22-14-3, 22-14-4, 22-14-5, 22-14-5A, 22-14-6, 22-14-7, 22-14-8, 22-14-8A, 22-14-9, 22-14-10, 22-14-10A, 22-14-11, 22-14-12 and 22-14-13, which are group 14 compounds in groups 14-1 through 14-13 where R 4 substituents 1-10 in Table A are replaced with the moieties given in this group.

Other group 22 compounds include (1) groups 22-15-1, 22-15-2, 22-15-3, 22-15-4, 22-15-5, 22-15-5A, 22-15-6, 22-15-7, 22-15-8, 22-15-8A, 22-15-9, 22-15-10, 22-15-10A, 22-15-11, 22-15-12 and 22-15-13, which are group 15 compounds in groups 15-1 through 15-13, (2) groups 22-16-1, 22-16-2, 22-16-3, 22-16-4, 22-16-5, 22-16-5A, 22-16-6, 22-16-7, 22-16-8, 22-16-8A, 22-16-9, 22-16-10, 22-16-10A, 22-16-11, 22-16-12 and 22-16-13, which are group 16 compounds in groups 16-1 through 16-13, (3) groups 22-17-1, 22-17-2, 22-17-3, 22-17-4, 22-17-5, 22-17-5A, 22-17-6, 22-17-7, 22-17-8, 22-17-8A, 22-17-9, 22-17-10, 22-17-10A, 22-17-11, 22-17-12 and 22-17-13, which are group 17 compounds in groups 17-1 through 17-13, (4) groups 22-15-14-1, 22-15-14-2, 22-15-14-3, 22-15-14-4, 22-15-14-5, 22-15-14-5A, 22-15-14-6, 22-15-14-7, 22-15-14-8, 22-15-14-8A, 22-15-14-9, 22-15-14-10, 22-15-14-10A, 22-15-14-11, 22-15-14-12 and 22-15-14-13, which are group 15 compounds in groups 15-14-1 through 15-14-13, (5) groups 22-16-14-1, 22-16-14-2, 22-16-14-3, 22-16-14-4, 22-16-14-5, 22-16-14-5A, 22-16-14-6, 22-16-14-7, 22-16-14-8, 22-16-14-8A, 22-16-14-9, 22-16-14-10, 22-16-14-10A, 22-16-14-11, 22-16-14-12 and 22-16-14-13, which are group 16 compounds in groups 16-14-1 through 16-14-13, (6) groups 22-17-14-1, 22-17-14-2, 22-17-14-3, 22-17-14-4, 22-17-14-5, 22-17-14-5A, 22-17-14-6, 22-17-14-7, 22-17-14-8, 22-17-14-8A, 22-17-14-9, 22-17-14-10, 22-17-14-10A, 22-17-14-11, 22-17-14-12, 22-17-14-13, which are group 17 compounds in groups 17-14-1 through 17-14-13, (7) groups 22-16-15-1, 22-16-15-2, 22-16-15-3, 22-16-15-4, 22-16-15-5, 22-16-15-5A, 22-16-15-6, 22-16-15-7, 22-16-15-8, 22-16-15-8A, 22-16-15-9, 22-16-15-10, 22-16-15-10A, 22-16-15-11, 22-16-15-12, 22-16-15-13, which are group 16 compounds in groups 16-15-1 through 16-15-13, (8) groups 22-17-15-1, 22-17-15-2, 22-17-15-3, 22-17-15-4, 22-17-15-5, 22-17-15-5A, 22-17-15-6, 22-17-15-7, 22-17-15-8, 22-17-15-8A, 22-17-15-9, 22-17-15-10, 22-17-15-10A, 22-17-15-11, 22-17-15-12, 22-17-15-13, which are group 17 compounds in groups 17-15-1 through 17-15-13, (9) groups 22-17-16-1, 22-17-16-2, 22-17-16-3, 22-17-16-4, 22-17-16-5, 22-17-16-5A, 22-17-16-6, 22-17-16-7, 22-17-16-8, 22-17-16-8A, 22-17-16-9, 22-17-16-10, 22-17-16-10A, 22-17-16-11, 22-17-16-12, 22-17-16-13, which are group 17 compounds in groups 17-16-1 through 17-16-13, (10) groups 22-16-15-14-1, 22-16-15-14-2, 22-16-15-14-3, 22-16-15-14-4, 22-16-15-14-5, 22-16-15-14-5A, 22-16-15-14-6, 22-16-15-14-7, 22-16-15-14-8, 22-16-15-14-8A, 22-16-15-14-9, 22-16-15-14-10, 22-16-15-14-10A, 22-16-15-14-11, 22-16-15-14-12, 22-16-15-14-13, which are group 16 compounds in groups 16-15-14-1 through 16-15-14-13, (11) groups 22-17-15-14-1, 22-17-15-14-2, 22-17-15-14-3, 22-17-15-14-4, 22-17-15-14-5, 22-17-15-14-5A, 22-17-15-14-6, 22-17-15-14-7, 22-17-15-14-8, 22-17-15-14-8A, 22-17-15-14-9, 22-17-15-14-10, 22-17-15-14-10A, 22-17-15-14-11, 22-17-15-14-12, 22-17-15-14-13, which are group 17 compounds in groups 17-15-14-1 through 17-15-14-13, (12) groups 22-17-16-14-1, 22-17-16-14-2, 22-17-16-14-3, 22-17-16-14-4, 22-17-16-14-5, 22-17-16-14-5A, 22-17-16-14-6, 22-17-16-14-7, 22-17-16-14-8, 22-17-16-14-8A, 22-17-16-14-9, 22-17-16-14-10, 22-17-16-14-10A, 22-17-16-14-11, 22-17-16-14-12, 22-17-16-14-13, which are group 17 compounds in groups 17-16-14-1 through 17-15-14-13, (13) groups 22-17-16-15-1, 22-17-16-15-2, 22-17-16-15-3, 22-17-16-15-4, 22-17-16-15-5, 22-17-16-15-5A, 22-17-16-15-6, 22-17-16-15-7, 22-17-16-15-8, 22-17-16-15-8A, 22-17-16-15-9, 22-17-16-15-10, 22-17-16-15-10A, 22-17-16-15-11, 22-17-16-15-12 and 22-17-16-15-13, which are group 17 compounds in groups 17-16-15-1 through 17-16-15-13, (14) groups 22-17-16-15-14-1, 22-17-16-15-14-2, 22-17-16-15-14-3, 22-17-16-15-14-4, 22-17-16-15-14-5, 22-17-16-15-14-5A, 22-17-16-15-14-6, 22-17-16-15-14-7, 22-17-16-15-14-8, 22-17-16-15-14-8A, 22-17-16-15-14-9, 22-17-16-15-14-10, 22-17-16-15-14-10A, 22-17-16-15-14-11, 22-17-16-15-14-12 and 22-17-16-15-14-13, which are group 17 compounds in groups 17-16-15-14-1 through 17-16-15-14-13, (15) all of the compounds and/or groups described in group 18, (16) all of the compounds and/or groups described in group 19 and (17) all of the compounds and/or groups described in group 20.

Exemplary phosphate and phosphate esters include 3β-hydroxyandrost-5-ene-17β-phosphate, 3α-hydroxyandrost-5-ene-17β-phosphate, 3β-hydroxy-16α-fluoroandrost-5-ene-17β-phosphate, 3α-hydroxy-16α-fluoroandrost-5-ene-17β-phosphate, 3β-hydroxy-5α-androstane-17β-phosphate, 3α-hydroxy-5α-androstane-17β-phosphate, 3β-hydroxy-5β-androstane-17β-phosphate, 3α-hydroxy-5β-androstane-17β-phosphate, 3β-hydroxy-5α, 14β-androstane-17β-phosphate, 3α-hydroxy-5α, 14β-androstane-17β-phosphate, 3β-hydroxy-5β, 14β-androstane-17β-phosphate, 3β-hydroxy-5β, 14β-androstane-17α-phosphate, or a salt, 2-oxa analog, 1α-alkyl, 4α-optionally substituted alkyl, 7-substituted analog, 16α-halo, 16α-hydroxy, 19-nor or phosphate ester, e.g., phosphate methyl ester (—O—P(O)(O)—OCH 3 ), phosphate ethyl ester or phosphate optionally substituted alkyl ester of any of these compounds.

Group 23. This group contains compounds in groups 1-20 above where R 4 substituents 1-10 listed in Table A are replaced with the following groups: 1-phosphate thioether, 2-thionoester, 3-amino acid, 4-peptide, 5-dipeptide, 6-optionally substituted heterocycle, 7-optionally substituted carboxyl, e.g., —COOH, —COOCH 3 , —COOC 2 H 5 , —COOR PR or —COO − Na + , 8-carbonate, e.g., optionally substituted alkylcarbonate such as —O—C(O)—OCH 3 or —O—C(O)—OC 2 H 5 , 9-carbamate and 10 -phosphothioester or a salt, e.g., Na + or K + .

Amino acids for substituent 3 are as described herein and include, e.g., —NH—CH 2 —C(O)OH, —NH—CH 2 —C(O)OR PR , —NH—CH 2 —CH 2 —C(O)OH, —NH—CH 2 —CH 2 —C(O)OR PR , —NH—CH(CH 3 )—C(O)OH, —NH—CH(CH 3 )—CH 2 —C(O)OH, —NH—CH(CH 3 )—CH 2 —C(O)OR PR , —NH—CH 2 —CH 2 —CH 2 —C(O)OH—NH—CH 2 —CH 2 —C—C(O)—CH 2 —NH 2 C—O—C(O)—CH 2 —NHR PR , —O—C(O)—CH 2 —CH 2 —NH 2 , —O—C(O)—CH 2 —CH 2 —NHR PR or for ionizable groups such as free carboxyls or amines, a salt such as a Na + or K + salt for carboxyls or a salt such as HCl or HBr salt for amines. Carbonates for substituent 8 are as described herein, e.g., —O—C(O)—OH, —O—C(O)—OCH 3 , —O—C(O)—OCH 2 OH, —O—C(O)—OCH 2 F, —O—C(O)—OC 2 H 5 , —O—C(O)—OC 3 H 7 , —O—C(O)—OC 4 H 9 , —O—C(O)—O-optionally substituted alkyl, —O—C(O)—O-optionally substituted alkenyl, or —O—C(O)—O-optionally substituted monosaccharide. Carbamates for substituent 9 are as described herein, e.g., —NH—C(O)—OCH 3 , —NH—C(O)—OC 2 H 5 , —NH—C(O)—OC 3 H 7 , —NH—C(O)—OC 4 H 9 , —NH—C(O)—OC 6 H 13 , —NH—C(O)—OC 6 H 5 , —NH—C(O)—OC 6 H 4 —C(O)OR PR , —NH—C(O)—OCH 2 OH, —NH—C(O)—OCH 2 C(O)OH, —NH—C(O)—OCH 2 -halogen, —NH—C(O)—OCHOH—CH 3 , —NH—C(O)—O(CH 2 ) n —OH, —NH—C(O)—OCH(CH 3 )—(CH 2 ) n —OH, —NH—C(O)—OCH(CH 3 )—(CH 2 ) n —C(O)OH, —NH—C(O)—O(CH 2 ) n -halogen, —NH—C(O)—O(CH 2 ) n —NH 2 , —NH—C(O)—O(CH 2 ) n —NHR PR , —NH—C(O)—O(CH 2 ) n —C(O)OH, —NH—C(O)—OC 3 H 6 OH —NH—C(O)—OC 6 H 4 —F, —NH—C(O)—O-optionally substituted alkyl, —NH—C(O)—O-optionally substituted alkenyl, —NH—C(O)—O-heterocycle or —NH—C(O)—O-optionally substituted monosaccharide, where n is 1, 2, 3, 4, 5 or 6. Any of these alkyl or alkenyl groups may contain 1, 2, 3, 4, 5, 6, 7, 8, 9,  or more atoms. Exemplary group 23 compounds include 3β-hydroxyandrost-5-ene-17β-carbamate, 3β-hydroxyandrost-1,5-diene-17β-carbamate, 3α-hydroxyandrost-5-ene-17β-carbamate, 3β-hydroxyandrost-5-ene-17α-carbamate, 3α-hydroxyandrost-5-ene-17α-carbamate, 3β-hydroxyandrost-4-ene-17β-carbamate, 3α-hydroxyandrost-4-ene-17β-carbamate, 3α-hydroxyandrost-1,4-diene-17β-carbamate, 3β-hydroxyandrost-1,5,16-triene-17-carbamate, and analogs of any of these compounds having one, two or more moieties such as 16α-halo, 16α-fluoro, 16β-fluoro, 16-fluoro, 16α-hydroxy, 7α-hydroxy or thiol, 7β-hydroxy or thiol, 7-oxo, 7α-halo, 7β-halo, 7α-fluoro, 7β-fluoro, 7α-alkoxy, 7β-alkoxy, 4α-halo, 4β-halo, 4α-alkyl, 4β-alkyl, 12α-halo, 12β-halo, 12α-alkyl, 12β-alkyl, 11-dihalo, 11-dialkyl, 2-oxa, 11-oxa, 19-nor or the like.

These compounds include compounds in group 23-1 through 23-20-19-18-17-16-15-14-13, which collectively are group 23 compounds. These include groups 23-1, 23-2, 23-3, 23-4, 23-5, 23-5A, 23-6, 23-7, 23-8, 23-8A, 23-9, 23-10, 23-10A, 23-11, 23-12, 23-13, which are compounds in groups 1 through 13 where R 4 substituents 1-10 in Table A are replaced with the moieties given in this group. Group 23 compounds also include groups 23-14-1, 23-14-2, 23-14-3, 23-14-4, 23-14-5, 23-14-5A, 23-14-6, 23-14-7, 23-14-8, 23-14-8A, 23-14-9, 23-14-10, 23-14-10A, 23-14-11, 23-14-12 and 23-14-13, which are group 14 compounds in groups 14-1 through 14-13 where R 4 substituents 1-10 in Table A are replaced with the moieties given in this group.

Other group 23 compounds include (1) groups 23-15-1, 23-15-2, 23-15-3, 23-15-4, 23-15-5, 23-15-5A, 23-15-6, 23-15-7, 23-15-8, 23-15-8A, 23-15-9, 23-15-10, 23-15-10A, 23-15-11, 23-15-12 and 23-15-13, which are group 15 compounds in groups 15-1 through 15-13, (2) groups 23-16-1, 23-16-2, 23-16-3, 23-16-4, 23-16-5, 23-16-5A, 23-16-6, 23-16-7, 23-16-8, 23-16-8A, 23-16-9, 23-16-10, 23-16-10A, 23-16-11, 23-16-12 and 23-16-13, which are group 16 compounds in groups 16-1 through 16-13, (3) groups 23-17-1, 23-17-2, 23-17-3, 23-17-4, 23-17-5, 23-17-5A, 23-17-6, 23-17-7, 23-17-8, 23-17-8A, 23-17-9, 23-17-10, 23-17-10A, 23-17-11, 23-17-12 and 23-17-13, which are group 17 compounds in groups 17-1 through 17-13, (4) groups 23-15-14-1, 23-15-14-2, 23-15-14-3, 23-15-14-4, 23-15-14-5, 23-15-14-5A, 23-15-14-6, 23-15-14-7, 23-15-14-8, 23-15-14-8A, 23-15-14-9, 23-15-14-10, 23-15-14-10A, 23-15-14-11, 23-15-14-12 and 23-15-14-13, which are group 15 compounds in groups 15-14-1 through 15-14-13, (5) groups 23-16-14-1, 23-16-14-2, 23-16-14-3, 23-16-14-4, 23-16-14-5, 23-16-14-5A, 23-16-14-6, 23-16-14-7, 23-16-14-8, 23-16-14-8A, 23-16-14-9, 23-16-14-10, 23-16-14-10A, 23-16-14-11, 23-16-14-12 and 23-16-14-13, which are group 16 compounds in groups 16-14-1 through 16-14-13, (6) groups 23-17-14-1, 23-17-14-2, 23-17-14-3, 23-17-14-4, 23-17-14-5, 23-17-14-5A, 23-17-14-6, 23-17-14-7, 23-17-14-8, 23-17-14-8A, 23-17-14-9, 23-17-14-10, 23-17-14-10A, 23-17-14-11, 23-17-14-12, 23-17-14-13, which are group 17 compounds in groups 17-14-1 through 17-14-13, (7) groups 23-16-15-1, 23-16-15-2, 23-16-15-3, 23-16-15-4, 23-16-15-5, 23-16-15-5A, 23-16-15-6, 23-16-15-7, 23-16-15-8, 23-16-15-8A, 23-16-15-9, 23-16-15-10, 23-16-15-10A, 23-16-15-11, 23-16-15-12, 23-16-15-13, which are group 16 compounds in groups 16-15-1 through 16-15-13, (8) groups 23-17-15-1, 23-17-15-2, 23-17-15-3, 23-17-15-4, 23-17-15-5, 23-17-15-5A, 23-17-15-6, 23-17-15-7, 23-17-15-8, 23-17-15-8A, 23-17-15-9, 23-17-15-10, 23-17-15-10A, 23-17-15-11, 23-17-15-12, 23-17-15-13, which are group 17 compounds in groups 17-15-1 through 17-15-13, (9) groups 23-17-16-1, 23-17-16-2, 23-17-16-3, 23-17-16-4, 23-17-16-5, 23-17-16-5A, 23-17-16-6, 23-17-16-7, 23-17-16-8, 23-17-16-8A, 23-17-16-9, 23-17-16-10, 23-17-16-10A, 23-17-16-11, 23-17-16-12, 23-17-16-13, which are group 17 compounds in groups 17-16-1 through 17-16-13, (10) groups 23-16-15-14-1, 23-16-15-14-2, 23-16-15-14-3, 23-16-15-14-4, 23-16-15-14-5, 23-16-15-14-5A, 23-16-15-14-6, 23-16-15-14-7, 23-16-15-14-8, 23-16-15-14-8A, 23-16-15-14-9, 23-16-15-14-10, 23-16-15-14-10A, 23-16-15-14-11, 23-16-15-14-12, 23-16-15-14-13, which are group 16 compounds in groups 16-15-14-1 through 16-15-14-13, (11) groups 23-17-15-14-1, 23-17-15-14-2, 23-17-15-14-3, 23-17-15-14-4, 23-17-15-14-5, 23-17-15-14-5A, 23-17-15-14-6, 23-17-15-14-7, 23-17-15-14-8, 23-17-15-14-8A, 23-17-15-14-9, 23-17-15-14-10, 23-17-15-14-10A, 23-17-15-14-11, 23-17-15-14-12, 23-17-15-14-13, which are group 17 compounds in groups 17-15-14-1 through 17-15-14-13, (12) groups 23-17-16-14-1, 23-17-16-14-2, 23-17-16-14-3, 23-17-16-14-4, 23-17-16-14-5, 23-17-16-14-5A, 23-17-16-14-6, 23-17-16-14-7, 23-17-16-14-8, 23-17-16-14-8A, 23-17-16-14-9, 23-17-16-14-10, 23-17-16-14-10A, 23-17-16-14-11, 23-17-16-14-12, 23-17-16-14-13, which are group 17 compounds in groups 17-16-14-1 through 17-15-14-13, (13) groups 23-17-16-15-1, 23-17-16-15-2, 23-17-16-15-3, 23-17-16-15-4, 23-17-16-15-5, 23-17-16-15-5A, 23-17-16-15-6, 23-17-16-15-7, 23-17-16-15-8, 23-17-16-15-8A, 23-17-16-15-9, 23-17-16-15-10, 23-17-16-15-10A, 23-17-16-15-11, 23-17-16-15-12 and 23-17-16-15-13, which are group 17 compounds in groups 17-16-15-1 through 17-16-15-13, (14) groups 23-17-16-15-14-1, 23-17-16-15-14-2, 23-17-16-15-14-3, 23-17-16-15-14-4, 23-17-16-15-14-5, 23-17-16-15-14-5A, 23-17-16-15-14-6, 23-17-16-15-14-7, 23-17-16-15-14-8, 23-17-16-15-14-8A, 23-17-16-15-14-9, 23-17-16-15-14-10, 23-17-16-15-14-10A, 23-17-16-15-14-11, 23-17-16-15-14-12 and 23-17-16-15-14-13, which are group 17 compounds in groups 17-16-15-14-1 through 17-16-15-14-13, (15) all of the compounds and/or groups described in group 18, (16) all of the compounds and/or groups described in group 19 and (17) all of the compounds and/or groups described in group 20.

Group 24. This group contains compounds in groups 1-20 above where R 4 substituents 1-10 listed in Table A are replaced with the following groups: 1 -thiophosphate or a salt, 2-phosphothioether, 3-thiophosphate thioether, 4 -phosphonoester, 5-phosphonate or a salt, 6-phosphonate ester, 7-phosphonate ether, 8-phosphonate thioether, 9 —O—S(O)(O)—OH or a -sulfate salt, e.g., —O—S(O)(O)—O + Na − , 10 —F, —Cl, —Br or —I.

Group 25. This group contains compounds in groups 1-20 above where R 4 substituents 1-10 listed in Table A are replaced with the following groups: 1-sulfate ester, 2-sulfate ether, 3-sulfate thioether, 4 —O—S(O)—OH, 5-sulfite salt, e.g., —O—S(O)—O + Na − , 6-sulfite ester, 7 -sulfite ether, 8-sulfoxide, 9 —O—S(O)(O)—OR PR and 10 —O—S(O)(O)—OCH 3 .

Exemplary sulfate esters include optionally substituted alkyl esters, e.g., methyl, ethyl, propyl or butyl ester, of 3β-hydroxyandrost-5-ene-17β-sulfate, 3α-hydroxyandrost-5-ene-17β-sulfate, 3β-hydroxy-16α-fluoroandrost-5-ene-17β-sulfate, 3α-hydroxy-16α-fluoroandrost-5-ene-17β-sulfate, 3β-hydroxy-5α-androstane-17β-sulfate, 3α-hydroxy-5α-androstane-17β-sulfate, 3β-hydroxy-5β-androstane-17β-sulfate, 3α-hydroxy-5β-androstane-17β-sulfate, 3β-hydroxy-5α, 14β-androstane-17β-sulfate, 3α-hydroxy-5α, 14β-androstane-17β-sulfate, 3β-hydroxy-5β, 14β-androstane-17β-sulfate, 3β-hydroxy-5β, 14β-androstane-17α-sulfate, or a salt, 2-oxa analog, 1α-alkyl, 10-alkyl, 4α-optionally substituted alkyl, 4β-optionally substituted alkyl, 7-substituted analog, 16α-halo, 16α-hydroxy, or 19-nor analog of any of these compounds.

Group 26. This group contains compounds in groups 1-20 above where R 4 substituents 1-10 listed in Table A are replaced with the following groups: 1-sulfonamide, 2-sulfonamide derivative, e.g., —S(O)(O)—NHR PR or —S(O)(O)—NH-optionally substituted alkyl, 3-sulfamate, 4-sulfamate derivative, e.g., —O—S(O)(O)—NHR PR , —O—S(O)(O)—N(RD) 2 or —O—S(O)(O)—NH-optionally substituted alkyl, 5-sulfonate, 6-sulfamide, 7-sulfinamide, 8-sulfurous diamide, 9-optionally protected monosaccharide, e.g., D-, L- or DL-glucose, galactose, fructose, rhamnose or glucuronic acid, 10-optionally protected oligosaccharide, e.g., D-, L- or DL-galactose-galactose, -galactose-mannose or -glucuronic acid-glucose. In this group, the optionally protected monosaccharide and optionally protected oligomonosaccharide moieties are typically linked to the 17-position through an oxygen, sulfur or nitrogen atom.

Exemplary group 26 compounds include glycosides such as 17β-glycosides and 17α-glycosides, 3β,16α-dihydroxyandrost-5-ene-17β-O-1′-β′-glucopyranose, 3α,16α-dihydroxyandrost-5-ene-17β-O-1′-β′-glucopyranose, 3α-hydroxy-16α-fluoroandrost-5-ene-17β-O-1′-β′-glucopyranose, 3β,16α-dihydroxyandrost-5-ene-17α-O-1′-β′-glucopyranose, 3α,16α-dihydroxyandrost-5-ene-17α-O-1′-β′-glucopyranose, 3α-hydroxy-16β-fluoroandrost-5-ene-17α-O-1′-β′-glucopyranose and analogs of any of these compounds having one, two or more moieties described herein for variable groups, e.g., 16α-halo, 16β-halo, 7α-hydroxy or thiol, 7β-hydroxy or thiol, 7-oxo, 7α-halo, 7β-halo, 7α-fluoro, 7β-fluoro, 7α-alkoxy, 7β-alkoxy, 4α-halo, 4β-halo, 4α-alkyl, 4β-alkyl, 12α-halo, 12β-halo, 12α-alkyl, 12β-alkyl, 11-dihalo, 11-alkyl, 11α-alkyl, 11-dialkyl, 2-oxa, 11-oxa, 15-oxa, 19-nor (i.e., R 6 is —H), 18-homo (i.e., R 5 is —C 2 H 5 ) or the like where any alkyl or alkoxy moieties are optionally substituted. Other exemplary moieties at R 4 include β-D-glucopyranosyl, β-D-glucopyranuronosyl, β-D-2-acetamido-2-deoxy-glucopyranosyl, β-D-galactopyranosyl, β-D-fucopyranosyl, β-L-fucopyranosyl, α-D-fructofuranosyl, β-D-fructofuranosyl, β-D-xylopyranosyl, β-L-xylopyranosyl, α-D-arabanopyranosyl, α-L-arabanopyranosyl, α-L-rhamnopyranosyl, α-D-rhamnopyranosyl, α-D-cellobiosyl, β-D-cellobiosyl, β-D-lactosyl, β-D-maltosyl, β-D-gentiobiosyl, 3-O-β-D-galactopyranosyl-α-D-arabanopyranosyl or β-D-maltotriosyl, any of which are optionally protected and where R 4 is in the α- or β-configuration.

These compounds include compounds in group 26-1 through 26-20-19-18-17-16-15-14-13, which collectively are group 26 compounds. These include groups 26-1, 26-2, 26-3, 26-4, 26-5, 26-5A, 26-6, 26-7, 26-8, 26-8A, 26-9, 26-10, 26-10A, 26-11, 26-12, 26-13, which are compounds in groups 1 through 13 where R 4 substituents 1-10 in Table A are replaced with the moieties given in this group. Group 26 compounds also include groups 26-14-1, 26-14-2, 26-14-3, 26-14-4, 26-14-5, 26-14-5A, 26-14-6, 26-14-7, 26-14-8, 26-14-8A, 26-14-9, 26-14-10, 26-14-10A, 26-14-11, 26-14-12 and 26-14-13, which are group 14 compounds in groups 14-1 through 14-13 where R 4 substituents 1-10 in Table A are replaced with the moieties given in this group.

Other group 26 compounds include (1) groups 26-15-1, 26-15-2, 26-15-3, 26-15-4, 26-15-5, 26-15-5A, 26-15-6, 26-15-7, 26-15-8, 26-15-8A, 26-15-9, 26-15-10, 26-15-10A, 26-15-11, 26-15-12 and 26-15-13, which are group 15 compounds in groups 15-1 through 15-13, (2) groups 26-16-1, 26-16-2, 26-16-3, 26-16-4, 26-16-5, 26-16-5A, 26-16-6, 26-16-7, 26-16-8, 26-16-8A, 26-16-9, 26-16-10, 26-16-10A, 26-16-11, 26-16-12 and 26-16-13, which are group 16 compounds in groups 16-1 through 16-13, (3) groups 26-17-1, 26-17-2, 26-17-3, 26-17-4, 26-17-5, 26-17-5A, 26-17-6, 26-17-7, 26-17-8, 26-17-8A, 26-17-9, 26-17-10, 26-17-10A, 26-17-11, 26-17-12 and 26-17-13, which are group 17 compounds in groups 17-1 through 17-13, (4) groups 26-15-14-1, 26-15-14-2, 26-15-14-3, 26-15-14-4, 26-15-14-5, 26-15-14-5A, 26-15-14-6, 26-15-14-7, 26-15-14-8, 26-15-14-8A, 26-15-14-9, 26-15-14-10, 26-15-14-10A, 26-15-14-11, 26-15-14-12 and 26-15-14-13, which are group 15 compounds in groups 15-14-1 through 15-14-13, (5) groups 26-16-14-1, 26-16-14-2, 26-16-14-3, 26-16-14-4, 26-16-14-5, 26-16-14-5A, 26-16-14-6, 26-16-14-7, 26-16-14-8, 26-16-14-8A, 26-16-14-9, 26-16-14-10, 26-16-14-10A, 26-16-14-11, 26-16-14-12 and 26-16-14-13, which are group 16 compounds in groups 16-14-1 through 16-14-13, (6) groups 26-17-14-1, 26-17-14-2, 26-17-14-3, 26-17-14-4, 26-17-14-5, 26-17-14-5A, 26-17-14-6, 26-17-14-7, 26-17-14-8, 26-17-14-8A, 26-17-14-9, 26-17-14-10, 26-17-14-10A, 26-17-14-11, 26-17-14-12, 26-17-14-13, which are group 17 compounds in groups 17-14-1 through 17-14-13, (7) groups 26-16-15-1, 26-16-15-2, 26-16-15-3, 26-16-15-4, 26-16-15-5, 26-16-15-5A, 26-16-15-6, 26-16-15-7, 26-16-15-8, 26-16-15-8A, 26-16-15-9, 26-16-15-10, 26-16-15-10A, 26-16-15-11, 26-16-15-12, 26-16-15-13, which are group 16 compounds in groups 16-15-1 through 16-15-13, (8) groups 26-17-15-1, 26-17-15-2, 26-17-15-3, 26-17-15-4, 26-17-15-5, 26-17-15-5A, 26-17-15-6, 26-17-15-7, 26-17-15-8, 26-17-15-8A, 26-17-15-9, 26-17-15-10, 26-17-15-10A, 26-17-15-11, 26-17-15-12, 26-17-15-13, which are group 17 compounds in groups 17-15-1 through 17-15-13, (9) groups 26-17-16-1, 26-17-16-2, 26-17-16-3, 26-17-16-4, 26-17-16-5, 26-17-16-5A, 26-17-16-6, 26-17-16-7, 26-17-16-8, 26-17-16-8A, 26-17-16-9, 26-17-16-10, 26-17-16-10A, 26-17-16-11, 26-17-16-12, 26-17-16-13, which are group 17 compounds in groups 17-16-1 through 17-16-13, (10) groups 26-16-15-14-1, 26-16-15-14-2, 26-16-15-14-3, 26-16-15-14-4, 26-16-15-14-5, 26-16-15-14-5A, 26-16-15-14-6, 26-16-15-14-7, 26-16-15-14-8, 26-16-15-14-8A, 26-16-15-14-9, 26-16-15-14-10, 26-16-15-14-10A, 26-16-15-14-11, 26-16-15-14-12, 26-16-15-14-13, which are group 16 compounds in groups 16-15-14-1 through 16-15-14-13, (11) groups 26-17-15-14-1, 26-17-15-14-2, 26-17-15-14-3, 26-17-15-14-4, 26-17-15-14-5, 26-17-15-14-5A, 26-17-15-14-6, 26-17-15-14-7, 26-17-15-14-8, 26-17-15-14-8A, 26-17-15-14-9, 26-17-15-14-10, 26-17-15-14-10A, 26-17-15-14-11, 26-17-15-14-12, 26-17-15-14-13, which are group 17 compounds in groups 17-15-14-1 through 17-15-14-13, (12) groups 26-17-16-14-1, 26-17-16-14-2, 26-17-16-14-3, 26-17-16-14-4, 26-17-16-14-5, 26-17-16-14-5A, 26-17-16-14-6, 26-17-16-14-7, 26-17-16-14-8, 26-17-16-14-8A, 26-17-16-14-9, 26-17-16-14-10, 26-17-16-14-10A, 26-17-16-14-11, 26-17-16-14-12, 26-17-16-14-13, which are group 17 compounds in groups 17-16-14-1 through 17-15-14-13, (13) groups 26-17-16-15-1, 26-17-16-15-2, 26-17-16-15-3, 26-17-16-15-4, 26-17-16-15-5, 26-17-16-15-5A, 26-17-16-15-6, 26-17-16-15-7, 26-17-16-15-8, 26-17-16-15-8A, 26-17-16-15-9, 26-17-16-15-10, 26-17-16-15-10A, 26-17-16-15-11, 26-17-16-15-12 and 26-17-16-15-13, which are group 17 compounds in groups 17-16-15-1 through 17-16-15-13, (14) groups 26-17-16-15-14-1, 26-17-16-15-14-2, 26-17-16-15-14-3, 26-17-16-15-14-4, 26-17-16-15-14-5, 26-17-16-15-14-5A, 26-17-16-15-14-6, 26-17-16-15-14-7, 26-17-16-15-14-8, 26-17-16-15-14-8A, 26-17-16-15-14-9, 26-17-16-15-14-10, 26-17-16-15-14-10A, 26-17-16-15-14-11, 26-17-16-15-14-12 and 26-17-16-15-14-13, which are group 17 compounds in groups 17-16-15-14-1 through 17-16-15-14-13, (15) all of the compounds and/or groups described in group 18, (16) all of the compounds and/or groups described in group 19 and (17) all of the compounds and/or groups described in group 20.

Group 26A. This group contains compounds in groups 1-20 above where R 4 substituents 1-10 listed in Table A are replaced with the following groups: 1 —N-pyrrolidine, 2 —N1-pyrazolone, 3 —N2-pyrazolone, 4 —N-imidazolidin-2-one, 5 —N1-imidazole, 6 —N1-4,5-dihydroimidazole, 7 —N-morpholine, 8 —N1-pyridine, 9 —N-piperidine, 10 —N-piperazine.

These compounds include compounds in group 26A-1 through 23-20-19-18-17-16-15-14-13, which collectively are group 26 compounds. These include groups 26A-1, 26A-2, 26A-3, 26A-4, 26A-5, 26A-5A, 26A-6, 26A-7, 26A-8, 26A-8A, 26-9, 26A-10, 26A-10A, 26A-11, 26A-12, 26A-13, which are compounds in groups 1 through 13 where R 4 substituents 1-10 in Table A are replaced with the moieties given in this group. Group 26A compounds also include groups 26A-14-1, 26A-14-2, 26A-14-3, 26A-14-4, 26A-14-5, 26A-14-5A, 26A-14-6, 26A-14-7, 26A-14-8, 26A-14-8A, 26A-14-9, 26A-14-10, 26A-14-10A, 26A-14-11, 26A-14-12 and 26A-14-13, which are group 14 compounds in groups 14-1 through 14-13 where R 4 substituents 1-10 in Table A are replaced with the moieties given in this group.

Other group 26A compounds include (1) groups 26A-15-1, 26A-15-2, 26A-15-3, 26A-15-4, 26A-15-5, 26A-15-5A, 26A-15-6, 26A-15-7, 26A-15-8, 26A-15-8A, 26A-15-9, 26A-15-10, 26A-15-10A, 26A-15-11, 26A-15-12 and 26A-15-13, which are group 15 compounds in groups 15-1 through 15-13, (2) groups 26A-16-1, 26A-16-2, 26A-16-3, 26A-16-4, 26A-16-5, 26A-16-5A, 26A-16-6, 26A-16-7, 26A-16-8, 26A-16-8A, 26A-16-9, 26A-16-10, 26A-16-10A, 26A-16-11, 26A-16-12 and 26A-16-13, which are group 16 compounds in groups 16-1 through 16-13, (3) groups 26A-17-1, 26A-17-2, 26A-17-3, 26A-17-4, 26A-17-5, 26A-17-5A, 26A-17-6, 26A-17-7, 26A-17-8, 26A-17-8A, 26A-17-9, 26A- 17-10, 26A-17-10A, 26A-17-11, 26A-17-12 and 26A-17-13, which are group 17 compounds in groups 17-1 through 17-13, (4) groups 26A-15-14-1, 26A-15-14-2, 26A-15-14-3, 26A-15-14-4, 26A-15-14-5, 26A-15-14-5A, 26A-15-14-6, 26A-15-14-7, 26A-15-14-8, 26A-15-14-8A, 26A-15-14-9, 26A-15-14-10, 26A-15-14-10A, 26A-15-14-11, 26A-15-14-12 and 26A-15-14-13, which are group 15 compounds in groups 15-14-1 through 15-14-13, (5) groups 26A-16-14-1, 26A-16-14-2, 26A-16-14-3, 26A-16-14-4, 26A-16-14-5, 26A-16-14-5A, 26A-16-14-6, 26A-16-14-7, 26A-16-14-8, 26A-16-14-8A, 26A-16-14-9, 26A-16-14-10, 26A-16-14-10A, 26A-16-14-11, 26A-16-14-12 and 26A-16-14-13, which are group 16 compounds in groups 16-14-1 through 16-14-13, (6) groups 26A-17-14-1, 26A-17-14-2, 26A-17-14-3, 26A-17-14-4, 26A-17-14-5, 26A-17-14-5A, 26A-17-14-6, 26A-17-14-7, 26A-17-14-8, 26A-17-14-8A, 26A-17-14-9, 26A-17-14-10, 26A-17-14-10A, 26A-17-14-11, 26A-17-14-12, 26A-17-14-13, which are group 17 compounds in groups 17-14-1 through 17-14-13, (7) groups 26A-16-15-1, 26A-16-15-2, 26A-16-15-3, 26A-16-15-4, 26A-16-15-5, 26A-16-15-5A, 26A-16-15-6, 26A-16-15-7, 26A-16-15-8, 26A-16-15-8A, 26A-16-15-9, 26A-16-15-10, 26A-16-15-10A, 26A-16-15-11, 26A-16-15-12, 26A-16-15-13, which are group 16 compounds in groups 16-15-1 through 16-15-13, (8) groups 26A-17-15-1, 26A-17-15-2, 26A-17-15-3, 26A-17-15-4, 26A-17-15-5, 26A-17-15-5A, 26A-17-15-6, 26A-17-15-7, 26A-17-15-8, 26A-17-15-8A, 26A-17-15-9, 26A-17-15-10, 26A-17-15-10A, 26A-17-15-11, 26A-17-15-12, 26A-17-15-13, which are group 17 compounds in groups 17-15-1 through 17-15-13, (9) groups 26A-17-16-1, 26A-17-16-2, 26A-17-16-3, 26A-17-16-4, 26A-17-16-5, 26A-17-16-5A, 26A-17-16-6, 26A-17-16-7, 26A-17-16-8, 26A-17-16-8A, 26A-17-16-9, 26A-17-16-10, 26A-17-16-10A, 26A-17-16-11, 26A-17-16-12, 26A-17-16-13, which are group 17 compounds in groups 17-16-1 through 17-16-13, (10) groups 26A-16-15-14-1, 26A-16-15-14-2, 26A-16-15-14-3, 26A-16-15-14-4, 26A-16-15-14-5, 26A-16-15-14-5A, 26A-16-15-14-6, 26A-16-15-14-7, 26A-16-15-14-8, 26A-16-15-14-8A, 26A-16-15-14-9, 26A-16-15-14-10, 26A-16-15-14-10A, 26A-16-15-14-11, 26A-16-15-14-12, 26A-16-15-14-13, which are group 16 compounds in groups 16-15-14-1 through 16-15-14-13, (11) groups 26A-17-15-14-1, 26A-17-15-14-2, 26A-17-15-14-3, 26A-17-15-14-4, 26A-17-15-14-5, 26A-17-15-14-5A, 26A-17-15-14-6, 26A-17-15-14-7, 26A-17-15-14-8, 26A-17-15-14-8A, 26A-17-15-14-9, 26A-17-15-14-10, 26A-17-15-14-10A, 26A-17-15-14-11, 26A-17-15-14-12, 26A-17-15-14-13, which are group 17 compounds in groups 17-15-14-1 through 17-15-14-13, (12) groups 26A-17-16-14-1, 26A-17-16-14-2, 26A-17-16-14-3, 26A-17-16-14-4, 26A-17-16-14-5, 26A-17-16-14-5A, 26A-17-16-14-6, 26A-17-16-14-7, 26A-17-16-14-8, 26A-17-16-14-8A, 26A-17-16-14-9, 26A-17-16-14-10, 26A-17-16-14-10A, 26A-17-16-14-11, 26A-17-16-14-12, 26A-17-16-14-13, which are group 17 compounds in groups 17-16-14-1 through 17-15-14-13, (13) groups 26A-17-16-15-1, 26A-17-16-15-2, 26A-17-16-15-3, 26A-17-16-15-4, 26A-17-16-15-5, 26A-17-16-15-5A, 26A-17-16-15-6, 26A-17-16-15-7, 26A-17-16-15-8, 26A-17-16-15-8A, 26A-17-16-15-9, 26A-17-16-15-10, 26A-17-16-15-10A, 26A-17-16-15-11, 26A-17-16-15-12 and 26A-17-16-15-13, which are group 17 compounds in groups 17-16-15-1 through 17-16-15-13, (14) groups 26A-17-16-15-14-1, 26A-17-16-15-14-2, 26A-17-16-15-14-3, 26A-17-16-15-14-4, 26A-17-16-15-14-5, 26A-17-16-15-14-5A, 26A-17-16-15-14-6, 26A-17-16-15-14-7, 26A-17-16-15-14-8, 26A-17-16-15-14-8A, 26A-17-16-15-14-9, 26A-17-16-15-14-10, 26A-17-16-15-14-10A, 26A-17-16-15-14-11, 26A-17-16-15-14-12 and 26A-17-16-15-14-13, which are group 17 compounds in groups 17-16-15-14-1 through 17-16-15-14-13, (15) all of the compounds and/or groups described in group 18, (16) all of the compounds and/or groups described in group 19 and (17) all of the compounds and/or groups described in group 20.

Group 26B. This group contains compounds in groups 1-20 above where R 4 substituents 1-10 listed in Table A are replaced with the following groups: 1 —N-piperazine substituted at N4 with optionally substituted alkyl, 2 —N-indole, 3 —N-indoline, 4 —N-quinolidine, 5 —NH—C(O)—CH 2 —CH 2 —C(O)—OH, 6 —NH—C(O)—CH 2 —C(O)—OH, 7 —NH—C(O)—CH 2 —CH 2 —C(O)—OR PR , 8 —NH—C(O)—CH 2 —C(O)—OR PR , 9 —NH—C(O)—(CH 2 ) 3 —C(O)—OH, 10 —NH—C(O)—(CH 2 ) 3 —C(O)—OR PR . Ionizable moieties such as free carboxyl groups include salts, e.g., Na + or K + . R PR is a protecting group.

Group 26C. This group contains compounds in groups 1-20 above where R 4 substituents 1-10 listed in Table A are replaced with the following groups: 1 —NH—CH(CH 3 )—C(O)OH, 2 —NH—CH(CH 3 )—C(O)OR PR , 3 —NH—CH(CH 2 OH)—C(O)OH, 4 —NH—CH(CH 2 OH)—C(O)OR PR , 5 —NH—CH 2 —CH 2 —C(O)—OH, 6 —NH—CH 2 —C(O)—OH, 7 —NH—CH 2 —CH 2 —C(O)—OR PR , 8 —NH—CH 2 —C(O)—OR PR , 9 —NH—(CH 2 ) 3 —C(O)—OH, 10 —NH—(CH 2 ) 3 —C(O)—OR PR . Ionizable moieties such as free carboxyl groups include salts, e.g., Na + or K + . R PR is a protecting group.

Group 26D. This group contains compounds in groups 1-20 above where R 4 substituents 1-10 listed in Table A are replaced with the following groups: 1 —NH—CH(CH 3 )—C(O)OH, 2 —NH—NH—C(O)CH 3 , 3 —NH—NH—C(O)OCH 3 , 4 —NH—NH—C(O)C 2 H 5 , 5 —NH—NH—C(O)OC 2 H 5 , 6 —NH—NH—C(O)C 3 H 7 , 7 —NH—NH—C(O)-optionally substituted alkyl, 8 —NH—C(NH-optionally substituted alkyl)=N-optionally substituted alkyl, 9 —NH—C(NH—CH 3 )═N—CH 3 , 10 —NH—C(NH—C 2 H 5 )═N—C 2 H 5 .

Group 26E. This group contains compounds in groups 1-20 above where R 4 substituents 1-10 listed in Table A are replaced with the following groups: 1 spiro β-NH—(CH 2 ) 2 —O-α, 2 spiro α-NH—(CH 2 ) 2 —O-β, 3 spiro β-NH—(CH 2 ) 2 —NH-α, 4 spiro α-NH—(CH 2 ) 2 —NH-β, 5 spiro β-NH—CH═N—CH 2 -α, 6 spiro α-NH—CH═N—CH 2 -β, 7 spiro β-NH—CHR 10 —CHR 10 —O-α, 8 spiro α-NH—CHR 10 —CHR 10 —O-β, 9 spiro β-NH—CHR 10 —CHR 10 —NH-α, 10 spiro α-NH—CHR 10 —CHR 10 —NH-β. Each R 10 is independently chosen and has the meaning given above, e.g., —H, —OH, ═O, —SH, ═S, halogen or optionally substituted alkyl.

Group 27. This group contains compounds in groups 1-20 above where R 4 substituents 1-10 listed in Table A are replaced with the following groups: 1-glycol, e.g., propylene glycol or ethylene glycol, 2-polyethylene glycol, e.g., PEG 100 or PEG 200, 3-an acetal ring, 4-a spiro ring, 5-a thioacetal ring, 6 spiro —O—CH 2 —O—, 7 spiro —O—(CH 2 ) 2 —O—, 8 spiro —NH—(CH 2 ) 2 —O—, 9 —NH—C(O)—(CH 2 ) 2 —C(O)O—CH 3 , 10 —NH—C(O)—(CH 2 ) 2 —C(O)—OH.

Group 28. This group contains compounds in groups 1-27 above where R 1 substituents 1-10 listed in Table A are replaced with the following groups: 1-optionally substituted amine, 2-optionally substituted amide, 3-optionally substituted oxime, 4-optionally substituted alkyl, 5-optionally substituted alkenyl, 6-optionally substituted alkynyl, 7-optionally substituted aryl, 8-optionally substituted heterocycle, 9-ether and 10-ester. Any of these groups can be a moiety defined herein for that group. Thus, for Table A substituent 1, optionally substituted amine, the R 1 group includes moieties such as —NH 2 , —NH 3 + Cl − , —NH 3 + Br − , —NH 3 + I − , optionally substituted alkylamine, di-optionally substituted alkylamine, —NH—CH 3 , —N(CH 3 ) 2 , —N(C 2 H 5 ) 2 , —N(n-propyl) 2 , —N(i-propyl) 2 , —N(n-butyl) 2 , —N(t-butyl) 2 , —NH—C 1-4 alkyl, —NH—C 1-4 hydroxyalkyl, —NH—C 1-4 fluoroalkyl, —NH—CH 2 —CH 2 —O—CH 3 , —NH-optionally substituted alkyl, —N(optionally substituted alkyl) 2 , —NH—C 6 H 5 , —N(C 6 H 5 ) 2 , —NH-optionally substituted monosaccharide and —NH-optionally substituted oligosaccharide, and optionally substituted amide includes —NHC(O)-optionally substituted alkyl, —N(CH 3 )—C(O)-optionally substituted alkyl, —N(C 2 H 5 )—C(O)-optionally substituted alkyl, —N(C 3 H 7 )—C(O)-optionally substituted alkyl, —N(C 4 H 9 )—C(O)-optionally substituted alkyl, —N(C 6 H 5 )—C(O)-optionally substituted alkyl, —NH—C(O)-optionally substituted monosaccharide and —NH—C(O)-optionally substituted oligosaccharide, where alkyl or phenyl groups are the same or different and are optionally substituted as described herein.

These compounds include compounds in group 28-1 through 28-27-20-19-18-17-16-15-14-13, which collectively are group 28 compounds. These include groups 28-1, 28-2, 28-3, 28-4, 28-5, 28-5A, 28-6, 28-7, 28-8, 28-8A, 28-9, 28-10, 28-10A, 28-11, 28-12, 28-13, which are compounds in groups 1 through 13 where R 1 substituents 1-10 in Table A are replaced with the moieties given in this group. Group 28 compounds also include groups 28-14-1, 28-14-2, 28-14-3, 28-14-4, 28-14-5, 28-14-5A, 28-14-6, 28-14-7, 28-14-8, 28-14-8A, 28-14-9, 28-14-10, 28-14-10A, 28-14-11, 28-14-12 and 28-14-13, which are group 14 compounds in groups 14-1 through 14-13 where R 1 substituents 1-10 in Table A are replaced with the moieties given in this group.

Other group 28 compounds include (1) groups 28-15-1, 28-15-2, 28-15-3, 28-15-4, 28-15-5, 28-15-5A, 28-15-6, 28-15-7, 28-15-8, 28-15-8A, 28-15-9, 28-15-10, 28-15-10A, 28-15-11, 28-15-12 and 28-15-13, which are group 15 compounds in groups 15-1 through 15-13, (2) groups 28-16-1, 28-16-2, 28-16-3, 28-16-4, 28-16-5, 28-16-5A, 28-16-6, 28-16-7, 28-16-8, 28-16-8A, 28-16-9, 28-16-10, 28-16-10A, 28-16-11, 28-16-12 and 28-16-13, which are group 16 compounds in groups 16-1 through 16-13, (3) groups 28-17-1, 28-17-2, 28-17-3, 28-17-4, 28-17-5, 28-17-5A, 28-17-6, 28-17-7, 28-17-8, 28-17-8A, 28-17-9, 28-17-10, 28-17-10A, 28-17-11, 28-17-12 and 28-17-13, which are group 17 compounds in groups 17-1 through 17-13, (4) groups 28-15-14-1, 28-15-14-2, 28-15-14-3, 28-15-14-4, 28-15-14-5, 28-15-14-5A, 28-15-14-6, 28-15-14-7, 28-15-14-8, 28-15-14-8A, 28-15-14-9, 28-15-14-10, 28-15-14-10A, 28-15-14-11, 28-15-14-12 and 28-15-14-13, which are group 15 compounds in groups 15-14-1 through 15-14-13, (5) groups 28-16-14-1, 28-16-14-2, 28-16-14-3, 28-16-14-4, 28-16-14-5, 28-16-14-5A, 28-16-14-6, 28-16-14-7, 28-16-14-8, 28-16-14-8A, 28-16-14-9, 28-16-14-10, 28-16-14-10A, 28-16-14-11, 28-16-14-12 and 28-16-14-13, which are group 16 compounds in groups 16-14-1 through 16-14-13, (6) groups 28-17-14-1, 28-17-14-2, 28-17-14-3, 28-17-14-4, 28-17-14-5, 28-17-14-5A, 28-17-14-6, 28-17-14-7, 28-17-14-8, 28-17-14-8A, 28-17-14-9, 28-17-14-10, 28-17-14-10A, 28-17-14-11, 28-17-14-12, 28-17-14-13, which are group 17 compounds in groups 17-14-1 through 17-14-13, (7) groups 28-16-15-1, 28-16-15-2, 28-16-15-3, 28-16-15-4, 28-16-15-5, 28-16-15-5A, 28-16-15-6, 28-16-15-7, 28-16-15-8, 28-16-15-8A, 28-16-15-9, 28-16-15-10, 28-16-15-10A, 28-16-15-11, 28-16-15-12, 28-16-15-13, which are group 16 compounds in groups 16-15-1 through 16-15-13, (8) groups 28-17-15-1, 28-17-15-2, 28-17-15-3, 28-17-15-4, 28-17-15-5, 28-17-15-5A, 28-17-15-6, 28-17-15-7, 28-17-15-8, 28-17-15-8A, 28-17-15-9, 28-17-15-10, 28-17-15-10A, 28-17-15-11, 28-17-15-12, 28-17-15-13, which are group 17 compounds in groups 17-15-1 through 17-15-13, (9) groups 28-17-16-1, 28-17-16-2, 28-17-16-3, 28-17-16-4, 28-17-16-5, 28-17-16-5A, 28-17-16-6, 28-17-16-7, 28-17-16-8, 28-17-16-8A, 28-17-16-9, 28-17-16-10, 28-17-16-10A, 28-17-16-11, 28-17-16-12, 28-17-16-13, which are group 17 compounds in groups 17-16-1 through 17-16-13, (10) groups 28-16-15-14-1, 28-16-15-14-2, 28-16-15-14-3, 28-16-15-14-4, 28-16-15-14-5, 28-16-15-14-5A, 28-16-15-14-6, 28-16-15-14-7, 28-16-15-14-8, 28-16-15-14-8A, 28-16-15-14-9, 28-16-15-14-10, 28-16-15-14-10A, 28-16-15-14-11, 28-16-15-14-12, 28-16-15-14-13, which are group 16 compounds in groups 16-15-14-1 through 16-15-14-13, (11) groups 28-17-15-14-1, 28-17-15-14-2, 28-17-15-14-3, 28-17-15-14-4, 28-17-15-14-5, 28-17-15-14-5A, 28-17-15-14-6, 28-17-15-14-7, 28-17-15-14-8, 28-17-15-14-8A, 28-17-15-14-9, 28-17-15-14-10, 28-17-15-14-10A, 28-17-15-14-11, 28-17-15-14-12, 28-17-15-14-13, which are group 17 compounds in groups 17-15-14-1 through 17-15-14-13, (12) groups 28-17-16-14-1, 28-17-16-14-2, 28-17-16-14-3, 28-17-16-14-4, 28-17-16-14-5, 28-17-16-14-5A, 28-17-16-14-6, 28-17-16-14-7, 28-17-16-14-8, 28-17-16-14-8A, 28-17-16-14-9, 28-17-16-14-10, 28-17-16-14-10A, 28-17-16-14-11, 28-17-16-14-12, 28-17-16-14-13, which are group 17 compounds in groups 17-16-14-1 through 17-15-14-13, (13) groups 28-17-16-15-1, 28-17-16-15-2, 28-17-16-15-3, 28-17-16-15-4, 28-17-16-15-5, 28-17-16-15-5A, 28-17-16-15-6, 28-17-16-15-7, 28-17-16-15-8, 28-17-16-15-8A, 28-17-16-15-9, 28-17-16-15-10, 28-17-16-15-10A, 28-17-16-15-11, 28-17-16-15-12 and 28-17-16-15-13, which are group 17 compounds in groups 17-16-15-1 through 17-16-15-13, (14) groups 28-17-16-15-14-1, 28-17-16-15-14-2, 28-17-16-15-14-3, 28-17-16-15-14-4, 28-17-16-15-14-5, 28-17-16-15-14-5A, 28-17-16-15-14-6, 28-17-16-15-14-7, 28-17-16-15-14-8, 28-17-16-15-14-8A, 28-17-16-15-14-9, 28-17-16-15-14-10, 28-17-16-15-14-10A, 28-17-16-15-14-11, 28-17-16-15-14-12 and 28-17-16-15-14-13, which are group 17 compounds in groups 17-16-15-14-1 through 17-16-15-14-13, (15) all of the compounds and/or groups described in group 18, (16) all of the compounds and/or groups described in group 19, (17) all of the compounds and/or groups described in group 20, and (18) all of the compounds and/or groups described in groups 21, 22, 23, 24, 25, 26, 26A, 26B, 26C, 26E and 27.

Group 29. This group contains compounds in groups 1-27 above where R 1 substituents 1-10 listed in Table A are replaced with the following groups: 1-acyl, 2-thioester, 3-thioether, 4-thioacyl, 5-epoxide, 6-optionally substituted cyclopropyl, 7 —O—Si(C1-C6 alkyl) 3 , 8-phosphate or a salt, e.g., Na + or K + , 9-phosphate ester or a salt, e.g., Na + or K + , and 10-phosphate ether or a salt, e.g., Na + or K + . Any of these groups can be a moiety defined herein for that group. Thus, for Table A substituent 1, acyl, the R 1 group includes moieties such as —C(O)CH 3 , —C(O)C 2 H 5 , —C(O)CH 2 OH, —C(O)CH 2 -halogen and —C(O)-optionally substituted alkyl. Similarly, thioester includes moieties such as —C(O)—SCH 3 , —S—C(O)-optionally substituted alkyl and —C(O)—S-optionally substituted alkyl. The epoxide and optionally substituted cyclopropyl moieties for substituents 5 and 6 respectively can be at the 2-3 positions or at the 3-4 positions in the α- or β-configuration.

Exemplary phosphate and phosphate esters include 17β-hydroxyandrost-5-ene-3β-phosphate, 17β-hydroxyandrost-5-ene-3α-phosphate, 17β-hydroxy-16α-fluoroandrost-5-ene-3β-phosphate, 17β-hydroxy-16α-fluoroandrost-5-ene-3α-phosphate, 17β-hydroxy-5α-androstane-3β-phosphate, 17β-hydroxy-5α-androstane-3α-phosphate, 17β-hydroxy-5β-androstane-3β-phosphate, 17β-hydroxy-5β-androstane-3α-phosphate, 17β-hydroxy-5α, 14β-androstane-3β-phosphate, 17β-hydroxy-5α, 14β-androstane-3α-phosphate, 17β-hydroxy-5β, 14β-androstane-3β-phosphate, 17α-hydroxy-5β, 14β-androstane-3β-phosphate, or a salt, 2-oxa analog, 1α-alkyl, 4α-optionally substituted alkyl, 7-substituted analog, 16α-halo, 16α-hydroxy, 19-nor analog or phosphate ester, e.g., phosphate methyl ester (—O—P(O)(O)—OCH 3 ), phosphate ethyl ester or phosphate optionally substituted alkyl ester of any of these compounds.

Group 30. This group contains compounds in groups 1-27 above where R 1 substituents 1-10 listed in Table A are replaced with the following groups: 1-phosphate thioether, 2-thionoester, 3-amino acid, 4-peptide, 5-dipeptide, 6-optionally substituted heterocycle, 7-optionally substituted carboxyl, 8-carbonate, 9-carbamate and 10-phosphothioester. Exemplary carbamate moieties are as described herein, e.g., —NH—C(O)—O—CH 3 , —NH—C(O)—O—C 2 H 5 , —NH—C(O)—O—C 3 H 7 , —NH—C(O)—O—C 3 H 5 , —NH—C(O)—O—C 4 H 9 , —NH—C(O)—O-optionally substituted alkyl, —NH—C(O)—O-optionally substituted heterocycle and —NH—C(O)—O-optionally substituted monosaccharide. Exemplary ester moieties are as described herein, e.g., —O—C(O)—CH 3 , —O—C(O)—CF 3 , —O—C(O)—C 2 H 5 , —O——C(O)—C 3 H 7 , and —O—C(O)—C 4 H 9 . Exemplary optionally substituted carboxyl moieties are described herein, including —C(O)OH or a salt, —C(O)—OCH 3 , —C(O)—OC 2 H 5 and —C(O)—OC 3 H 7 . Exemplary group 30 compounds include 17β-hydroxyandrost-5-ene-3β-carbamate, 17β-hydroxyandrost-1,5-diene-3β-carbamate, 17β-hydroxyandrost-5-ene-3α-carbamate, 17α-hydroxyandrost-5-ene-3β-carbamate, 17α-hydroxyandrost-5-ene-3α-carbamate, 17β-hydroxyandrost-4-ene-3β-carbamate, 17α-hydroxyandrost-4-ene-3β-carbamate, 17α-hydroxyandrost-1,4-diene-3β-carbamate, 17β-hydroxyandrost-1,5,16-triene-3-carbamate, and analogs of any of these compounds having one, two or more moieties such as 16α-halo, 16α-fluoro, 16β-fluoro, 16-fluoro, 16α-hydroxy, 7α-hydroxy or thiol, 7β-hydroxy or thiol, 7-oxo, 7α-halo, 7β-halo, 7α-fluoro, 7β-fluoro, 7α-alkoxy, 7β-alkoxy, 4α-halo, 4β-halo, 4α-alkyl, 4β-alkyl, 12α-halo, 12β-halo, 12α-alkyl, 12β-alkyl, 11-dihalo, 11-dialkyl, 2-oxa, 11-oxa, 17-oxo, 19-nor or the like. Other moieties, e.g., amino acid and optionally substituted heterocycle, are as described herein.

Group 31. This group contains compounds in groups 1-27 above where R 1 substituents 1-10 listed in Table A are replaced with the following groups: 1 -thiophosphate, 2-phosphothioether, 3-thiophosphate thioether, 4-phosphonoester, 5 -phosphonate, 6-phosphonate ester, 7-phosphonate ether, 8-phosphonate thioether, 9 —O—S(O)(O)—OH and 10-sulfate salt, e.g., —O—S(O)(O)—O + Na − .

Group 32. This group contains compounds in groups 1-27 above where R 1 substituents 1-10 listed in Table A are replaced with the following groups: 1-sulfate ester, e.g., —O—S(O)(O)—O—CH 3 and —O—S(O)(O)—O—C 2 H 5 , 2-sulfate ether, 3-sulfate thioether, 4 —O—S(O)—OH, 5-sulfite salt, e.g., —O—S(O)—O + Na − , 6-sulfite ester, 7-sulfite ether, 8 -sulfoxide, 9 —O—S(O)(O)—OH or a sulfate salt, e.g., —O—S(O)(O)—O + Na − , 10 —F, —Cl, —Br or —I.

Group 33. This group contains compounds in groups 1-27 above where R 1 substituents 1-10 listed in Table A are replaced with the following groups: 1-sulfonamide, 2-sulfonamide derivative, e.g., —S(O)(O)—NHR PR or —S(O)(O)—NH-optionally substituted alkyl, 3-sulfamate, 4-sulfamate derivative, e.g., —O—S(O)(O)—NHR PR , —O—S(O)(O)—NHCH 3 , —O—S(O)(O)—NHC 2 H 5 , —O—S(O)(O)—NHC 3 H 7 , —O—S(O)(O)—NHC 4 H 9 , —O—S(O)(O)—N(RD) 2 or —O—S(O)(O)—NH-optionally substituted alkyl, 5-sulfonate, 6-sulfamide, 7-sulfinamide, 8 -sulfurous diamide, 9-optionally protected monosaccharide, e.g., D-, L- or DL-glucose, fructose, rhamnose or glucuronic acid, 10-optionally protected oligosaccharide, e.g., D-, L- or DL-galactose-galactose, -galactose-mannose or -glucuronic acid-glucose. In this group, the optionally protected monosaccharide and optionally protected oligomonosaccharide moieties are typically linked to the 3-position through an oxygen, sulfur or nitrogen atom.

Exemplary group 33 compounds include glycosides such as 3β-glycosides and 3α-glycosides, 17β, 16α-dihydroxyandrost-5-ene-3β-O-1′-β′-glucopyranose, 17α, 16α-dihydroxyandrost-5-ene-3β-O-1′-β′-glucopyranose, 17β-hydroxy-16α-fluoroandrost-5-ene-3β-O-1′-β′-glucopyranose, 17β,16α-dihydroxyandrost-5-ene-3α-O-1′-β′-glucopyranose, 17α, 16α-dihydroxyandrost-5-ene-3α-O-1′-β′-glucopyranose, 17α-hydroxy-16β-fluoroandrost-5-ene-3α-O-1′-β′-glucopyranose and analogs of any of these compounds having one, two or more moieties described herein for variable groups, e.g., 16α-halo, 16β-halo, 7α-hydroxy or thiol, 7β-hydroxy or thiol, 7-oxo, 7α-halo, 7β-halo, 7α-fluoro, 7β-fluoro, 7α-alkoxy, 7β-alkoxy, 4α-halo, 4β-halo, 4α-alkyl, 4β-alkyl, 12α-halo, 12β-halo, 12α-alkyl, 12β-alkyl, 11-dihalo, 11-alkyl, 11α-alkyl, 11-dialkyl, 2-oxa, 11-oxa, 15-oxa, 17-oxo 19-nor (i.e., R 6 is —H), 18-homo (i.e., R 5 is —C 2 H 5 ) or the like where any alkyl or alkoxy moieties are optionally substituted. Other exemplary moieties at R 1 include β-D-glucopyranosyl, β-D-glucopyranuronosyl, β-D-2-acetamido-2-deoxy-glucopyranosyl, β-D-galactopyranosyl, β-D-fucopyranosyl, β-L-fucopyranosyl, α-D-fructofuranosyl, β-D-fructofuranosyl, β-D-xylopyranosyl, β-L-xylopyranosyl, α-D-arabanopyranosyl, α-L-arabanopyranosyl, α-L-rhamnopyranosyl, α-D-rhamnopyranosyl, α-D-cellobiosyl, β-D-cellobiosyl, β-D-lactosyl, β-D-maltosyl, β-D-gentiobiosyl, 3-O-β-D-galactopyranosyl-α-D-arabanopyranosyl and β-D-maltotriosyl moieties, any of which are optionally protected and where R 1 is in the α- or β-configuration.

These compounds include compounds in group 33-1 through 33-27-20-19-18-17-16-15-14-13, which collectively are group 33 compounds. These include groups 33-1, 33-2, 33-3, 33-4, 33-5, 33-5A, 33-6, 33-7, 33-8, 33-8A, 33-9, 33-10, 33-10A, 33-11, 33-12, 33-13, which are compounds in groups 1 through 13 where R 1 substituents 1-10 in Table A are replaced with the moieties given in this group. Group 33 compounds also include groups 33-14-1, 33-14-2, 33-14-3, 33-14-4, 33-14-5, 33-14-5A, 33-14-6, 33-14-7, 33-14-8, 33-14-8A, 33-14-9, 33-14-10, 33-14-10A, 33-14-11, 33-14-12 and 33-14-13, which are group 14 compounds in groups 14-1 through 14-13 where R 1 substituents 1-10 in Table A are replaced with the moieties given in this group.

Other group 33 compounds include (1) groups 33-15-1, 33-15-2, 33-15-3, 33-15-4, 33-15-5, 33-15-5A, 33-15-6, 33-15-7, 33-15-8, 33-15-8A, 33-15-9, 33-15-10, 33-15-10A, 33-15-11, 33-15-12 and 33-15-13, which are group 15 compounds in groups 15-1 through 15-13, (2) groups 33-16-1, 33-16-2, 33-16-3, 33-16-4, 33-16-5, 33-16-5A, 33-16-6, 33-16-7, 33-16-8, 33-16-8A, 33-16-9, 33-16-10, 33-16-10A, 33-16-11, 33-16-12 and 33-16-13, which are group 16 compounds in groups 16-1 through 16-13, (3) groups 33-17-1, 33-17-2, 33-17-3, 33-17-4, 33-17-5, 33-17-5A, 33-17-6, 33-17-7, 33-17-8, 33-17-8A, 33-17-9, 33-17-10, 33-17-10A, 33-17-11, 33-17-12 and 33-17-13, which are group 17 compounds in groups 17-1 through 17-13, (4) groups 33-15-14-1, 33-15-14-2, 33-15-14-3, 33-15-14-4, 33-15-14-5, 33-15-14-5A, 33-15-14-6, 33-15-14-7, 33-15-14-8, 33-15-14-8A, 33-15-14-9, 33-15-14-10, 33-15-14-10A, 33-15-14-11, 33-15-14-12 and 33-15-14-13, which are group 15 compounds in groups 15-14-1 through 15-14-13, (5) groups 33-16-14-1, 33-16-14-2, 33-16-14-3, 33-16-14-4, 33-16-14-5, 33-16-14-5A, 33-16-14-6, 33-16-14-7, 33-16-14-8, 33-16-14-8A, 33-16-14-9, 33-16-14-10, 33-16-14-10A, 33-16-14-11, 33-16-14-12 and 33-16-14-13, which are group 16 compounds in groups 16-14-1 through 16-14-13, (6) groups 33-17-14-1, 33-17-14-2, 33-17-14-3, 33-17-14-4, 33-17-14-5, 33-17-14-5A, 33-17-14-6, 33-17-14-7, 33-17-14-8, 33-17-14-8A, 33-17-14-9, 33-17-14-10, 33-17-14-10A, 33-17-14-11, 33-17-14-12, 33-17-14-13, which are group 17 compounds in groups 17-14-1 through 17-14-13, (7) groups 33-16-15-1, 33-16-15-2, 33-16-15-3, 33-16-15-4, 33-16-15-5, 33-16-15-5A, 33-16-15-6, 33-16-15-7, 33-16-15-8, 33-16-15-8A, 33-16-15-9, 33-16-15-10, 33-16-15-10A, 33-16-15-11, 33-16-15-12, 33-16-15-13, which are group 16 compounds in groups 16-15-1 through 16-15-13, (8) groups 33-17-15-1, 33-17-15-2, 33-17-15-3, 33-17-15-4, 33-17-15-5, 33-17-15-5A, 33-17-15-6, 33-17-15-7, 33-17-15-8, 33-17-15-8A, 33-17-15-9, 33-17-15-10, 33-17-15-10A, 33-17-15-11, 33-17-15-12, 33-17-15-13, which are group 17 compounds in groups 17-15-1 through 17-15-13, (9) groups 33-17-16-1, 33-17-16-2, 33-17-16-3, 33-17-16-4, 33-17-16-5, 33-17-16-5A, 33-17-16-6, 33-17-16-7, 33-17-16-8, 33-17-16-8A, 33-17-16-9, 33-17-16-10, 33-17-16-10A, 33-17-16-11, 33-17-16-12, 33-17-16-13, which are group 17 compounds in groups 17-16-1 through 17-16-13, (10) groups 33-16-15-14-1, 33-16-15-14-2, 33-16-15-14-3, 33-16-15-14-4, 33-16-15-14-5, 33-16-15-14-5A, 33-16-15-14-6, 33-16-15-14-7, 33-16-15-14-8, 33-16-15-14-8A, 33-16-15-14-9, 33-16-15-14-10, 33-16-15-14-10A, 33-16-15-14-11, 33-16-15-14-12, 33-16-15-14-13, which are group 16 compounds in groups 16-15-14-1 through 16-15-14-13, (11) groups 33-17-15-14-1, 33-17-15-14-2, 33-17-15-14-3, 33-17-15-14-4, 33-17-15-14-5, 33-17-15-14-5A, 33-17-15-14-6, 33-17-15-14-7, 33-17-15-14-8, 33-17-15-14-8A, 33-17-15-14-9, 33-17-15-14-10, 33-17-15-14-10A, 33-17-15-14-11, 33-17-15-14-12, 33-17-15-14-13, which are group 17 compounds in groups 17-15-14-1 through 17-15-14-13, (12) groups 33-17-16-14-1, 33-17-16-14-2, 33-17-16-14-3, 33-17-16-14-4, 33-17-16-14-5, 33-17-16-14-5A, 33-17-16-14-6, 33-17-16-14-7, 33-17-16-14-8, 33-17-16-14-8A, 33-17-16-14-9, 33-17-16-14-10, 33-17-16-14-10A, 33-17-16-14-11, 33-17-16-14-12, 33-17-16-14-13, which are group 17 compounds in groups 17-16-14-1 through 17-15-14-13, (13) groups 33-17-16-15-1, 33-17-16-15-2, 33-17-16-15-3, 33-17-16-15-4, 33-17-16-15-5, 33-17-16-15-5A, 33-17-16-15-6, 33-17-16-15-7, 33-17-16-15-8, 33-17-16-15-8A, 33-17-16-15-9, 33-17-16-15-10, 33-17-16-15-10A, 33-17-16-15-11, 33-17-16-15-12 and 33-17-16-15-13, which are group 17 compounds in groups 17-16-15-1 through 17-16-15-13, (14) groups 33-17-16-15-14-1, 33-17-16-15-14-2, 33-17-16-15-14-3, 33-17-16-15-14-4, 33-17-16-15-14-5, 33-17-16-15-14-5A, 33-17-16-15-14-6, 33-17-16-15-14-7, 33-17-16-15-14-8, 33-17-16-15-14-8A, 33-17-16-15-14-9, 33-17-16-15-14-10, 33-17-16-15-14-10A, 33-17-16-15-14-11, 33-17-16-15-14-12 and 33-17-16-15-14-13, which are group 17 compounds in groups 17-16-15-14-1 through 17-16-15-14-13, (15) all of the compounds and/or groups described in group 18, (16) all of the compounds and/or groups described in group 19, (17) all of the compounds and/or groups described in group 20, and (18) all of the compounds and/or groups described in groups 21, 22, 23, 24, 25, 26, 26A, 26B, 26C, 26E and 27.

Group 33A. This group contains compounds in groups 1-27 above where R 1 substituents 1-10 listed in Table A are replaced with the following groups: 1 —N-pyrrolidine, 2 —N1-pyrazolone, 3 —N2-pyrazolone, 4 —N-imidazolidin-2-one, 5 —N1-imidazole, 6 —N1-4,5-dihydroimidazole, 7 —N-morpholine, 8 —N1-pyridine, 9 —N-piperidine, 10 —N-piperazine. As examples, group 33A-3 compound 1.1.6.9 (i.e., group 33A compound 1.1.6.9 from group 3) is 3β-N-pyrrolidinyl-16α, 17β-dihydroxyandrost-5-ene and 33A-3 compound 1.1.4.9 is 3β-N-pyrrolidinyl-16α-fluoro-17β-hydroxyandrost-5-ene, group 33A-4 compound 1.1.6.9 (i.e., group 26A compound 1.1.6.9 from group 4) is 3β-N-pyrrolidinyl-16α, 17β-dihydroxyandrost-1,5-diene and 26A-4 compound 1.1.4.9 is 3β-N-pyrrolidinyl-16α-fluoro-17β-hydroxyandrost-1,5-diene.

These compounds include compounds in group 33A-1 through 33A-27-20-19-18-17-16-15-14-13, which collectively are group 33A compounds. These include groups 33A-1, 33A-2, 33A-3, 33A-4, 33A-5, 33A-5A, 33A-6, 33A-7, 33A-8, 33A-8A, 33A-9, 33A-10, 33A-10A, 33A-11, 33A-12, 33A-13, which are compounds in groups 1 through 13 where R 1 substituents 1-10 in Table A are replaced with the moieties given in this group. Group 33A compounds also include groups 33A-14-1, 33A-14-2, 33A-14-3, 33A-14-4, 33A-14-5, 33A-14-5A, 33A-14-6, 33A-14-7, 33A-14-8, 33A-14-8A, 33A-14-9, 33A-14-10, 33A-14-10A, 33A-14-11, 33A-14-12 and 33A-14-13, which are group 14 compounds in groups 14-1 through 14-13 where R 1 substituents 1-10 in Table A are replaced with the moieties given in this group.

Other group 33A compounds include (1) groups 33A-15-1, 33A-15-2, 33A-15-3, 33A-15-4, 33A-15-5, 33A-15-5A, 33A-15-6, 33A-15-7, 33A-15-8, 33A-15-8A, 33A-15-9, 33A-15-10, 33A-15-10A, 33A-15-11, 33A-15-12 and 33A-15-13, which are group 15 compounds in groups 15-1 through 15-13, (2) groups 33A-16-1, 33A-16-2, 33A-16-3, 33A-16-4, 33A-16-5, 33A-16-5A, 33A-16-6, 33A-16-7, 33A-16-8, 33A-16-8A, 33A-16-9, 33A-16-10, 33A-16-10A, 33A-16-11, 33A-16-12 and 33A-16-13, which are group 16 compounds in groups 16-1 through 16-13, (3) groups 33A-17-1, 33A-17-2, 33A-17-3, 33A-17-4, 33A-17-5, 33A-17-5A, 33A-17-6, 33A-17-7, 33A-17-8, 33A-17-8A, 33A-17-9, 33A-17-10, 33A-17-10A, 33A-17-11, 33A-17-12 and 33A-17-13, which are group 17 compounds in groups 17-1 through 17-13, (4) groups 33A-15-14-1, 33A-15-14-2, 33A-15-14-3, 33A-15-14-4, 33A-15-14-5, 33A-15-14-5A, 33A-15-14-6, 33A-15-14-7, 33A-15-14-8, 33A-15-14-8A, 33A-15-14-9, 33A-15-14-10, 33A-15-14-10A, 33A-15-14-11, 33A-15-14-12 and 33A-15-14-13, which are group 15 compounds in groups 15-14-1 through 15-14-13, (5) groups 33A-16-14-1, 33A-16-14-2, 33A-16-14-3, 33A-16-14-4, 33A-16-14-5, 33A-16-14-5A, 33A-16-14-6, 33A-16-14-7, 33A-16-14-8, 33A-16-14-8A, 33A-16-14-9, 33A-16-14-10, 33A-16-14-10A, 33A-16-14-11, 33A-16-14-12 and 33A-16-14-13, which are group 16 compounds in groups 16-14-1 through 16-14-13, (6) groups 33A-17-14-1, 33A-17-14-2, 33A-17-14-3, 33A-17-14-4, 33A-17-14-5, 33A-17-14-5A, 33A-17-14-6, 33A-17-14-7, 33A-17-14-8, 33A-17-14-8A, 33A-17-14-9, 33A-17-14-10, 33A-17-14-10A, 33A-17-14-11, 33A-17-14-12, 33A-17-14-13, which are group 17 compounds in groups 17-14-1 through 17-14-13, (7) groups 33A-16-15-1, 33A-16-15-2, 33A-16-15-3, 33A-16-15-4, 33A-16-15-5, 33A-16-15-5A, 33A-16-15-6, 33A-16-15-7, 33A-16-15-8, 33A-16-15-8A, 33A-16-15-9, 33A-16-15-10, 33A-16-15-10A, 33A-16-15-11, 33A-16-15-12, 33A-16-15-13, which are group 16 compounds in groups 16-15-1 through 16-15-13, (8) groups 33A-17-15-1, 33A-17-15-2, 33A-17-15-3, 33A-17-15-4, 33A-17-15-5, 33A-17-15-5A, 33A-17-15-6, 33A-17-15-7, 33A-17-15-8, 33A-17-15-8A, 33A-17-15-9, 33A-17-15-10, 33A-17-15-10A, 33A-17-15-11, 33A-17-15-12, 33A-17-15-13, which are group 17 compounds in groups 17-15-1 through 17-15-13, (9) groups 33A-17-16-1, 33A-17-16-2, 33A-17-16-3, 33A-17-16-4, 33A-17-16-5, 33A-17-16-5A, 33A-17-16-6, 33A-17-16-7, 33A-17-16-8, 33A-17-16-8A, 33A-17-16-9, 33A-17-16-10, 33A-17-16-10A, 33A-17-16-11, 33A-17-16-12, 33A-17-16-13, which are group 17 compounds in groups 17-16-1 through 17-16-13, (10) groups 33A-16-15-14-1, 33A-16-15-14-2, 33A-16-15-14-3, 33A-16-15-14-4, 33A-16-15-14-5, 33A-16-15-14-5A, 33A-16-15-14-6, 33A-16-15-14-7, 33A-16-15-14-8, 33A-16-15-14-8A, 33A-16-15-14-9, 33A-16-15-14-10, 33A-16-15-14-10A, 33A-16-15-14-11, 33A-16-15-14-12, 33A-16-15-14-13, which are group 16 compounds in groups 16-15-14-1 through 16-15-14-13, (11) groups 33A-17-15-14-1, 33A-17-15-14-2, 33A-17-15-14-3, 33A-17-15-14-4, 33A-17-15-14-5, 33A-17-15-14-5A, 33A-17-15-14-6, 33A-17-15-14-7, 33A-17-15-14-8, 33A-17-15-14-8A, 33A-17-15-14-9, 33A-17-15-14-10, 33A-17-15-14-10A, 33A-17-15-14-11, 33A-17-15-14-12, 33A-17-15-14-13, which are group 17 compounds in groups 17-15-14-1 through 17-15-14-13, (12) groups 33A-17-16-14-1, 33A-17-16-14-2, 33A-17-16-14-3, 33A-17-16-14-4, 33A-17-16-14-5, 33A-17-16-14-5A, 33A-17-16-14-6, 33A-17-16-14-7, 33A-17-16-14-8, 33A-17-16-14-8A, 33A-17-16-14-9, 33A-17-16-14-10, 33A-17-16-14-10A, 33A-17-16-14-11, 33A-17-16-14-12, 33A-17-16-14-13, which are group 17 compounds in groups 17-16-14-1 through 17-15-14-13, (13) groups 33A-17-16-15-1, 33A-17-16-15-2, 33A-17-16-15-3, 33A-17-16-15-4, 33A-17-16-15-5, 33A-17-16-15-5A, 33A-17-16-15-6, 33A-17-16-15-7, 33A-17-16-15-8, 33A-17-16-15-8A, 33A-17-16-15-9, 33A-17-16-15-10, 33A-17-16-15-10A, 33A-17-16-15-11, 33A-17-16-15-12 and 33A-17-16-15-13, which are group 17 compounds in groups 17-16-15-1 through 17-16-15-13, (14) groups 33A-17-16-15-14-1, 33A-17-16-15-14-2, 33A-17-16-15-14-3, 33A-17-16-15-14-4, 33A-17-16-15-14-5, 33A-17-16-15-14-5A, 33A-17-16-15-14-6, 33A-17-16-15-14-7, 33A-17-16-15-14-8, 33A-17-16-15-14-8A, 33A-17-16-15-14-9, 33A-17-16-15-14-10, 33A-17-16-15-14-10A, 33A-17-16-15-14-11, 33A-17-16-15-14-12 and 33A-17-16-15-14-13, which are group 17 compounds in groups 17-16-15-14-1 through 17-16-15-14-13, (15) all of the compounds and/or groups described in group 18, (16) all of the compounds and/or groups described in group 19, (17) all of the compounds and/or groups described in group 20, and (18) all of the compounds and/or groups described in groups 21, 22, 23, 24, 25, 26, 26A, 26B, 26C, 26E and 27.

Group 33B. This group contains compounds in groups 1-27 above where R 1 substituents 1-10 listed in Table A are replaced with the following groups: 1 —N-piperazine substituted at N4 with optionally substituted alkyl, 2 —N-indole, 3 —N-indoline, 4 —N-quinolidine, 5 —NH—C(O)—CH 2 —CH 2 —C(O)—OH, 6 —NH—C(O)—CH 2 —C(O)—OH, 7 —NH—C(O)—CH 2 —CH 2 —C(O)—OR PR , 8 —NH—C(O)—CH 2 —C(O)—OR PR , 9 —NH—C(O)—(CH 2 ) 3 —C(O)—OH, 10 —NH—C(O)—(CH 2 ) 3 —C(O)—OR PR . Ionizable moieties such as free carboxyl groups include salts, e.g., Na + or K + . R PR is a protecting group.

Group 33C. This group contains compounds in groups 1-27 above where R 1 substituents 1-10 listed in Table A are replaced with the following groups: 1 —NH—CH(CH 3 )—C(O)OH, 2 —NH—CH(CH 3 )—C(O)OR PR , 3 —NH—CH(CH 2 OH)—C(O)OH, 4 —NH—CH(CH 2 OH)—C(O)OR PR , 5 —NH—CH 2 —CH 2 —C(O)—OH, 6 —NH—CH 2 —C(O)—OH, 7 —NH—CH 2 —CH 2 —C(O)—OR PR , 8 —NH—CH 2 —C(O)—OR PR , 9 —NH—(CH 2 ) 3 —C(O)—OH, 10 —NH—(CH 2 ) 3 —C(O)—OR PR . Ionizable moieties such as free carboxyl groups include salts, e.g., Na + or K + . R PR is a protecting group.

Group 33D. This group contains compounds in groups 1-27 above where R 1 substituents 1-10 listed in Table A are replaced with the following groups: 1 —NH—CH(CH 3 )—C(O)OH, 2 —NH—NH—C(O)CH 3 , 3 —NH—NH—C(O)OCH 3 , 4 —NH—NH—C(O)C 2 H 5 , 5 —NH—NH—C(O)OC 2 H 5 , 6 —NH—NH—C(O)C 3 H 7 , 7 —NH—NH—C(O)-optionally substituted alkyl, 8 —NH—C(NH-optionally substituted alkyl)=N-optionally substituted alkyl, 9 —NH—C(NH—CH 3 )═N—CH 3 , 10 —NH—C(NH—C 2 H 5 )═N—C 2 H 5 .

Group 33E. This group contains compounds in groups 1-27 above where R 1 substituents 1-10 listed in Table A are replaced with the following groups: 1 spiro β-NH—(CH 2 ) 2 —O-α, 2 spiro α-NH—(CH 2 ) 2 —O-β, 3 spiro β-NH—(CH 2 ) 2 —NH-α, 4 spiro α-NH—(CH 2 ) 2 —NH-β, 5 spiro β-NH—CH═N—CH 2 -α, 6 spiro α-NH—CH═N—CH 2 -β, 7 spiro β-NH—CHR 10 —CHR 10 —O-α, 8 spiro α-NH—CHR 10 —CHR 10 —O-β, 9 spiro β-NH—CHR 10 —CHR 10 —NH-α, 10 spiro α-NH—CHR 10 —CHR 10 —NH-β. Each R 10 is independently chosen and has the meaning given above, e.g., —H, —OH, ═O, —SH, ═S, halogen or optionally substituted alkyl.

Group 34. This group contains compounds in groups 1-27 above where R 1 substituents 1-10 listed in Table A are replaced with the following groups: 1-glycol, e.g., propylene glycol or ethylene glycol, 2-polyethylene glycol, e.g., PEG 100 or PEG 200, 3 -an acetal ring, 4-a spiro ring, 5-a thioacetal ring, 6 spiro —O—CH 2 —O—, 7 spiro —O—(CH 2 ) 2 —O—, 8 spiro —NH—(CH 2 ) 2 —O—, 9 —NH—C(O)—(CH 2 ) 2 —C(O)O—CH 3 , 10 —NH—C(O)—(CH 2 ) 2 —C(O)—OH.

Group 35. This group contains compounds in groups 1-34 above where R 3 substituents 1-10 listed in Table A are replaced with the following groups: 1-optionally substituted amine, 2-optionally substituted amide, 3-optionally substituted oxime, 4 -optionally substituted alkyl, 5-optionally substituted alkenyl, 6-optionally substituted alkynyl, 7-optionally substituted aryl, 8-optionally substituted heterocycle, 9-ether and 10-ester. Any of these groups can be a moiety defined or described herein for that moiety, e.g., optionally substituted amine includes —NH 2 , —NH 3 + Cl − , —NH 3 + Br − , —NH 3 + I − , —NHCH 3 , —N(CH 3 ) 2 , —NHC 2 H 5 , —N(C 2 H 5 ) 2 , —NHC 3 H 7 , —N(C 3 H 7 ) 2 , —NHC 4 H 9 , —N(C 4 H 9 ) 2 , —NH-optionally substituted alkyl, —N(optionally substituted alkyl) 2 , —NH—C 6 H 5 , —N(C 6 H 5 ) 2 , —NH-optionally substituted monosaccharide and —NH-optionally substituted oligosaccharide, and optionally substituted amide includes —NHC(O)-optionally substituted alkyl, —N(CH 3 )—C(O)-optionally substituted alkyl, —N(C 2 H 5 )—C(O)-optionally substituted alkyl, —N(C 3 H 7 )—C(O)-optionally substituted alkyl, —N(C 4 H 9 )—C(O)-optionally substituted alkyl, —N(C 6 H 5 )—C(O)-optionally substituted alkyl, —NH—C(O)-optionally substituted monosaccharide and —NH—C(O)-optionally substituted oligosaccharide, where alkyl or phenyl groups are the same or different and are optionally substituted as described herein.

These compounds include compounds in group 35-1 through 35-34-27-20-19-18-17-16-15-14-13, which collectively are group 35 compounds. These include groups 35-1, 35-2, 35-3, 35-4, 35-5, 35-5A, 35-6, 35-7, 35-8, 35-8A, 35-9, 35-10, 35-10A, 35-11, 35-12, 35-13, which are compounds in groups 1 through 13 where R 3 substituents 1-10 in Table A are replaced with the moieties given in this group. Group 35 compounds also include groups 35-14-1, 35-14-2, 35-14-3, 35-14-4, 35-14-5, 35-14-5A, 35-14-6, 35-14-7, 35-14-8, 35-14-8A, 35-14-9, 35-14-10, 35-14-10A, 35-14-11, 35-14-12 and 35-14-13, which are group 14 compounds in groups 14-1 through 14-13 where R 3 substituents 1-10 in Table A are replaced with the moieties given in this group.

Other group 35 compounds include (1) groups 35-15-1, 35-15-2, 35-15-3, 35-15-4, 35-15-5, 35-15-5A, 35-15-6, 35-15-7, 35-15-8, 35-15-8A, 35-15-9, 35-15-10, 35-15-10A, 35-15-11, 35-15-12 and 35-15-13, which are group 15 compounds in groups 15-1 through 15-13, (2) groups 35-16-1, 35-16-2, 35-16-3, 35-16-4, 35-16-5, 35-16-5A, 35-16-6, 35-16-7, 35-16-8, 35-16-8A, 35-16-9, 35-16-10, 35-16-10A, 35-16-11, 35-16-12 and 35-16-13, which are group 16 compounds in groups 16-1 through 16-13, (3) groups 35-17-1, 35-17-2, 35-17-3, 35-17-4, 35-17-5, 35-17-5A, 35-17-6, 35-17-7, 35-17-8, 35-17-8A, 35-17-9, 35-17-10, 35-17-10A, 35-17-11, 35-17-12 and 35-17-13, which are group 17 compounds in groups 17-1 through 17-13, (4) groups 35-15-14-1, 35-15-14-2, 35-15-14-3, 35-15-14-4, 35-15-14-5, 35-15-14-5A, 35-15-14-6, 35-15-14-7, 35-15-14-8, 35-15-14-8A, 35-15-14-9, 35-15-14-10, 35-15-14-10A, 35-15-14-11, 35-15-14-12 and 35-15-14-13, which are group 15 compounds in groups 15-14-1 through 15-14-13, (5) groups 35-16-14-1, 35-16-14-2, 35-16-14-3, 35-16-14-4, 35-16-14-5, 35-16-14-5A, 35-16-14-6, 35-16-14-7, 35-16-14-8, 35-16-14-8A, 35-16-14-9, 35-16-14-10, 35-16-14-10A, 35-16-14-11, 35-16-14-12 and 35-16-14-13, which are group 16 compounds in groups 16-14-1 through 16-14-13, (6) groups 35-17-14-1, 35-17-14-2, 35-17-14-3, 35-17-14-4, 35-17-14-5, 35-17-14-5A, 35-17-14-6, 35-17-14-7, 35-17-14-8, 35-17-14-8A, 35-17-14-9, 35-17-14-10, 35-17-14-10A, 35-17-14-11, 35-17-14-12, 35-17-14-13, which are group 17 compounds in groups 17-14-1 through 17-14-13, (7) groups 35-16-15-1, 35-16-15-2, 35-16-15-3, 35-16-15-4, 35-16-15-5, 35-16-15-5A, 35-16-15-6, 35-16-15-7, 35-16-15-8, 35-16-15-8A, 35-16-15-9, 35-16-15-10, 35-16-15-10A, 35-16-15-11, 35-16-15-12, 35-16-15-13, which are group 16 compounds in groups 16-15-1 through 16-15-13, (8) groups 35-17-15-1, 35-17-15-2, 35-17-15-3, 35-17-15-4, 35-17-15-5, 35-17-15-5A, 35-17-15-6, 35-17-15-7, 35-17-15-8, 35-17-15-8A, 35-17-15-9, 35-17-15-10, 35-17-15-10A, 35-17-15-11, 35-17-15-12, 35-17-15-13, which are group 17 compounds in groups 17-15-1 through 17-15-13, (9) groups 35-17-16-1, 35-17-16-2, 35-17-16-3, 35-17-16-4, 35-17-16-5, 35-17-16-5A, 35-17-16-6, 35-17-16-7, 35-17-16-8, 35-17-16-8A, 35-17-16-9, 35-17-16-10, 35-17-16-10A, 35-17-16-11, 35-17-16-12, 35-17-16-13, which are group 17 compounds in groups 17-16-1 through 17-16-13, (10) groups 35-16-15-14-1, 35-16-15-14-2, 35-16-15-14-3, 35-16-15-14-4, 35-16-15-14-5, 35-16-15-14-5A, 35-16-15-14-6, 35-16-15-14-7, 35-16-15-14-8, 35-16-15-14-8A, 35-16-15-14-9, 35-16-15-14-10, 35-16-15-14-10A, 35-16-15-14-11, 35-16-15-14-12, 35-16-15-14-13, which are group 16 compounds in groups 16-15-14-1 through 16-15-14-13, (11) groups 35-17-15-14-1, 35-17-15-14-2, 35-17-15-14-3, 35-17-15-14-4, 35-17-15-14-5, 35-17-15-14-5A, 35-17-15-14-6, 35-17-15-14-7, 35-17-15-14-8, 35-17-15-14-8A, 35-17-15-14-9, 35-17-15-14-10, 35-17-15-14-10A, 35-17-15-14-11, 35-17-15-14-12, 35-17-15-14-13, which are group 17 compounds in groups 17-15-14-1 through 17-15-14-13, (12) groups 35-17-16-14-1, 35-17-16-14-2, 35-17-16-14-3, 35-17-16-14-4, 35-17-16-14-5, 35-17-16-14-5A, 35-17-16-14-6, 35-17-16-14-7, 35-17-16-14-8, 35-17-16-14-8A, 35-17-16-14-9, 35-17-16-14-10, 35-17-16-14-10A, 35-17-16-14-11, 35-17-16-14-12, 35-17-16-14-13, which are group 17 compounds in groups 17-16-14-1 through 17-15-14-13, (13) groups 35-17-16-15-1, 35-17-16-15-2, 35-17-16-15-3, 35-17-16-15-4, 35-17-16-15-5, 35-17-16-15-5A, 35-17-16-15-6, 35-17-16-15-7, 35-17-16-15-8, 35-17-16-15-8A, 35-17-16-15-9, 35-17-16-15-10, 35-17-16-15-10A, 35-17-16-15-11, 35-17-16-15-12 and 35-17-16-15-13, which are group 17 compounds in groups 17-16-15-1 through 17-16-15-13, (14) groups 35-17-16-15-14-1, 35-17-16-15-14-2, 35-17-16-15-14-3, 35-17-16-15-14-4, 35-17-16-15-14-5, 35-17-16-15-14-5A, 35-17-16-15-14-6, 35-17-16-15-14-7, 35-17-16-15-14-8, 35-17-16-15-14-8A, 35-17-16-15-14-9, 35-17-16-15-14-10, 35-17-16-15-14-10A, 35-17-16-15-14-11, 35-17-16-15-14-12 and 35-17-16-15-14-13, which are group 17 compounds in groups 17-16-15-14-1 through 17-16-15-14-13, (15) all of the compounds and/or groups described in group 18, (16) all of the compounds and/or groups described in group 19, (17) all of the compounds and/or groups described in group 20, (18) all of the compounds and/or groups described in groups 21, 22, 23, 24, 25, 26, 26A, 26B, 26C, 26E and 27, (19) all of the compounds and/or groups described in groups 28, 29, 30, 31, 32, 33, 33A, 33B, 33C, 33D, 33E and 34 and (20) all of the compounds and/or groups described in groups 35, 36, 37, 38, 39, 40, 40A, 40B, 40C, 40D, 40E and 41.

Group 36. This group contains compounds in groups 1-34 above where R 3 substituents 1-10 listed in Table A are replaced with the following groups: 1-acyl, 2 -thioester, 3-thioether, 4-thioacyl, 5-epoxide, 6-optionally substituted cyclopropyl, 7 —O—Si(C1-C6 alkyl) 3 , 8-phosphate, 9-phosphate ester and 10-phosphate ether. Any of these groups can be a moiety defined herein for that group. The epoxide and optionally substituted cyclopropyl moieties for substituents 5 and 6 respectively can be at the 15-16 positions or at the 16-17 positions in the α- or β-configuration.

Group 37. This group contains compounds in groups 1-34 above where R 3 substituents 1-10 listed in Table A are replaced with the following groups: 1-phosphate thioether, 2-thionoester, 3-amino acid, 4-peptide, 5-dipeptide, 6-optionally substituted heterocycle, 7-optionally substituted carboxyl, 8-carbonate, 9-carbamate and 10-phosphothioester.

Group 38. This group contains compounds in groups 1-34 above where R 3 substituents 1-10 listed in Table A are replaced with the following groups: 1 -thiophosphate, 2-phosphothioether, 3-thiophosphate thioether, 4-phosphonoester, 5 -phosphonate, 6-phosphonate ester, 7-phosphonate ether, 8-phosphonate thioether, 9 —O—S(O)(O)—OH and 10-sulfate salt, e.g., —O—S(O)(O)—O + Na − .

Group 39. This group contains compounds in groups 1-34 above where R 3 substituents 1-10 listed in Table A are replaced with the following groups: 1-sulfate ester, 2-sulfate ether, 3-sulfate thioether, 4 —O—S(O)—OH, 5-sulfite salt, e.g., —O—S(O)—O + Na − , 6 -sulfite ester, 7-sulfite ether, 8-sulfoxide, 9 —O—S(O)(O)—OR PR and 10 —O—S(O)(O)—OCH 3 .

Group 40. This group contains compounds in groups 1-34 above where R 3 substituents 1-10 listed in Table A are replaced with the following groups: 1-sulfonamide, 2-sulfonamide derivative, e.g., —S(O)(O)—NHR PR or —S(O)(O)—NH-optionally substituted alkyl, 3-sulfamate, 4-sulfamate derivative, e.g., —O—S(O)(O)—NHR PR , —O—S(O)(O)—NHCH 3 , —O—S(O)(O)—NHC 2 H 5 , —O—S(O)(O)—NHC 3 H 7 , —O—S(O)(O)—NHC 4 H 9 , —O—S(O)(O)—N(RD) 2 or —O—S(O)(O)—NH-optionally substituted alkyl, 5-sulfonate, 6-sulfamide, 7-sulfinamide, 8 -sulfurous diamide, 9-optionally protected monosaccharide, e.g., D-, L- or DL-glucose, fructose, rhamnose or glucuronic acid, 10-optionally protected oligosaccharide, e.g., D-, L- or DL-galactose-galactose, -galactose-mannose or -glucuronic acid-glucose. In this group, the optionally protected monosaccharide and optionally protected oligomonosaccharide moieties are typically linked to the 3-position through an oxygen, sulfur or nitrogen atom.

Exemplary group 40 compounds include glycosides such as 16β-glycosides and 16α-glycosides, 3β, 17β-dihydroxyandrost-5-ene-16α-O-1′-β′-glucopyranose, 3α, 17β-dihydroxyandrost-5-ene-16β-O-1′-β′-glucopyranose, 3β-hydroxy-17-oxoandrost-5-ene-16β-O-1′-β′-glucopyranose, 3β, 17α-dihydroxyandrost-5-ene-16α-1′-β′-glucopyranose, 3α, 17α-dihydroxyandrost-5-ene-16β-O-1′-β′-glucopyranose, 3β-hydroxy-74-fluoro-17-oxoandrost-5-ene-17α-1′-β′-glucopyranose and analogs of any of these compounds having one, two or more moieties described herein for variable groups, e.g., 16α-halo, 16β-halo, 7α-hydroxy or thiol, 7β-hydroxy or thiol, 7-oxo, 7α-halo, 7β-halo, 7α-fluoro, 7β-fluoro, 7α-alkoxy, 7β-alkoxy, 4α-halo, 4β-halo, 4α-alkyl, 4β-alkyl, 12α-halo, 12β-halo, 12-dialkyl, 12α-alkyl, 12β-alkyl, 11-dihalo, 11-alkyl, 11α-alkyl, 11-dialkyl, 2-oxa, 11-oxa, 15-oxa, 19-nor (i.e., R 6 is —H), 18-homo (i.e., R 5 is —C 2 H 5 ) or the like where any alkyl or alkoxy moieties are optionally substituted. Other exemplary moieties at R 3 include β-D-glucopyranosyl, β-D-glucopyranuronosyl, β-D-2-acetamido-2-deoxy-glucopyranosyl, β-D-galactopyranosyl, β-D-fucopyranosyl, β-L-fucopyranosyl, α-D-fructofuranosyl, β-D-fructofuranosyl, β-D-xylopyranosyl, β-L-xylopyranosyl, α-D-arabanopyranosyl, α-L-arabanopyranosyl, α-L-rhamnopyranosyl, α-D-rhamnopyranosyl, α-D-cellobiosyl, β-D-cellobiosyl, β-D-lactosyl, β-D-maltosyl, β-D-gentiobiosyl, 3-O-β-D-galactopyranosyl-α-D-arabanopyranosyl or β-D-maltotriosyl, any of which are optionally protected and where R 3 is in the α- or β-configuration.

These compounds include compounds in group 40-1 through 40-41-34-27-20-19-18-17-16-15-14-13, which collectively are group 40 compounds. These include groups 40-1, 40-2, 40-3, 40-4, 40-5, 40-5A, 40-6, 40-7, 40-8, 40-8A, 40-9, 40-10, 40-10A, 40-11, 40-12, 40-13, which are compounds in groups 1 through 13 where R 3 substituents 1-10 in Table A are replaced with the moieties given in this group. Group 40 compounds also include groups 40-14-1, 40-14-2, 40-14-3, 40-14-4, 40-14-5, 40-14-5A, 40-14-6, 40-14-7, 40-14-8, 40-14-8A, 40-14-9, 40-14-10, 40-14-10A, 40-14-11, 40-14-12 and 40-14-13, which are group 14 compounds in groups 14-1 through 14-13 where R 3 substituents 1-10 in Table A are replaced with the moieties given in this group.

Other group 40 compounds include (1) groups 40-15-1, 40-15-2, 40-15-3, 40-15-4, 40-15-5, 40-15-5A, 40-15-6, 40-15-7, 40-15-8, 40-15-8A, 40-15-9, 40-15-10, 40-15-10A, 40-15-11, 40-15-12 and 40-15-13, which are group 15 compounds in groups 15-1 through 15-13, (2) groups 40-16-1, 40-16-2, 40-16-3, 40-16-4, 40-16-5, 40-16-5A, 40-16-6, 40-16-7, 40-16-8, 40-16-8A, 40-16-9, 40-16-10, 40-16-10A, 40-16-11, 40-16-12 and 40-16-13, which are group 16 compounds in groups 16-1 through 16-13, (3) groups 40-17-1, 40-17-2, 40-17-3, 40-17-4, 40-17-5, 40-17-5A, 40-17-6, 40-17-7, 40-17-8, 40-17-8A, 40-17-9, 40-17-10, 40-17-10A, 40-17-11, 40-17-12 and 40-17-13, which are group 17 compounds in groups 17-1 through 17-13, (4) groups 40-15-14-1, 40-15-14-2, 40-15-14-3, 40-15-14-4, 40-15-14-5, 40-15-14-5A, 40-15-14-6, 40-15-14-7, 40-15-14-8, 40-15-14-8A, 40-15-14-9, 40-15-14-10, 40-15-14-10A, 40-15-14-11, 40-15-14-12 and 40-15-14-13, which are group 15 compounds in groups 15-14-1 through 15-14-13, (5) groups 40-16-14-1, 40-16-14-2, 40-16-14-3, 40-16-14-4, 40-16-14-5, 40-16-14-5A, 40-16-14-6, 40-16-14-7, 40-16-14-8, 40-16-14-8A, 40-16-14-9, 40-16-14-10, 40-16-14-10A, 40-16-14-11, 40-16-14-12 and 40-16-14-13, which are group 16 compounds in groups 16-14-1 through 16-14-13, (6) groups 40-17-14-1, 40-17-14-2, 40-17-14-3, 40-17-14-4, 40-17-14-5, 40-17-14-5A, 40-17-14-6, 40-17-14-7, 40-17-14-8, 40-17-14-8A, 40-17-14-9, 40-17-14-10, 40-17-14-10A, 40-17-14-11, 40-17-14-12, 40-17-14-13, which are group 17 compounds in groups 17-14-1 through 17-14-13, (7) groups 40-16-15-1, 40-16-15-2, 40-16-15-3, 40-16-15-4, 40-16-15-5, 40-16-15-5A, 40-16-15-6, 40-16-15-7, 40-16-15-8, 40-16-15-8A, 40-16-15-9, 40-16-15-10, 40-16-15-10A, 40-16-15-11, 40-16-15-12, 40-16-15-13, which are group 16 compounds in groups 16-15-1 through 16-15-13, (8) groups 40-17-15-1, 40-17-15-2, 40-17-15-3, 40-17-15-4, 40-17-15-5, 40-17-15-5A, 40-17-15-6, 40-17-15-7, 40-17-15-8, 40-17-15-8A, 40-17-15-9, 40-17-15-10, 40-17-15-10A, 40-17-15-11, 40-17-15-12, 40-17-15-13, which are group 17 compounds in groups 17-15-1 through 17-15-13, (9) groups 40-17-16-1, 40-17-16-2, 40-17-16-3, 40-17-16-4, 40-17-16-5, 40-17-16-5A, 40-17-16-6, 40-17-16-7, 40-17-16-8, 40-17-16-8A, 40-17-16-9, 40-17-16-10, 40-17-16-10A, 40-17-16-11, 40-17-16-12, 40-17-16-13, which are group 17 compounds in groups 17-16-1 through 17-16-13, (10) groups 40-16-15-14-1, 40-16-15-14-2, 40-16-15-14-3, 40-16-15-14-4, 40-16-15-14-5, 40-16-15-14-5A, 40-16-15-14-6, 40-16-15-14-7, 40-16-15-14-8, 40-16-15-14-8A, 40-16-15-14-9, 40-16-15-14-10, 40-16-15-14-10A, 40-16-15-14-11, 40-16-15-14-12, 40-16-15-14-13, which are group 16 compounds in groups 16-15-14-1 through 16-15-14-13, (11) groups 40-17-15-14-1, 40-17-15-14-2, 40-17-15-14-3, 40-17-15-14-4, 40-17-15-14-5, 40-17-15-14-5A, 40-17-15-14-6, 40-17-15-14-7, 40-17-15-14-8, 40-17-15-14-8A, 40-17-15-14-9, 40-17-15-14-10, 40-17-15-14-10A, 40-17-15-14-11, 40-17-15-14-12, 40-17-15-14-13, which are group 17 compounds in groups 17-15-14-1 through 17-15-14-13, (12) groups 40-17-16-14-1, 40-17-16-14-2, 40-17-16-14-3, 40-17-16-14-4, 40-17-16-14-5, 40-17-16-14-5A, 40-17-16-14-6, 40-17-16-14-7, 40-17-16-14-8, 40-17-16-14-8A, 40-17-16-14-9, 40-17-16-14-10, 40-17-16-14-10A, 40-17-16-14-11, 40-17-16-14-12, 40-17-16-14-13, which are group 17 compounds in groups 17-16-14-1 through 17-15-14-13, (13) groups 40-17-16-15-1, 40-17-16-15-2, 40-17-16-15-3, 40-17-16-15-4, 40-17-16-15-5, 40-17-16-15-5A, 40-17-16-15-6, 40-17-16-15-7, 40-17-16-15-8, 40-17-16-15-8A, 40-17-16-15-9, 40-17-16-15-10, 40-17-16-15-10A, 40-17-16-15-11, 40-17-16-15-12 and 40-17-16-15-13, which are group 17 compounds in groups 17-16-15-1 through 17-16-15-13, (14) groups 40-17-16-15-14-1, 40-17-16-15-14-2, 40-17-16-15-14-3, 40-17-16-15-14-4, 40-17-16-15-14-5, 40-17-16-15-14-5A, 40-17-16-15-14-6, 40-17-16-15-14-7, 40-17-16-15-14-8, 40-17-16-15-14-8A, 40-17-16-15-14-9, 40-17-16-15-14-10, 40-17-16-15-14-10A, 40-17-16-15-14-11, 40-17-16-15-14-12 and 40-17-16-15-14-13, which are group 17 compounds in groups 17-16-15-14-1 through 17-16-15-14-13, (15) all of the compounds and/or groups described in group 18, (16) all of the compounds and/or groups described in group 19, (17) all of the compounds and/or groups described in group 20, (18) all of the compounds and/or groups described in groups 21, 22, 23, 24, 25, 26, 26A, 26B, 26C, 26E and 27, (19) all of the compounds and/or groups described in groups 28, 29, 30, 31, 32, 33, 33A, 33B, 33C, 33D, 33E and 34 and (20) all of the compounds and/or groups described in groups 35, 36, 37, 38, 39, 40, 40A, 40B, 40C, 40D, 40E and 41.

Group 40A. This group contains compounds in groups 1-34 above where R 3 substituents 1-10 listed in Table A are replaced with the following groups: 1 —N-pyrrolidine, 2 —N1-pyrazolone, 3 —N2-pyrazolone, 4 —N-imidazolidin-2-one, 5 —N1-imidazole, 6 —N1-4,5-dihydroimidazole, 7 —N-morpholine, 8 —N1-pyridine, 9 —N-piperidine, 10 —N-piperazine. The compounds in this group are described as in other groups described above, e.g., group 40A-3 compound 1.1.1.9 (i.e., group 40A compound 1.1.1.9 from group 3) is 16α-N-pyrrolidinyl-3β, 17β-dihydroxyandrost-5-ene.

These compounds include compounds in group 40A-1 through 40A-41-34-27-20-19-18-17-16-15-14-13, which collectively are group 40A compounds. These include groups 40A-1, 40A-2, 40A-3, 40A-4, 40A-5, 40A-5A, 40A-6, 40A-7, 40A-8, 40A-8A, 40A-9, 40A-10, 40A-10A, 40A-11, 40A-12, 40A-13, which are compounds in groups 1 through 13 where R 3 substituents 1-10 in Table A are replaced with the moieties given in this group. Group 40A compounds also include groups 40A-14-1, 40A-14-2, 40A-14-3, 40A-14-4, 40A-14-5, 40A-14-5A, 40A-14-6, 40A-14-7, 40A-14-8, 40A-14-8A, 40A-14-9, 40A-14-10, 40A-14-10A, 40A-14-11, 40A-14-12 and 40A-14-13, which are group 14 compounds in groups 14-1 through 14-13 where R 3 substituents 1-10 in Table A are replaced with the moieties given in this group.

Other group 40A compounds include (1) groups 40A-15-1, 40A-15-2, 40A-15-3, 40A-15-4, 40A-15-5, 40A-15-5A, 40A-15-6, 40A-15-7, 40A-15-8, 40A-15-8A, 40A-15-9, 40A-15-10, 40A-15-10A, 40A-15-11, 40A-15-12 and 40A-15-13, which are group 15 compounds in groups 15-1 through 15-13, (2) groups 40A-16-1, 40A-16-2, 40A-16-3, 40A-16-4, 40A-16-5, 40A-16-5A, 40A-16-6, 40A-16-7, 40A-16-8, 40A-16-8A, 40A-16-9, 40A-16-10, 40A-16-10A, 40A-16-11, 40A-16-12 and 40A-16-13, which are group 16 compounds in groups 16-1 through 16-13, (3) groups 40A-17-1, 40A-17-2, 40A-17-3, 40A-17-4, 40A-17-5, 40A-17-5A, 40A-17-6, 40A-17-7, 40A-17-8, 40A-17-8A, 40A-17-9, 40A-17-10, 40A-17-10A, 40A-17-11, 40A-17-12 and 40A-17-13, which are group 17 compounds in groups 17-1 through 17-13, (4) groups 40A-15-14-1, 40A-15-14-2, 40A-15-14-3, 40A-15-14-4, 40A-15-14-5, 40A-15-14-5A, 40A-15-14-6, 40A-15-14-7, 40A-15-14-8, 40A-15-14-8A, 40A-15-14-9, 40A-15-14-10, 40A-15-14-10A, 40A-15-14-11, 40A-15-14-12 and 40A-15-14-13, which are group 15 compounds in groups 15-14-1 through 15-14-13, (5) groups 40A-16-14-1, 40A-16-14-2, 40A-16-14-3, 40A-16-14-4, 40A-16-14-5, 40A-16-14-5A, 40A-16-14-6, 40A-16-14-7, 40A-16-14-8, 40A-16-14-8A, 40A-16-14-9, 40A-16-14-10, 40A-16-14-10A, 40A-16-14-11, 40A-16-14-12 and 40A-16-14-13, which are group 16 compounds in groups 16-14-1 through 16-14-13, (6) groups 40A-17-14-1, 40A-17-14-2, 40A-17-14-3, 40A-17-14-4, 40A-17-14-5, 40A-17-14-5A, 40A-17-14-6, 40A-17-14-7, 40A-17-14-8, 40A-17-14-8A, 40A-17-14-9, 40A-17-14-10, 40A-17-14-10A, 40A-17-14-11, 40A-17-14-12, 40A-17-14-13, which are group 17 compounds in groups 17-14-1 through 17-14-13, (7) groups 40A-16-15-1, 40A-16-15-2, 40A-16-15-3, 40A-16-15-4, 40A-16-15-5, 40A-16-15-5A, 40A-16-15-6, 40A-16-15-7, 40A-16-15-8, 40A-16-15-8A, 40A-16-15-9, 40A-16-15-10, 40A-16-15-10A, 40A-16-15-11, 40A-16-15-12, 40A-16-15-13, which are group 16 compounds in groups 16-15-1 through 16-15-13, (8) groups 40A-17-15-1, 40A-17-15-2, 40A-17-15-3, 40A-17-15-4, 40A-17-15-5, 40A-17-15-5A, 40A-17-15-6, 40A-17-15-7, 40A-17-15-8, 40A-17-15-8A, 40A-17-15-9, 40A-17-15-10, 40A-17-15-10A, 40A-17-15-11, 40A-17-15-12, 40A-17-15-13, which are group 17 compounds in groups 17-15-1 through 17-15-13, (9) groups 40A-17-16-1, 40A-17-16-2, 40A-17-16-3, 40A-17-16-4, 40A-17-16-5, 40A-17-16-5A, 40A-17-16-6, 40A-17-16-7, 40A-17-16-8, 40A-17-16-8A, 40A-17-16-9, 40A-17-16-10, 40A-17-16-10A, 40A-17-16-11, 40A-17-16-12, 40A-17-16-13, which are group 17 compounds in groups 17-16-1 through 17-16-13, (10) groups 40A-16-15-14-1, 40A-16-15-14-2, 40A-16-15-14-3, 40A-16-15-14-4, 40A-16-15-14-5, 40A-16-15-14-5A, 40A-16-15-14-6, 40A-16-15-14-7, 40A-16-15-14-8, 40A-16-15-14-8A, 40A-16-15-14-9, 40A-16-15-14-10, 40A-16-15-14-10A, 40A-16-15-14-11, 40A-16-15-14-12, 40A-16-15-14-13, which are group 16 compounds in groups 16-15-14-1 through 16-15-14-13, (11) groups 40A-17-15-14-1, 40A-17-15-14-2, 40A-17-15-14-3, 40A-17-15-14-4, 40A-17-15-14-5, 40A-17-15-14-5A, 40A-17-15-14-6, 40A-17-15-14-7, 40A-17-15-14-8, 40A-17-15-14-8A, 40A-17-15-14-9, 40A-17-15-14-10, 40A-17-15-14-10A, 40A-17-15-14-11, 40A-17-15-14-12, 40A-17-15-14-13, which are group 17 compounds in groups 17-15-14-1 through 17-15-14-13, (12) groups 40A-17-16-14-1, 40A-17-16-14-2, 40A-17-16-14-3, 40A-17-16-14-4, 40A-17-16-14-5, 40A-17-16-14-5A, 40A-17-16-14-6, 40A-17-16-14-7, 40A-17-16-14-8, 40A-17-16-14-8A, 40A-17-16-14-9, 40A-17-16-14-10, 40A-17-16-14-10A, 40A-17-16-14-11, 40A-17-16-14-12, 40A-17-16-14-13, which are group 17 compounds in groups 17-16-14-1 through 17-15-14-13, (13) groups 40A-17-16-15-1, 40A-17-16-15-2, 40A-17-16-15-3, 40A-17-16-15-4, 40A-17-16-15-5, 40A-17-16-15-5A, 40A-17-16-15-6, 40A-17-16-15-7, 40A-17-16-15-8, 40A-17-16-15-8A, 40A-17-16-15-9, 40A-17-16-15-10, 40A-17-16-15-10A, 40A-17-16-15-11, 40A-17-16-15-12 and 40A-17-16-15-13, which are group 17 compounds in groups 17-16-15-1 through 17-16-15-13, (14) groups 40A-17-16-15-14-1, 40A-17-16-15-14-2, 40A-17-16-15-14-3, 40A-17-16-15-14-4, 40A-17-16-15-14-5, 40A-17-16-15-14-5A, 40A-17-16-15-14-6, 40A-17-16-15-14-7, 40A-17-16-15-14-8, 40A-17-16-15-14-8A, 40A-17-16-15-14-9, 40A-17-16-15-14-10, 40A-17-16-15-14-10A, 40A-17-16-15-14-11, 40A-17-16-15-14-12 and 40A-17-16-15-14-13, which are group 17 compounds in groups 17-16-15-14-1 through 17-16-15-14-13, (15) all of the compounds and/or groups described in group 18, (16) all of the compounds and/or groups described in group 19, (17) all of the compounds and/or groups described in group 20, (18) all of the compounds and/or groups described in groups 21, 22, 23, 24, 25, 26, 26A, 26B, 26C, 26E and 27, (19) all of the compounds and/or groups described in groups 28, 29, 30, 31, 32, 33, 33A, 33B, 33C, 33D, 33E and 34 and (20) all of the compounds and/or groups described in groups 35, 36, 37, 38, 39, 40, 40A, 40B, 40C, 40D, 40E and 41.

Group 40B. This group contains compounds in groups 1-34 above where R 3 substituents 1-10 listed in Table A are replaced with the following groups: 1 —N-piperazine substituted at N4 with optionally substituted alkyl, 2 —N-indole, 3 —N-indoline, 4 —N-quinolidine, 5 —NH—C(O)—CH 2 —CH 2 —C(O)—OH, 6 —NH—C(O)—CH 2 —C(O)—OH, 7 —NH—C(O)—CH 2 —CH 2 —C(O)—OR PR , 8 —NH—C(O)—CH 2 —C(O)—OR PR , 9 —NH—C(O)—(CH 2 ) 3 —C(O)—OH, 10 —NH—C(O)—(CH 2 ) 3 —C(O)—OR PR . Ionizable moieties such as free carboxyl groups include salts, e.g., Na + or K + . R PR is a protecting group.

Group 40C. This group contains compounds in groups 1-34 above where R 3 substituents 1-10 listed in Table A are replaced with the following groups: 1 —NH—CH(CH 3 )—C(O)OH, 2 —NH—CH(CH 3 )—C(O)OR PR , 3 —NH—CH(CH 2 OH)—C(O)OH, 4 —NH—CH(CH 2 OH)—C(O)OR PR , 5 —NH—CH 2 —CH 2 —C(O)—OH, 6 —NH—CH 2 —C(O)—OH, 7 —NH—CH 2 —CH 2 —C(O)—OR PR , 8 —NH—CH 2 —C(O)—OR PR , 9 —NH—(CH 2 ) 3 —C(O)—OH, 10 —NH—(CH 2 ) 3 —C(O)—OR PR . Ionizable moieties such as free carboxyl groups include salts, e.g., Na + or K + . R PR is a protecting group.

Group 40D. This group contains compounds in groups 1-34 above where R 3 substituents 1-10 listed in Table A are replaced with the following groups: 1 —NH—CH(CH 3 )—C(O)OH, 2 —NH—NH—C(O)CH 3 , 3 —NH—NH—C(O)OCH 3 , 4 —NH—NH—C(O)C 2 H 5 , 5 —NH—NH—C(O)OC 2 H 5 , 6 —NH—NH—C(O)C 3 H 7 , 7 —NH—NH—C(O)-optionally substituted alkyl, 8 —NH—C(NH-optionally substituted alkyl)=N-optionally substituted alkyl, 9 —NH—C(NH—CH 3 )═N—CH 3 , 10 —NH—C(NH—C 2 H 5 )═N—C 2 H 5 .

Group 40E. This group contains compounds in groups 1-34 above where R 3 substituents 1-10 listed in Table A are replaced with the following groups: 1 spiro β-NH—(CH 2 ) 2 —O-α, 2 spiro α-NH—(CH 2 ) 2 —O-β, 3 spiro β-NH—(CH 2 ) 2 —NH-α, 4 spiro α-NH—(CH 2 ) 2 —NH-β, 5 spiro β-NH—CH═N—CH 2 -α, 6 spiro α-NH—CH═N—CH 2 -β, 7 spiro β-NH—CHR 10 —CHR 10 —O-α, 8 spiro α-NH—CHR 10 —CHR 10 —O-β, 9 spiro β-NH—CHR 10 —CHR 10 —NH-α, 10 spiro α-NH—CHR 10 —CHR 10 —NH—O—. Each R 10 is independently chosen and has the meaning given above, e.g., —H, —OH, ═O, —SH, ═S, halogen or optionally substituted alkyl.

Group 41. This group contains compounds in groups 1-34 above where R 3 substituents 1-10 listed in Table A are replaced with the following groups: 1-glycol, e.g., propylene glycol or ethylene glycol, 2-polyethylene glycol, e.g., PEG 100 or PEG 200, 3 -an acetal ring, 4-a spiro ring, 5-a thioacetal ring, 6 spiro —O—CH 2 —O—, 7 spiro —O—(CH 2 ) 2 —O—, 8 spiro —NH—(CH 2 ) 2 —O—, 9 —NH—C(O)—(CH 2 ) 2 —C(O)O—CH 3 , 10 —NH—C(O)—(CH 2 ) 2 —C(O)—OH.

Group 42. This group contains compounds in groups 1-41 above where R 2 substituents 1-10 listed in Table A are replaced with the following groups: 1-optionally substituted amine, 2-optionally substituted amide, 3-optionally substituted oxime, 4 -optionally substituted alkyl, 5-optionally substituted alkenyl, 6-optionally substituted alkynyl, 7-optionally substituted aryl, 8-optionally substituted heterocycle, 9-ether and 10-ester. Any of these groups can be a moiety defined or described herein for that moiety, e.g., optionally substituted amine includes —NH 2 , —NH 3 + Cl − , —NH 3 + Br − , —NH 3 + I − , —NHCH 3 , —N(CH 3 ) 2 , —NHC 2 H 5 , —N(C 2 H 5 ) 2 , —NHC 3 H 7 , —N(C 3 H 7 ) 2 , —NHC 4 H 9 , —N(C 4 H 9 ) 2 , —NH-optionally substituted alkyl, —N(optionally substituted alkyl) 2 , —NH—C 6 H 5 , —N(C 6 H 5 ) 2 , —NH-optionally substituted monosaccharide and —NH-optionally substituted oligosaccharide, and optionally substituted amide includes —NHC(O)-optionally substituted alkyl, —N(CH 3 )—C(O)-optionally substituted alkyl, —N(C 2 H 5 )—C(O)-optionally substituted alkyl, —N(C 3 H 7 )—C(O)-optionally substituted alkyl, —N(C 4 H 9 )—C(O)-optionally substituted alkyl, —N(C 6 H 5 )—C(O)-optionally substituted alkyl, —NH—C(O)-optionally substituted monosaccharide and —NH—C(O)-optionally substituted oligosaccharide, where alkyl or phenyl groups are the same or different and are optionally substituted as described herein.

These compounds include compounds in group 42-1 through 42-41-34-27-20-19-18-17-16-15-14-13, which collectively are group 42 compounds. These include groups 42-1, 42-2, 42-3, 42-4, 42-5, 42-5A, 42-6, 42-7, 42-8, 42-8A, 42-9, 42-10, 42-10A, 42-11, 42-12, 42-13, which are compounds in groups 1 through 13 where R 2 substituents 1-10 in Table A are replaced with the moieties given in this group. Group 42 compounds also include groups 42-14-1, 42-14-2, 42-14-3, 42-14-4, 42-14-5, 42-14-5A, 42-14-6, 42-14-7, 42-14-8, 42-14-8A, 42-14-9, 42-14-10, 42-14-10A, 42-14-11, 42-14-12 and 42-14-13, which are group 14 compounds in groups 14-1 through 14-13 where R 2 substituents 1-10 in Table A are replaced with the moieties given in this group.

Other group 42 compounds include (1) groups 42-15-1, 42-15-2, 42-15-3, 42-15-4, 42-15-5, 42-15-5A, 42-15-6, 42-15-7, 42-15-8, 42-15-8A, 42-15-9, 42-15-10, 42-15-10A, 42-15-11, 42-15-12 and 42-15-13, which are group 15 compounds in groups 15-1 through 15-13, (2) groups 42-16-1, 42-16-2, 42-16-3, 42-16-4, 42-16-5, 42-16-5A, 42-16-6, 42-16-7, 42-16-8, 42-16-8A, 42-16-9, 42-16-10, 42-16-10A, 42-16-11, 42-16-12 and 42-16-13, which are group 16 compounds in groups 16-1 through 16-13, (3) groups 42-17-1, 42-17-2, 42-17-3, 42-17-4, 42-17-5, 42-17-5A, 42-17-6, 42-17-7, 42-17-8, 42-17-8A, 42-17-9, 42-17-10, 42-17-10A, 42-17-11, 42-17-12 and 42-17-13, which are group 17 compounds in groups 17-1 through 17-13, (4) groups 42-15-14-1, 42-15-14-2, 42-15-14-3, 42-15-14-4, 42-15-14-5, 42-15-14-5A, 42-15-14-6, 42-15-14-7, 42-15-14-8, 42-15-14-8A, 42-15-14-9, 42-15-14-10, 42-15-14-10A, 42-15-14-11, 42-15-14-12 and 42-15-14-13, which are group 15 compounds in groups 15-14-1 through 15-14-13, (5) groups 42-16-14-1, 42-16-14-2, 42-16-14-3, 42-16-14-4, 42-16-14-5, 42-16-14-5A, 42-16-14-6, 42-16-14-7, 42-16-14-8, 42-16-14-8A, 42-16-14-9, 42-16-14-10, 42-16-14-10A, 42-16-14-11, 42-16-14-12 and 42-16-14-13, which are group 16 compounds in groups 16-14-1 through 16-14-13, (6) groups 42-17-14-1, 42-17-14-2, 42-17-14-3, 42-17-14-4, 42-17-14-5, 42-17-14-5A, 42-17-14-6, 42-17-14-7, 42-17-14-8, 42-17-14-8A, 42-17-14-9, 42-17-14-10, 42-17-14-10A, 42-17-14-11, 42-17-14-12, 42-17-14-13, which are group 17 compounds in groups 17-14-1 through 17-14-13, (7) groups 42-16-15-1, 42-16-15-2, 42-16-15-3, 42-16-15-4, 42-16-15-5, 42-16-15-5A, 42-16-15-6, 42-16-15-7, 42-16-15-8, 42-16-15-8A, 42-16-15-9, 42-16-15-10, 42-16-15-10A, 42-16-15-11, 42-16-15-12, 42-16-15-13, which are group 16 compounds in groups 16-15-1 through 16-15-13, (8) groups 42-17-15-1, 42-17-15-2, 42-17-15-3, 42-17-15-4, 42-17-15-5, 42-17-15-5A, 42-17-15-6, 42-17-15-7, 42-17-15-8, 42-17-15-8A, 42-17-15-9, 42-17-15-10, 42-17-15-10A, 42-17-15-11, 42-17-15-12, 42-17-15-13, which are group 17 compounds in groups 17-15-1 through 17-15-13, (9) groups 42-17-16-1, 42-17-16-2, 42-17-16-3, 42-17-16-4, 42-17-16-5, 42-17-16-5A, 42-17-16-6, 42-17-16-7, 42-17-16-8, 42-17-16-8A, 42-17-16-9, 42-17-16-10, 42-17-16-10A, 42-17-16-11, 42-17-16-12, 42-17-16-13, which are group 17 compounds in groups 17-16-1 through 17-16-13, (10) groups 42-16-15-14-1, 42-16-15-14-2, 42-16-15-14-3, 42-16-15-14-4, 42-16-15-14-5, 42-16-15-14-5A, 42-16-15-14-6, 42-16-15-14-7, 42-16-15-14-8, 42-16-15-14-8A, 42-16-15-14-9, 42-16-15-14-10, 42-16-15-14-10A, 42-16-15-14-11, 42-16-15-14-12, 42-16-15-14-13, which are group 16 compounds in groups 16-15-14-1 through 16-15-14-13, (11) groups 42-17-15-14-1, 42-17-15-14-2, 42-17-15-14-3, 42-17-15-14-4, 42-17-15-14-5, 42-17-15-14-5A, 42-17-15-14-6, 42-17-15-14-7, 42-17-15-14-8, 42-17-15-14-8A, 42-17-15-14-9, 42-17-15-14-10, 42-17-15-14-10A, 42-17-15-14-11, 42-17-15-14-12, 42-17-15-14-13, which are group 17 compounds in groups 17-15-14-1 through 17-15-14-13, (12) groups 42-17-16-14-1, 42-17-16-14-2, 42-17-16-14-3, 42-17-16-14-4, 42-17-16-14-5, 42-17-16-14-5A, 42-17-16-14-6, 42-17-16-14-7, 42-17-16-14-8, 42-17-16-14-8A, 42-17-16-14-9, 42-17-16-14-10, 42-17-16-14-10A, 42-17-16-14-11, 42-17-16-14-12, 42-17-16-14-13, which are group 17 compounds in groups 17-16-14-1 through 17-15-14-13, (13) groups 42-17-16-15-1, 42-17-16-15-2, 42-17-16-15-3, 42-17-16-15-4, 42-17-16-15-5, 42-17-16-15-5A, 42-17-16-15-6, 42-17-16-15-7, 42-17-16-15-8, 42-17-16-15-8A, 42-17-16-15-9, 42-17-16-15-10, 42-17-16-15-10A, 42-17-16-15-11, 42-17-16-15-12 and 42-17-16-15-13, which are group 17 compounds in groups 17-16-15-1 through 17-16-15-13, (14) groups 42-17-16-15-14-1, 42-17-16-15-14-2, 42-17-16-15-14-3, 42-17-16-15-14-4, 42-17-16-15-14-5, 42-17-16-15-14-5A, 42-17-16-15-14-6, 42-17-16-15-14-7, 42-17-16-15-14-8, 42-17-16-15-14-8A, 42-17-16-15-14-9, 42-17-16-15-14-10, 42-17-16-15-14-10A, 42-17-16-15-14-11, 42-17-16-15-14-12 and 42-17-16-15-14-13, which are group 17 compounds in groups 17-16-15-14-1 through 17-16-15-14-13, (15) all of the compounds and/or groups described in group 18, (16) all of the compounds and/or groups described in group 19, (17) all of the compounds and/or groups described in group 20, (18) all of the compounds and/or groups described in groups 21, 22, 23, 24, 25, 26, 26A, 26B, 26C, 26E and 27, (19) all of the compounds and/or groups described in groups 28, 29, 30, 31, 32, 33, 33A, 33B, 33C, 33D, 33E and 34 and (20) all of the compounds and/or groups described in groups 35, 36, 37, 38, 39, 40, 40A, 40B, 40C, 40D, 40E and 41.

Group 43. This group contains compounds in groups 1-41 above where R 2 substituents 1-10 listed in Table A are replaced with the following groups: 1-acyl, 2 -thioester, 3-thioether, 4-thioacyl, 5-epoxide, 6-optionally substituted cyclopropyl, 7 —O—Si(C1-C6 alkyl) 3 , 8-phosphate, 9-phosphate ester and 10-phosphate ether. Any of these groups can be a moiety defined herein for that group. The epoxide and optionally substituted cyclopropyl moieties for substituents 5 and 6 respectively can be at the 6-7 positions or at the 7-8 positions in the α- or β-configuration.

Group 44. This group contains compounds in groups 1-41 above where R 2 substituents 1-10 listed in Table A are replaced with the following groups: 1-phosphate thioether, 2-thionoester, 3-amino acid, 4-peptide, 5-dipeptide, 6-optionally substituted heterocycle, 7-optionally substituted carboxyl, 8-carbonate, 9-carbamate and 10-phosphothioester.

Group 45. This group contains compounds in groups 1-41 above where R 2 substituents 1-10 listed in Table A are replaced with the following groups: 1 -thiophosphate, 2-phosphothioether, 3-thiophosphate thioether, 4-phosphonoester, 5 -phosphonate, 6-phosphonate ester, 7-phosphonate ether, 8-phosphonate thioether, 9 —O—S(O)(O)—OH and 10-sulfate salt, e.g., —O—S(O)(O)—O + Na − .

Group 46. This group contains compounds in groups 1-41 above where R 2 substituents 1-10 listed in Table A are replaced with the following groups: 1-sulfate ester, 2-sulfate ether, 3-sulfate thioether, 4 —O—S(O)—OH, 5-sulfite salt, e.g., —O—S(O)—O + Na − , 6 -sulfite ester, 7-sulfite ether, 8-sulfoxide, 9 —O—S(O)(O)—OR PR , and 10 —O—S(O)(O)—OCH 3 .

Group 47. This group contains compounds in groups 1-41 above where R 2 substituents 1-10 listed in Table A are replaced with the following groups: 1-sulfonamide, 2-sulfonamide derivative, e.g., —S(O)(O)—NHR PR or —S(O)(O)—NH-optionally substituted alkyl, 3-sulfamate, 4-sulfamate derivative, e.g., —O—S(O)(O)—NHR PR , —O—S(O)(O)—NHCH 3 , —O—S(O)(O)—NHC 2 H 5 , —O—S(O)(O)—NHC 3 H 7 , —O—S(O)(O)—NHC 4 H 9 , —O—S(O)(O)—N(RD) 2 or —O—S(O)(O)—NH-optionally substituted alkyl, 5-sulfonate, 6-sulfamide, 7-sulfinamide, 8 -sulfurous diamide, 9-optionally protected monosaccharide, e.g., D-, L- or DL-glucose, fructose, rhamnose or glucuronic acid, 10-optionally protected oligosaccharide, e.g., D-, L- or DL-galactose-galactose, -galactose-mannose or -glucuronic acid-glucose. In this group, the optionally protected monosaccharide and optionally protected oligomonosaccharide moieties are typically linked to the 3-position through an oxygen, sulfur or nitrogen atom.

Exemplary group 47 compounds include glycosides such as 7β-glycosides and 7α-glycosides, 3β, 17α-dihydroxyandrost-5-ene-7β-O-1′-β′-glucopyranose, 3α, 17α-dihydroxyandrost-5-ene-7β-O-1′-β′-glucopyranose, 3β-hydroxy-16α-fluoro-17-oxoandrost-5-ene-7β-O-1′-β′-glucopyranose, 3β, 17β-dihydroxyandrost-5-ene-7α-1′-β′-glucopyranose, 3α, 17β-dihydroxyandrost-5-ene-7β-O-1′-β′-glucopyranose, 3α-hydroxy-16β-fluoro-17-oxoandrost-5-ene-7α-1′-β′-glucopyranose and analogs of any of these compounds having one, two or more moieties described herein for variable groups, e.g., 16α-halo, 16β-halo, 4α-halo, 4β-halo, 4α-alkyl, 4β-alkyl, 12α-halo, 12β-halo, 12α-alkyl, 12β-alkyl, 11-dihalo, 11-alkyl, 11α-alkyl, 11-dialkyl, 12-dialkyl, 12α-hydroxyorthiol, 12β-hydroxy or thiol, 12-oxo, 12α-halo, 12β-halo, 12α-fluoro, 12β-fluoro, 12α-alkoxy, 12β-alkoxy, 2-oxa, 11-oxa, 15-oxa, 19-nor (i.e., R 6 is —H), 18-homo (i.e., R 5 is —C 2 H 5 ) or the like where any alkyl or alkoxy moieties are optionally substituted. Other exemplary moieties at R 2 include β-D-glucopyranosyl, β-D-glucopyranuronosyl, β-D-2-acetamido-2-deoxy-glucopyranosyl, β-D-galactopyranosyl, β-D-fucopyranosyl, β-L-fucopyranosyl, α-D-fructofuranosyl, β-D-fructofuranosyl, β-D-xylopyranosyl, β-L-xylopyranosyl, α-D-arabanopyranosyl, α-L-arabanopyranosyl, α-L-rhamnopyranosyl, α-D-rhamnopyranosyl, α-D-cellobiosyl, β-D-cellobiosyl, β-D-lactosyl, β-D-maltosyl, β-D-gentiobiosyl, 3-O-β-D-galactopyranosyl-α-D-arabanopyranosyl or β-D-maltotriosyl, any of which are optionally protected and where R 2 is in the α- or β-configuration.

These compounds include compounds in group 47-1 through 47-41-34-27-20-19-18-17-16-15-14-13, which collectively are group 47 compounds. These include groups 47-1, 47-2, 47-3, 47-4, 47-5, 47-5A, 47-6, 47-7, 47-8, 47-8A, 47-9, 47-10, 47-10A, 47-11, 47-12, 47-13, which are compounds in groups 1 through 13 where R 2 substituents 1-10 in Table A are replaced with the moieties given in this group. Group 47 compounds also include groups 47-14-1, 47-14-2, 47-14-3, 47-14-4, 47-14-5, 47-14-5A, 47-14-6, 47-14-7, 47-14-8, 47-14-8A, 47-14-9, 47-14-10, 47-14-10A, 47-14-11, 47-14-12 and 47-14-13, which are group 14 compounds in groups 14-1 through 14-13 where R 2 substituents 1-10 in Table A are replaced with the moieties given in this group.

Other group 47 compounds include (1) groups 47-15-1, 47-15-2, 47-15-3, 47-15-4, 47-15-5, 47-15-5A, 47-15-6, 47-15-7, 47-15-8, 47-15-8A, 47-15-9, 47-15-10, 47-15-10A, 47-15-11, 47-15-12 and 47-15-13, which are group 15 compounds in groups 15-1 through 15-13, (2) groups 47-16-1, 47-16-2, 47-16-3, 47-16-4, 47-16-5, 47-16-5A, 47-16-6, 47-16-7, 47-16-8, 47-16-8A, 47-16-9, 47-16-10, 47-16-10A, 47-16-11, 47-16-12 and 47-16-13, which are group 16 compounds in groups 16-1 through 16-13, (3) groups 47-17-1, 47-17-2, 47-17-3, 47-17-4, 47-17-5, 47-17-5A, 47-17-6, 47-17-7, 47-17-8, 47-17-8A, 47-17-9, 47-17-10, 47-17-10A, 47-17-11, 47-17-12 and 47-17-13, which are group 17 compounds in groups 17-1 through 17-13, (4) groups 47-15-14-1, 47-15-14-2, 47-15-14-3, 47-15-14-4, 47-15-14-5, 47-15-14-5A, 47-15-14-6, 47-15-14-7, 47-15-14-8, 47-15-14-8A, 47-15-14-9, 47-15-14-10, 47-15-14-10A, 47-15-14-11, 47-15-14-12 and 47-15-14-13, which are group 15 compounds in groups 15-14-1 through 15-14-13, (5) groups 47-16-14-1, 47-16-14-2, 47-16-14-3, 47-16-14-4, 47-16-14-5, 47-16-14-5A, 47-16-14-6, 47-16-14-7, 47-16-14-8, 47-16-14-8A, 47-16-14-9, 47-16-14-10, 47-16-14-10A, 47-16-14-11, 47-16-14-12 and 47-16-14-13, which are group 16 compounds in groups 16-14-1 through 16-14-13, (6) groups 47-17-14-1, 47-17-14-2, 47-17-14-3, 47-17-14-4, 47-17-14-5, 47-17-14-5A, 47-17-14-6, 47-17-14-7, 47-17-14-8, 47-17-14-8A, 47-17-14-9, 47-17-14-10, 47-17-14-10A, 47-17-14-11, 47-17-14-12, 47-17-14-13, which are group 17 compounds in groups 17-14-1 through 17-14-13, (7) groups 47-16-15-1, 47-16-15-2, 47-16-15-3, 47-16-15-4, 47-16-15-5, 47-16-15-5A, 47-16-15-6, 47-16-15-7, 47-16-15-8, 47-16-15-8A, 47-16-15-9, 47-16-15-10, 47-16-15-10A, 47-16-15-11, 47-16-15-12, 47-16-15-13, which are group 16 compounds in groups 16-15-1 through 16-15-13, (8) groups 47-17-15-1, 47-17-15-2, 47-17-15-3, 47-17-15-4, 47-17-15-5, 47-17-15-5A, 47-17-15-6, 47-17-15-7, 47-17-15-8, 47-17-15-8A, 47-17-15-9, 47-17-15-10, 47-17-15-10A, 47-17-15-11, 47-17-15-12, 47-17-15-13, which are group 17 compounds in groups 17-15-1 through 17-15-13, (9) groups 47-17-16-1, 47-17-16-2, 47-17-16-3, 47-17-16-4, 47-17-16-5, 47-17-16-5A, 47-17-16-6, 47-17-16-7, 47-17-16-8, 47-17-16-8A, 47-17-16-9, 47-17-16-10, 47-17-16-10A, 47-17-16-11, 47-17-16-12, 47-17-16-13, which are group 17 compounds in groups 17-16-1 through 17-16-13, (10) groups 47-16-15-14-1, 47-16-15-14-2, 47-16-15-14-3, 47-16-15-14-4, 47-16-15-14-5, 47-16-15-14-5A, 47-16-15-14-6, 47-16-15-14-7, 47-16-15-14-8, 47-16-15-14-8A, 47-16-15-14-9, 47-16-15-14-10, 47-16-15-14-10A, 47-16-15-14-11, 47-16-15-14-12, 47-16-15-14-13, which are group 16 compounds in groups 16-15-14-1 through 16-15-14-13, (11) groups 47-17-15-14-1, 47-17-15-14-2, 47-17-15-14-3, 47-17-15-14-4, 47-17-15-14-5, 47-17-15-14-5A, 47-17-15-14-6, 47-17-15-14-7, 47-17-15-14-8, 47-17-15-14-8A, 47-17-15-14-9, 47-17-15-14-10, 47-17-15-14-10A, 47-17-15-14-11, 47-17-15-14-12, 47-17-15-14-13, which are group 17 compounds in groups 17-15-14-1 through 17-15-14-13, (12) groups 47-17-16-14-1, 47-17-16-14-2, 47-17-16-14-3, 47-17-16-14-4, 47-17-16-14-5, 47-17-16-14-5A, 47-17-16-14-6, 47-17-16-14-7, 47-17-16-14-8, 47-17-16-14-8A, 47-17-16-14-9, 47-17-16-14-10, 47-17-16-14-10A, 47-17-16-14-11, 47-17-16-14-12, 47-17-16-14-13, which are group 17 compounds in groups 17-16-14-1 through 17-15-14-13, (13) groups 47-17-16-15-1, 47-17-16-15-2, 47-17-16-15-3, 47-17-16-15-4, 47-17-16-15-5, 47-17-16-15-5A, 47-17-16-15-6, 47-17-16-15-7, 47-17-16-15-8, 47-17-16-15-8A, 47-17-16-15-9, 47-17-16-15-10, 47-17-16-15-10A, 47-17-16-15-11, 47-17-16-15-12 and 47-17-16-15-13, which are group 17 compounds in groups 17-16-15-1 through 17-16-15-13, (14) groups 47-17-16-15-14-1, 47-17-16-15-14-2, 47-17-16-15-14-3, 47-17-16-15-14-4, 47-17-16-15-14-5, 47-17-16-15-14-5A, 47-17-16-15-14-6, 47-17-16-15-14-7, 47-17-16-15-14-8, 47-17-16-15-14-8A, 47-17-16-15-14-9, 47-17-16-15-14-10, 47-17-16-15-14-10A, 47-17-16-15-14-11, 47-17-16-15-14-12 and 47-17-16-15-14-13, which are group 17 compounds in groups 17-16-15-14-1 through 17-16-15-14-13, (15) all of the compounds and/or groups described in group 18, (16) all of the compounds and/or groups described in group 19, (17) all of the compounds and/or groups described in group 20, (18) all of the compounds and/or groups described in groups 21, 22, 23, 24, 25, 26, 26A, 26B, 26C, 26E and 27, (19) all of the compounds and/or groups described in groups 28, 29, 30, 31, 32, 33, 33A, 33B, 33C, 33D, 33E and 34 and (20) all of the compounds and/or groups described in groups 35, 36, 37, 38, 39, 40, 40A, 40B, 40C, 40D, 40E and 41.

Group 47A. This group contains compounds in groups 1-41 above where R 2 substituents 1-10 listed in Table A are replaced with the following groups: 1 —N-pyrrolidine, 2 —N1-pyrazolone, 3 —N2-pyrazolone, 4 —N-imidazolidin-2-one, 5 —N1-imidazole, 6 —N1-4,5-dihydroimidazole, 7 —N-morpholine, 8 —N1-pyridine, 9 —N-piperidine, 10 —N-piperazine.

These compounds include compounds in group 47A-1 through 47A-41-34-27-20-19-18-17-16-15-14-13, which collectively are group 47A compounds. These include groups 47A-1, 47A-2, 47A-3, 47A-4, 47A-5, 47A-5A, 47A-6, 47A-7, 47A-8, 47A-8A, 47A-9, 47A-10, 47A-10A, 47A-11, 47A-12, 47A-13, which are compounds in groups 1 through 13 where R 2 substituents 1-10 in Table A are replaced with the moieties given in this group. Group 47A compounds also include groups 47A-14-1, 47A-14-2, 47A-14-3, 47A-14-4, 47A-14-5, 47A-14-5A, 47A-14-6, 47A-14-7, 47A-14-8, 47A-14-8A, 47A-14-9, 47A-14-10, 47A-14-10A, 47A-14-11, 47A-14-12 and 47A-14-13, which are group 14 compounds in groups 14-1 through 14-13 where R 2 substituents 1-10 in Table A are replaced with the moieties given in this group.

Other group 47A compounds include (1) groups 47A-15-1, 47A-15-2, 47A-15-3, 47A-15-4, 47A-15-5, 47A-15-5A, 47A-15-6, 47A-15-7, 47A-15-8, 47A-15-8A, 47A-15-9, 47A-15-10, 47A-15-10A, 47A-15-11, 47A-15-12 and 47A-15-13, which are group 15 compounds in groups 15-1 through 15-13, (2) groups 47A-16-1, 47A-16-2, 47A-16-3, 47A-16-4, 47A-16-5, 47A-16-5A, 47A-16-6, 47A-16-7, 47A-16-8, 47A-16-8A, 47A-16-9, 47A-16-10, 47A-16-10A, 47A-16-11, 47A-16-12 and 47A-16-13, which are group 16 compounds in groups 16-1 through 16-13, (3) groups 47A-17-1, 47A-17-2, 47A-17-3, 47A-17-4, 47A-17-5, 47A-17-5A, 47A-17-6, 47A-17-7, 47A-17-8, 47A-17-8A, 47A-17-9, 47A-17-10, 47A-17-10A, 47A-17-11, 47A-17-12 and 47A-17-13, which are group 17 compounds in groups 17-1 through 17-13, (4) groups 47A-15-14-1, 47A-15-14-2, 47A-15-14-3, 47A-15-14-4, 47A-15-14-5, 47A-15-14-5A, 47A-15-14-6, 47A-15-14-7, 47A-15-14-8, 47A-15-14-8A, 47A-15-14-9, 47A-15-14-10, 47A-15-14-10A, 47A-15-14-11, 47A-15-14-12 and 47A-15-14-13, which are group 15 compounds in groups 15-14-1 through 15-14-13, (5) groups 47A-16-14-1, 47A-16-14-2, 47A-16-14-3, 47A-16-14-4, 47A-16-14-5, 47A-16-14-5A, 47A-16-14-6, 47A-16-14-7, 47A-16-14-8, 47A-16-14-8A, 47A-16-14-9, 47A-16-14-10, 47A-16-14-10A, 47A-16-14-11, 47A-16-14-12 and 47A-16-14-13, which are group 16 compounds in groups 16-14-1 through 16-14-13, (6) groups 47A-17-14-1, 47A-17-14-2, 47A-17-14-3, 47A-17-14-4, 47A-17-14-5, 47A-17-14-5A, 47A-17-14-6, 47A-17-14-7, 47A-17-14-8, 47A-17-14-8A, 47A-17-14-9, 47A-17-14-10, 47A-17-14-10A, 47A-17-14-11, 47A-17-14-12, 47A-17-14-13, which are group 17 compounds in groups 17-14-1 through 17-14-13, (7) groups 47A-16-15-1, 47A-16-15-2, 47A-16-15-3, 47A-16-15-4, 47A-16-15-5, 47A-16-15-5A, 47A-16-15-6, 47A-16-15-7, 47A-16-15-8, 47A-16-15-8A, 47A-16-15-9, 47A-16-15-10, 47A-16-15-10A, 47A-16-15-11, 47A-16-15-12, 47A-16-15-13, which are group 16 compounds in groups 16-15-1 through 16-15-13, (8) groups 47A-17-15-1, 47A-17-15-2, 47A-17-15-3, 47A-17-15-4, 47A-17-15-5, 47A-17-15-5A, 47A-17-15-6, 47A-17-15-7, 47A-17-15-8, 47A-17-15-8A, 47A-17-15-9, 47A-17-15-10, 47A-17-15-10A, 47A-17-15-11, 47A-17-15-12, 47A-17-15-13, which are group 17 compounds in groups 17-15-1 through 17-15-13, (9) groups 47A-17-16-1, 47A-17-16-2, 47A-17-16-3, 47A-17-16-4, 47A-17-16-5, 47A-17-16-5A, 47A-17-16-6, 47A-17-16-7, 47A-17-16-8, 47A-17-16-8A, 47A-17-16-9, 47A-17-16-10, 47A-17-16-10A, 47A-17-16-11, 47A-17-16-12, 47A-17-16-13, which are group 17 compounds in groups 17-16-1 through 17-16-13, (10) groups 47A-16-15-14-1, 47A-16-15-14-2, 47A-16-15-14-3, 47A-16-15-14-4, 47A-16-15-14-5, 47A-16-15-14-5A, 47A-16-15-14-6, 47A-16-15-14-7, 47A-16-15-14-8, 47A-16-15-14-8A, 47A-16-15-14-9, 47A-16-15-14-10, 47A-16-15-14-10A, 47A-16-15-14-11, 47A-16-15-14-12, 47A-16-15-14-13, which are group 16 compounds in groups 16-15-14-1 through 16-15-14-13, (11) groups 47A-17-15-14-1, 47A-17-15-14-2, 47A-17-15-14-3, 47A-17-15-14-4, 47A-17-15-14-5, 47A-17-15-14-5A, 47A-17-15-14-6, 47A-17-15-14-7, 47A-17-15-14-8, 47A-17-15-14-8A, 47A-17-15-14-9, 47A-17-15-14-10, 47A-17-15-14-10A, 47A-17-15-14-11, 47A-17-15-14-12, 47A-17-15-14-13, which are group 17 compounds in groups 17-15-14-1 through 17-15-14-13, (12) groups 47A-17-16-14-1, 47A-17-16-14-2, 47A-17-16-14-3, 47A-17-16-14-4, 47A-17-16-14-5, 47A-17-16-14-5A, 47A-17-16-14-6, 47A-17-16-14-7, 47A-17-16-14-8, 47A-17-16-14-8A, 47A-17-16-14-9, 47A-17-16-14-10, 47A-17-16-14-10A, 47A-17-16-14-11, 47A-17-16-14-12, 47A-17-16-14-13, which are group 17 compounds in groups 17-16-14-1 through 17-15-14-13, (13) groups 47A-17-16-15-1, 47A-17-16-15-2, 47A-17-16-15-3, 47A-17-16-15-4, 47A-17-16-15-5, 47A-17-16-15-5A, 47A-17-16-15-6, 47A-17-16-15-7, 47A-17-16-15-8, 47A-17-16-15-8A, 47A-17-16-15-9, 47A-17-16-15-10, 47A-17-16-15-10A, 47A-17-16-15-11, 47A-17-16-15-12 and 47A-17-16-15-13, which are group 17 compounds in groups 17-16-15-1 through 17-16-15-13, (14) groups 47A-17-16-15-14-1, 47A-17-16-15-14-2, 47A-17-16-15-14-3, 47A-17-16-15-14-4, 47A-17-16-15-14-5, 47A-17-16-15-14-5A, 47A-17-16-15-14-6, 47A-17-16-15-14-7, 47A-17-16-15-14-8, 47A-17-16-15-14-8A, 47A-17-16-15-14-9, 47A-17-16-15-14-10, 47A-17-16-15-14-10A, 47A-17-16-15-14-11, 47A-17-16-15-14-12 and 47A-17-16-15-14-13, which are group 17 compounds in groups 17-16-15-14-1 through 17-16-15-14-13, (15) all of the compounds and/or groups described in group 18, (16) all of the compounds and/or groups described in group 19, (17) all of the compounds and/or groups described in group 20, (18) all of the compounds and/or groups described in groups 21, 22, 23, 24, 25, 26, 26A, 26B, 26C, 26E and 27, (19) all of the compounds and/or groups described in groups 28, 29, 30, 31, 32, 33, 33A, 33B, 33C, 33D, 33E and 34 and (20) all of the compounds and/or groups described in groups 35, 36, 37, 38, 39, 40, 40A, 40B, 40C, 40D, 40E and 41.

Group 47B. This group contains compounds in groups 1-41 above where R 2 substituents 1-10 listed in Table A are replaced with the following groups: 1 —N-piperazine substituted at N4 with optionally substituted alkyl, 2 —N-indole, 3 —N-indoline, 4 —N-quinolidine, 5 —NH—C(O)—CH 2 —CH 2 —C(O)—OH, 6 —NH—C(O)—CH 2 —C(O)—OH, 7 —NH—C(O)—CH 2 —CH 2 —C(O)—OR PR , 8 —NH—C(O)—CH 2 —C(O)—OR PR , 9 —NH—C(O)—(CH 2 ) 3 —C(O)—OH, 10 —NH—C(O)—(CH 2 ) 3 —C(O)—OR PR . Ionizable moieties such as free carboxyl groups include salts, e.g., Na + or K + . R PR is a protecting group.

Group 47C. This group contains compounds in groups 1-41 above where R 2 substituents 1-10 listed in Table A are replaced with the following groups: 1 —NH—CH(CH 3 )—C(O)OH, 2 —NH—CH(CH 3 )—C(O)OR PR , 3 —NH—CH(CH 2 OH)—C(O)OH, 4 —NH—CH(CH 2 OH)—C(O)OR PR , 5 —NH—CH 2 —CH 2 —C(O)—OH, 6 —NH—CH 2 —C(O)—OH, 7 —NH—CH 2 —CH 2 —C(O)—OR PR , 8 —NH—CH 2 —C(O)—OR PR , 9 —NH—(CH 2 ) 3 —C(O)—OH, 10 —NH—(CH 2 ) 3 —C(O)—OR PR . Ionizable moieties such as free carboxyl groups include salts, e.g., Na + or K + . R PR is a protecting group.

Group 47D. This group contains compounds in groups 1-41 above where R 2 substituents 1-10 listed in Table A are replaced with the following groups: 1 —NH—CH(CH 3 )—C(O)OH, 2 —NH—NH—C(O)CH 3 , 3 —NH—NH—C(O)OCH 3 , 4 —NH—NH—C(O)C 2 H 5 , 5 —NH—NH—C(O)OC 2 H 5 , 6 —NH—NH—C(O)C 3 H 7 , 7 —NH—NH—C(O)-optionally substituted alkyl, 8 —NH—C(NH-optionally substituted alkyl)=N-optionally substituted alkyl, 9 —NH—C(NH—CH 3 )═N—CH 3 , 10 —NH—C(NH—C 2 H 5 )═N—C 2 H 5 .

Group 47E. This group contains compounds in groups 1-41 above where R 2 substituents 1-10 listed in Table A are replaced with the following groups: 1 spiro β-NH—(CH 2 ) 2 —O-α, 2 spiro α-NH—(CH 2 ) 2 —O-β, 3 spiro β-NH—(CH 2 ) 2 —NH-α, 4 spiro α-NH—(CH 2 ) 2 —NH-β, 5 spiro β-NH—CH═N—CH 2 -α, 6 spiro α-NH—CH═N—CH 2 -β, 7 spiro β-NH—CHR 10 —CHR 10 —O-α, 8 spiro α-NH—CHR 10 —CHR 10 —O-β, 9 spiro β-NH—CHR 10 —CHR 10 —NH-α, 10 spiro α-NH—CHR 10 —CHR 10 —NH—O—. Each R 10 is independently chosen and has the meaning given above, e.g., —H, —OH, ═O, —SH, ═S, halogen or optionally substituted alkyl.

Group 48. This group contains compounds in groups 1-41 above where R 2 substituents 1-10 listed in Table A are replaced with the following groups: 1-glycol, e.g., propylene glycol or ethylene glycol, 2-polyethylene glycol, e.g., PEG 100 or PEG 200, 3 -an acetal ring, 4-a spiro ring, 5-a thioacetal ring, 6 spiro —O—CH 2 —O—, 7 spiro —O—(CH 2 ) 2 —O—, 8 spiro —NH—(CH 2 ) 2 —O—, 9 —NH—C(O)—(CH 2 ) 2 —C(O)O—CH 3 , 10 —NH—C(O)—(CH 2 ) 2 —C(O)—OH.

Group 49. This group contains compounds in groups 1-48 above wherein R 4 is single bonded and a second R 4 that is not —H is present. The second R 4 can be a moiety defined herein for R 4 , e.g., optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, halogen, ester, —OH, —CH 3 , —C 2 H 5 , —C 3 H 7 , —CN, —C≡CH, —C≡C-halogen, —C≡C—OH, —C≡C—CH 3 , —C═CH 2 , —CH 2 —C═CH 2 , —NH 2 , —SH or —OH.

These compounds include compounds in group 49-1 through 49-48-41-34-27-20-19-18-17-16-15-14-13, which collectively are group 49 compounds. These include groups 49-1, 49-2, 49-3, 49-4, 49-5, 49-5A, 49-6, 49-7, 49-8, 49-8A, 49-9, 49-10, 49-10A, 49-11, 49-12, 49-13, which are compounds in groups 1 through 13 where a second R 4 substituent is present. Group 49 compounds also include groups 49-14-1, 49-14-2, 49-14-3, 49-14-4, 49-14-5, 49-14-5A, 49-14-6, 49-14-7, 49-14-8, 49-14-8A, 49-14-9, 49-14-10, 49-14-10A, 49-14-11, 49-14-12 and 49-14-13, which are group 14 compounds in groups 14-1 through 14-13 where a second R 4 substituent is present.

Other group 49 compounds include (1) groups 49-15-1, 49-15-2, 49-15-3, 49-15-4, 49-15-5, 49-15-5A, 49-15-6, 49-15-7, 49-15-8, 49-15-8A, 49-15-9, 49-15-10, 49-15-10A, 49-15-11, 49-15-12 and 49-15-13, which are group 15 compounds in groups 15-1 through 15-13, (2) groups 49-16-1, 49-16-2, 49-16-3, 49-16-4, 49-16-5, 49-16-5A, 49-16-6, 49-16-7, 49-16-8, 49-16-8A, 49-16-9, 49-16-10, 49-16-10A, 49-16-11, 49-16-12 and 49-16-13, which are group 16 compounds in groups 16-1 through 16-13, (3) groups 49-17-1, 49-17-2, 49-17-3, 49-17-4, 49-17-5, 49-17-5A, 49-17-6, 49-17-7, 49-17-8, 49-17-8A, 49-17-9, 49-17-10, 49-17-10A, 49-17-11, 49-17-12 and 49-17-13, which are group 17 compounds in groups 17-1 through 17-13, (4) groups 49-15-14-1, 49-15-14-2, 49-15-14-3, 49-15-14-4, 49-15-14-5, 49-15-14-5A, 49-15-14-6, 49-15-14-7, 49-15-14-8, 49-15-14-8A, 49-15-14-9, 49-15-14-10, 49-15-14-10A, 49-15-14-11, 49-15-14-12 and 49-15-14-13, which are group 15 compounds in groups 15-14-1 through 15-14-13, (5) groups 49-16-14-1, 49-16-14-2, 49-16-14-3, 49-16-14-4, 49-16-14-5, 49-16-14-5A, 49-16-14-6, 49-16-14-7, 49-16-14-8, 49-16-14-8A, 49-16-14-9, 49-16-14-10, 49-16-14-10A, 49-16-14-11, 49-16-14-12 and 49-16-14-13, which are group 16 compounds in groups 16-14-1 through 16-14-13, (6) groups 49-17-14-1, 49-17-14-2, 49-17-14-3, 49-17-14-4, 49-17-14-5, 49-17-14-5A, 49-17-14-6, 49-17-14-7, 49-17-14-8, 49-17-14-8A, 49-17-14-9, 49-17-14-10, 49-17-14-10A, 49-17-14-11, 49-17-14-12, 49-17-14-13, which are group 17 compounds in groups 17-14-1 through 17-14-13, (7) groups 49-16-15-1, 49-16-15-2, 49-16-15-3, 49-16-15-4, 49-16-15-5, 49-16-15-5A, 49-16-15-6, 49-16-15-7, 49-16-15-8, 49-16-15-8A, 49-16-15-9, 49-16-15-10, 49-16-15-10A, 49-16-15-11, 49-16-15-12, 49-16-15-13, which are group 16 compounds in groups 16-15-1 through 16-15-13, (8) groups 49-17-15-1, 49-17-15-2, 49-17-15-3, 49-17-15-4, 49-17-15-5, 49-17-15-5A, 49-17-15-6, 49-17-15-7, 49-17-15-8, 49-17-15-8A, 49-17-15-9, 49-17-15-10, 49-17-15-10A, 49-17-15-11, 49-17-15-12, 49-17-15-13, which are group 17 compounds in groups 17-15-1 through 17-15-13, (9) groups 49-17-16-1, 49-17-16-2, 49-17-16-3, 49-17-16-4, 49-17-16-5, 49-17-16-5A, 49-17-16-6, 49-17-16-7, 49-17-16-8, 49-17-16-8A, 49-17-16-9, 49-17-16-10, 49-17-16-10A, 49-17-16-11, 49-17-16-12, 49-17-16-13, which are group 17 compounds in groups 17-16-1 through 17-16-13, (10) groups 49-16-15-14-1, 49-16-15-14-2, 49-16-15-14-3, 49-16-15-14-4, 49-16-15-14-5, 49-16-15-14-5A, 49-16-15-14-6, 49-16-15-14-7, 49-16-15-14-8, 49-16-15-14-8A, 49-16-15-14-9, 49-16-15-14-10, 49-16-15-14-10A, 49-16-15-14-11, 49-16-15-14-12, 49-16-15-14-13, which are group 16 compounds in groups 16-15-14-1 through 16-15-14-13, (11) groups 49-17-15-14-1, 49-17-15-14-2, 49-17-15-14-3, 49-17-15-14-4, 49-17-15-14-5, 49-17-15-14-5A, 49-17-15-14-6, 49-17-15-14-7, 49-17-15-14-8, 49-17-15-14-8A, 49-17-15-14-9, 49-17-15-14-10, 49-17-15-14-10A, 49-17-15-14-11, 49-17-15-14-12, 49-17-15-14-13, which are group 17 compounds in groups 17-15-14-1 through 17-15-14-13, (12) groups 49-17-16-14-1, 49-17-16-14-2, 49-17-16-14-3, 49-17-16-14-4, 49-17-16-14-5, 49-17-16-14-5A, 49-17-16-14-6, 49-17-16-14-7, 49-17-16-14-8, 49-17-16-14-8A, 49-17-16-14-9, 49-17-16-14-10, 49-17-16-14-10A, 49-17-16-14-11, 49-17-16-14-12, 49-17-16-14-13, which are group 17 compounds in groups 17-16-14-1 through 17-15-14-13, (13) groups 49-17-16-15-1, 49-17-16-15-2, 49-17-16-15-3, 49-17-16-15-4, 49-17-16-15-5, 49-17-16-15-5A, 49-17-16-15-6, 49-17-16-15-7, 49-17-16-15-8, 49-17-16-15-8A, 49-17-16-15-9, 49-17-16-15-10, 49-17-16-15-10A, 49-17-16-15-11, 49-17-16-15-12 and 49-17-16-15-13, which are group 17 compounds in groups 17-16-15-1 through 17-16-15-13, (14) groups 49-17-16-15-14-1, 49-17-16-15-14-2, 49-17-16-15-14-3, 49-17-16-15-14-4, 49-17-16-15-14-5, 49-17-16-15-14-5A, 49-17-16-15-14-6, 49-17-16-15-14-7, 49-17-16-15-14-8, 49-17-16-15-14-8A, 49-17-16-15-14-9, 49-17-16-15-14-10, 49-17-16-15-14-10A, 49-17-16-15-14-11, 49-17-16-15-14-12 and 49-17-16-15-14-13, which are group 17 compounds in groups 17-16-15-14-1 through 17-16-15-14-13, (15) all of the compounds and/or groups described in group 18, (16) all of the compounds and/or groups described in group 19, (17) all of the compounds and/or groups described in group 20, (18) all of the compounds and/or groups described in groups 21, 22, 23, 24, 25, 26, 26A, 26B, 26C, 26E and 27, (19) all of the compounds and/or groups described in groups 28, 29, 30, 31, 32, 33, 33A, 33B, 33C, 33D, 33E and 34, (20) all of the compounds and/or groups described in groups 35, 36, 37, 38, 39, 40, 40A, 40B, 40C, 40D, 40E and 41 and (21) all of the compounds and/or groups described in groups 42, 43, 44, 45, 46, 47, 47A, 47B, 47C, 47D, 47E, and 48.

Group 50. This group contains compounds in groups 1-49 above wherein R 1 is single bonded and a second R 1 that is not —H is present. The second R 1 can be a moiety defined herein for R 1 , e.g., optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, halogen, ester, —OH, —CH 3 , —C 2 H 5 , —C 3 H 7 , —CN, —C≡CH, —C≡C-halogen, —C≡C—OH, —C≡C—CH 3 , —C═CH 2 , —CH 2 —C═CH 2 , —NH 2 , —SH or —OH.

These compounds include compounds in group 50-1 through 50-49-48-41-34-27-20-19-18-17-16-15-14-13, which collectively are group 50 compounds. These include groups 50-1, 50-2, 50-3, 50-4, 50-5, 50-5A, 50-6, 50-7, 50-8, 50-8A, 50-9, 50-10, 50-10A, 50-11, 50-12, 50-13, which are compounds in groups 1 through 13 where a second R 1 substituent is present. Group 50 compounds also include groups 50-14-1, 50-14-2, 50-14-3, 50-14-4, 50-14-5, 50-14-5A, 50-14-6, 50-14-7, 50-14-8, 50-14-8A, 50-14-9, 50-14-10, 50-14-10A, 50-14-11, 50-14-12 and 50-14-13, which are group 14 compounds in groups 14-1 through 14-13 where a second R 1 substituent is present.

Other group 50 compounds include (1) groups 50-15-1, 50-15-2, 50-15-3, 50-15-4, 50-15-5, 50-15-5A, 50-15-6, 50-15-7, 50-15-8, 50-15-8A, 50-15-9, 50-15-10, 50-15-10A, 50-15-11, 50-15-12 and 50-15-13, which are group 15 compounds in groups 15-1 through 15-13, (2) groups 50-16-1, 50-16-2, 50-16-3, 50-16-4, 50-16-5, 50-16-5A, 50-16-6, 50-16-7, 50-16-8, 50-16-8A, 50-16-9, 50-16-10, 50-16-10A, 50-16-11, 50-16-12 and 50-16-13, which are group 16 compounds in groups 16-1 through 16-13, (3) groups 50-17-1, 50-17-2, 50-17-3, 50-17-4, 50-17-5, 50-17-5A, 50-17-6, 50-17-7, 50-17-8, 50-17-8A, 50-17-9, 50-17-10, 50-17-10A, 50-17-11, 50-17-12 and 50-17-13, which are group 17 compounds in groups 17-1 through 17-13, (4) groups 50-15-14-1, 50-15-14-2, 50-15-14-3, 50-15-14-4, 50-15-14-5, 50-15-14-5A, 50-15-14-6, 50-15-14-7, 50-15-14-8, 50-15-14-8A, 50-15-14-9, 50-15-14-10, 50-15-14-10A, 50-15-14-11, 50-15-14-12 and 50-15-14-13, which are group 15 compounds in groups 15-14-1 through 15-14-13, (5) groups 50-16-14-1, 50-16-14-2, 50-16-14-3, 50-16-14-4, 50-16-14-5, 50-16-14-5A, 50-16-14-6, 50-16-14-7, 50-16-14-8, 50-16-14-8A, 50-16-14-9, 50-16-14-10, 50-16-14-10A, 50-16-14-11, 50-16-14-12 and 50-16-14-13, which are group 16 compounds in groups 16-14-1 through 16-14-13, (6) groups 50-17-14-1, 50-17-14-2, 50-17-14-3, 50-17-14-4, 50-17-14-5, 50-17-14-5A, 50-17-14-6, 50-17-14-7, 50-17-14-8, 50-17-14-8A, 50-17-14-9, 50-17-14-10, 50-17-14-10A, 50-17-14-11, 50-17-14-12, 50-17-14-13, which are group 17 compounds in groups 17-14-1 through 17-14-13, (7) groups 50-16-15-1, 50-16-15-2, 50-16-15-3, 50-16-15-4, 50-16-15-5, 50-16-15-5A, 50-16-15-6, 50-16-15-7, 50-16-15-8, 50-16-15-8A, 50-16-15-9, 50-16-15-10, 50-16-15-10A, 50-16-15-11, 50-16-15-12, 50-16-15-13, which are group 16 compounds in groups 16-15-1 through 16-15-13, (8) groups 50-17-15-1, 50-17-15-2, 50-17-15-3, 50-17-15-4, 50-17-15-5, 50-17-15-5A, 50-17-15-6, 50-17-15-7, 50-17-15-8, 50-17-15-8A, 50-17-15-9, 50-17-15-10, 50-17-15-10A, 50-17-15-11, 50-17-15-12, 50-17-15-13, which are group 17 compounds in groups 17-15-1 through 17-15-13, (9) groups 50-17-16-1, 50-17-16-2, 50-17-16-3, 50-17-16-4, 50-17-16-5, 50-17-16-5A, 50-17-16-6, 50-17-16-7, 50-17-16-8, 50-17-16-8A, 50-17-16-9, 50-17-16-10, 50-17-16-10A, 50-17-16-11, 50-17-16-12, 50-17-16-13, which are group 17 compounds in groups 17-16-1 through 17-16-13, (10) groups 50-16-15-14-1, 50-16-15-14-2, 50-16-15-14-3, 50-16-15-14-4, 50-16-15-14-5, 50-16-15-14-5A, 50-16-15-14-6, 50-16-15-14-7, 50-16-15-14-8, 50-16-15-14-8A, 50-16-15-14-9, 50-16-15-14-10, 50-16-15-14-10A, 50-16-15-14-11, 50-16-15-14-12, 50-16-15-14-13, which are group 16 compounds in groups 16-15-14-1 through 16-15-14-13, (11) groups 50-17-15-14-1, 50-17-15-14-2, 50-17-15-14-3, 50-17-15-14-4, 50-17-15-14-5, 50-17-15-14-5A, 50-17-15-14-6, 50-17-15-14-7, 50-17-15-14-8, 50-17-15-14-8A, 50-17-15-14-9, 50-17-15-14-10, 50-17-15-14-10A, 50-17-15-14-11, 50-17-15-14-12, 50-17-15-14-13, which are group 17 compounds in groups 17-15-14-1 through 17-15-14-13, (12) groups 50-17-16-14-1, 50-17-16-14-2, 50-17-16-14-3, 50-17-16-14-4, 50-17-16-14-5, 50-17-16-14-5A, 50-17-16-14-6, 50-17-16-14-7, 50-17-16-14-8, 50-17-16-14-8A, 50-17-16-14-9, 50-17-16-14-10, 50-17-16-14-10A, 50-17-16-14-11, 50-17-16-14-12, 50-17-16-14-13, which are group 17 compounds in groups 17-16-14-1 through 17-15-14-13, (13) groups 50-17-16-15-1, 50-17-16-15-2, 50-17-16-15-3, 50-17-16-15-4, 50-17-16-15-5, 50-17-16-15-5A, 50-17-16-15-6, 50-17-16-15-7, 50-17-16-15-8, 50-17-16-15-8A, 50-17-16-15-9, 50-17-16-15-10, 50-17-16-15-10A, 50-17-16-15-11, 50-17-16-15-12 and 50-17-16-15-13, which are group 17 compounds in groups 17-16-15-1 through 17-16-15-13, (14) groups 50-17-16-15-14-1, 50-17-16-15-14-2, 50-17-16-15-14-3, 50-17-16-15-14-4, 50-17-16-15-14-5, 50-17-16-15-14-5A, 50-17-16-15-14-6, 50-17-16-15-14-7, 50-17-16-15-14-8, 50-17-16-15-14-8A, 50-17-16-15-14-9, 50-17-16-15-14-10, 50-17-16-15-14-10A, 50-17-16-15-14-11, 50-17-16-15-14-12 and 50-17-16-15-14-13, which are group 17 compounds in groups 17-16-15-14-1 through 17-16-15-14-13, (15) all of the compounds and/or groups described in group 18, (16) all of the compounds and/or groups described in group 19, (17) all of the compounds and/or groups described in group 20, (18) all of the compounds and/or groups described in groups 21, 22, 23, 24, 25, 26, 26A, 26B, 26C, 26E and 27, (19) all of the compounds and/or groups described in groups 28, 29, 30, 31, 32, 33, 33A, 33B, 33C, 33D, 33E and 34, (20) all of the compounds and/or groups described in groups 35, 36, 37, 38, 39, 40, 40A, 40B, 40C, 40D, 40E and 41 and (21) all of the compounds and/or groups described in groups 42, 43, 44, 45, 46, 47, 47A, 47B, 47C, 47D, 47E, 48 and 49.

Group 51. This group contains compounds in groups 1-50 above wherein R 3 is single bonded and a second R 3 that is not —H is present. The second R 3 can be a moiety defined herein for R 3 , e.g., optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, halogen, ester, —OH, —CH 3 , —C 2 H 5 , —C 3 H 7 , —CN, —C≡CH, —C≡C-halogen, —C≡C—OH, —C≡C—CH 3 , —C═CH 2 , —CH 2 —C═CH 2 , —NH 2 , —SH or —OH.

These compounds include compounds in group 51-1 through 51-49-48-41-34-27-20-19-18-17-16-15-14-13, which collectively are group 51 compounds. These include groups 51-1, 51-2, 51-3, 51-4, 51-5, 51-5A, 51-6, 51-7, 51-8, 51-8A, 51-9, 51-10, 51-10A, 51-11, 51-12, 51-13, which are compounds in groups 1 through 13 where a second R 3 substituent is present. Group 51 compounds also include groups 51-14-1, 51-14-2, 51-14-3, 51-14-4, 51-14-5, 51-14-5A, 51-14-6, 51-14-7, 51-14-8, 51-14-8A, 51-14-9, 51-14-10, 51-14-10A, 51-14-11, 51-14-12 and 51-14-13, which are group 14 compounds in groups 14-1 through 14-13 where a second R 3 substituent is present.

Other group 51 compounds include (1) groups 51-15-1, 51-15-2, 51-15-3, 51-15-4, 51-15-5, 51-15-5A, 51-15-6, 51-15-7, 51-15-8, 51-15-8A, 51-15-9, 51-15-10, 51-15-10A, 51-15-11, 51-15-12 and 51-15-13, which are group 15 compounds in groups 15-1 through 15-13, (2) groups 51-16-1, 51-16-2, 51-16-3, 51-16-4, 51-16-5, 51-16-5A, 51-16-6, 51-16-7, 51-16-8, 51-16-8A, 51-16-9, 51-16-10, 51-16-10A, 51-16-11, 51-16-12 and 51-16-13, which are group 16 compounds in groups 16-1 through 16-13, (3) groups 51-17-1, 51-17-2, 51-17-3, 51-17-4, 51-17-5, 51-17-5A, 51-17-6, 51-17-7, 51-17-8, 51-17-8A, 51-17-9, 51-17-10, 51-17-10A, 51-17-11, 51-17-12 and 51-17-13, which are group 17 compounds in groups 17-1 through 17-13, (4) groups 51-15-14-1, 51-15-14-2, 51-15-14-3, 51-15-14-4, 51-15-14-5, 51-15-14-5A, 51-15-14-6, 51-15-14-7, 51-15-14-8, 51-15-14-8A, 51-15-14-9, 51-15-14-10, 51-15-14-10A, 51-15-14-11, 51-15-14-12 and 51-15-14-13, which are group 15 compounds in groups 15-14-1 through 15-14-13, (5) groups 51-16-14-1, 51-16-14-2, 51-16-14-3, 51-16-14-4, 51-16-14-5, 51-16-14-5A, 51-16-14-6, 51-16-14-7, 51-16-14-8, 51-16-14-8A, 51-16-14-9, 51-16-14-10, 51-16-14-10A, 51-16-14-11, 51-16-14-12 and 51-16-14-13, which are group 16 compounds in groups 16-14-1 through 16-14-13, (6) groups 51-17-14-1, 51-17-14-2, 51-17-14-3, 51-17-14-4, 51-17-14-5, 51-17-14-5A, 51-17-14-6, 51-17-14-7, 51-17-14-8, 51-17-14-8A, 51-17-14-9, 51-17-14-10, 51-17-14-10A, 51-17-14-11, 51-17-14-12, 51-17-14-13, which are group 17 compounds in groups 17-14-1 through 17-14-13, (7) groups 51-16-15-1, 51-16-15-2, 51-16-15-3, 51-16-15-4, 51-16-15-5, 51-16-15-5A, 51-16-15-6, 51-16-15-7, 51-16-15-8, 51-16-15-8A, 51-16-15-9, 51-16-15-10, 51-16-15-10A, 51-16-15-11, 51-16-15-12, 51-16-15-13, which are group 16 compounds in groups 16-15-1 through 16-15-13, (8) groups 51-17-15-1, 51-17-15-2, 51-17-15-3, 51-17-15-4, 51-17-15-5, 51-17-15-5A, 51-17-15-6, 51-17-15-7, 51-17-15-8, 51-17-15-8A, 51-17-15-9, 51-17-15-10, 51-17-15-10A, 51-17-15-11, 51-17-15-12, 51-17-15-13, which are group 17 compounds in groups 17-15-1 through 17-15-13, (9) groups 51-17-16-1, 51-17-16-2, 51-17-16-3, 51-17-16-4, 51-17-16-5, 51-17-16-5A, 51-17-16-6, 51-17-16-7, 51-17-16-8, 51-17-16-8A, 51-17-16-9, 51-17-16-10, 51-17-16-10A, 51-17-16-11, 51-17-16-12, 51-17-16-13, which are group 17 compounds in groups 17-16-1 through 17-16-13, (10) groups 51-16-15-14-1, 51-16-15-14-2, 51-16-15-14-3, 51-16-15-14-4, 51-16-15-14-5, 51-16-15-14-5A, 51-16-15-14-6, 51-16-15-14-7, 51-16-15-14-8, 51-16-15-14-8A, 51-16-15-14-9, 51-16-15-14-10, 51-16-15-14-10A, 51-16-15-14-11, 51-16-15-14-12, 51-16-15-14-13, which are group 16 compounds in groups 16-15-14-1 through 16-15-14-13, (11) groups 51-17-15-14-1, 51-17-15-14-2, 51-17-15-14-3, 51-17-15-14-4, 51-17-15-14-5, 51-17-15-14-5A, 51-17-15-14-6, 51-17-15-14-7, 51-17-15-14-8, 51-17-15-14-8A, 51-17-15-14-9, 51-17-15-14-10, 51-17-15-14-10A, 51-17-15-14-11, 51-17-15-14-12, 51-17-15-14-13, which are group 17 compounds in groups 17-15-14-1 through 17-15-14-13, (12) groups 51-17-16-14-1, 51-17-16-14-2, 51-17-16-14-3, 51-17-16-14-4, 51-17-16-14-5, 51-17-16-14-5A, 51-17-16-14-6, 51-17-16-14-7, 51-17-16-14-8, 51-17-16-14-8A, 51-17-16-14-9, 51-17-16-14-10, 51-17-16-14-10A, 51-17-16-14-11, 51-17-16-14-12, 51-17-16-14-13, which are group 17 compounds in groups 17-16-14-1 through 17-15-14-13, (13) groups 51-17-16-15-1, 51-17-16-15-2, 51-17-16-15-3, 51-17-16-15-4, 51-17-16-15-5, 51-17-16-15-5A, 51-17-16-15-6, 51-17-16-15-7, 51-17-16-15-8, 51-17-16-15-8A, 51-17-16-15-9, 51-17-16-15-10, 51-17-16-15-10A, 51-17-16-15-11, 51-17-16-15-12 and 51-17-16-15-13, which are group 17 compounds in groups 17-16-15-1 through 17-16-15-13, (14) groups 51-17-16-15-14-1, 51-17-16-15-14-2, 51-17-16-15-14-3, 51-17-16-15-14-4, 51-17-16-15-14-5, 51-17-16-15-14-5A, 51-17-16-15-14-6, 51-17-16-15-14-7, 51-17-16-15-14-8, 51-17-16-15-14-8A, 51-17-16-15-14-9, 51-17-16-15-14-10, 51-17-16-15-14-10A, 51-17-16-15-14-11, 51-17-16-15-14-12 and 51-17-16-15-14-13, which are group 17 compounds in groups 17-16-15-14-1 through 17-16-15-14-13, (15) all of the compounds and/or groups described in group 18, (16) all of the compounds and/or groups described in group 19, (17) all of the compounds and/or groups described in group 20, (18) all of the compounds and/or groups described in groups 21, 22, 23, 24, 25, 26, 26A, 26B, 26C, 26E and 27, (19) all of the compounds and/or groups described in groups 28, 29, 30, 31, 32, 33, 33A, 33B, 33C, 33D, 33E and 34, (20) all of the compounds and/or groups described in groups 35, 36, 37, 38, 39, 40, 40A, 40B, 40C, 40D, 40E and 41 and (21) all of the compounds and/or groups described in groups 42, 43, 44, 45, 46, 47, 47A, 47B, 47C, 47D, 47E, 48, 49 and 50.

Group 52. This group contains compounds in groups 1-51 above wherein R 2 is single bonded and a second R 2 that is not —H is present. The second R 2 can be a moiety defined herein for R 2 , e.g., optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, halogen, ester, —OH, —CH 3 , —C 2 H 5 , —C 3 H 7 , —CN, —C≡CH, —C≡C-halogen, —C≡C—OH, —C≡C—CH 3 , —C═CH 2 , —CH 2 —C═CH 2 , —NH 2 , —SH or —OH.

These compounds include compounds in group 52-1 through 52-51-49-48-41-34-27-20-19-18-17-16-15-14-13, which collectively are group 52 compounds. These include groups 52-1, 52-2, 52-3, 52-4, 52-5, 52-5A, 52-6, 52-7, 52-8, 52-8A, 52-9, 52-10, 52-10A, 52-11, 52-12, 52-13, which are compounds in groups 1 through 13 where a second R 2 substituent is present. Group 52 compounds also include groups 52-14-1, 52-14-2, 52-14-3, 52-14-4, 52-14-5, 52-14-5A, 52-14-6, 52-14-7, 52-14-8, 52-14-8A, 52-14-9, 52-14-10, 52-14-10A, 52-14-11, 52-14-12 and 52-14-13, which are group 14 compounds in groups 14-1 through 14-13 where a second R 2 substituent is present.

Other group 52 compounds include (1) groups 52-15-1, 52-15-2, 52-15-3, 52-15-4, 52-15-5, 52-15-5A, 52-15-6, 52-15-7, 52-15-8, 52-15-8A, 52-15-9, 52-15-10, 52-15-10A, 52-15-11, 52-15-12 and 52-15-13, which are group 15 compounds in groups 15-1 through 15-13, (2) groups 52-16-1, 52-16-2, 52-16-3, 52-16-4, 52-16-5, 52-16-5A, 52-16-6, 52-16-7, 52-16-8, 52-16-8A, 52-16-9, 52-16-10, 52-16-10A, 52-16-11, 52-16-12 and 52-16-13, which are group 16 compounds in groups 16-1 through 16-13, (3) groups 52-17-1, 52-17-2, 52-17-3, 52-17-4, 52-17-5, 52-17-5A, 52-17-6, 52-17-7, 52-17-8, 52-17-8A, 52-17-9, 52-17-10, 52-17-10A, 52-17-11, 52-17-12 and 52-17-13, which are group 17 compounds in groups 17-1 through 17-13, (4) groups 52-15-14-1, 52-15-14-2, 52-15-14-3, 52-15-14-4, 52-15-14-5, 52-15-14-5A, 52-15-14-6, 52-15-14-7, 52-15-14-8, 52-15-14-8A, 52-15-14-9, 52-15-14-10, 52-15-14-10A, 52-15-14-11, 52-15-14-12 and 52-15-14-13, which are group 15 compounds in groups 15-14-1 through 15-14-13, (5) groups 52-16-14-1, 52-16-14-2, 52-16-14-3, 52-16-14-4, 52-16-14-5, 52-16-14-5A, 52-16-14-6, 52-16-14-7, 52-16-14-8, 52-16-14-8A, 52-16-14-9, 52-16-14-10, 52-16-14-10A, 52-16-14-11, 52-16-14-12 and 52-16-14-13, which are group 16 compounds in groups 16-14-1 through 16-14-13, (6) groups 52-17-14-1, 52-17-14-2, 52-17-14-3, 52-17-14-4, 52-17-14-5, 52-17-14-5A, 52-17-14-6, 52-17-14-7, 52-17-14-8, 52-17-14-8A, 52-17-14-9, 52-17-14-10, 52-17-14-10A, 52-17-14-11, 52-17-14-12, 52-17-14-13, which are group 17 compounds in groups 17-14-1 through 17-14-13, (7) groups 52-16-15-1, 52-16-15-2, 52-16-15-3, 52-16-15-4, 52-16-15-5, 52-16-15-5A, 52-16-15-6, 52-16-15-7, 52-16-15-8, 52-16-15-8A, 52-16-15-9, 52-16-15-10, 52-16-15-10A, 52-16-15-11, 52-16-15-12, 52-16-15-13, which are group 16 compounds in groups 16-15-1 through 16-15-13, (8) groups 52-17-15-1, 52-17-15-2, 52-17-15-3, 52-17-15-4, 52-17-15-5, 52-17-15-5A, 52-17-15-6, 52-17-15-7, 52-17-15-8, 52-17-15-8A, 52-17-15-9, 52-17-15-10, 52-17-15-10A, 52-17-15-11, 52-17-15-12, 52-17-15-13, which are group 17 compounds in groups 17-15-1 through 17-15-13, (9) groups 52-17-16-1, 52-17-16-2, 52-17-16-3, 52-17-16-4, 52-17-16-5, 52-17-16-5A, 52-17-16-6, 52-17-16-7, 52-17-16-8, 52-17-16-8A, 52-17-16-9, 52-17-16-10, 52-17-16-10A, 52-17-16-11, 52-17-16-12, 52-17-16-13, which are group 17 compounds in groups 17-16-1 through 17-16-13, (10) groups 52-16-15-14-1, 52-16-15-14-2, 52-16-15-14-3, 52-16-15-14-4, 52-16-15-14-5, 52-16-15-14-5A, 52-16-15-14-6, 52-16-15-14-7, 52-16-15-14-8, 52-16-15-14-8A, 52-16-15-14-9, 52-16-15-14-10, 52-16-15-14-10A, 52-16-15-14-11, 52-16-15-14-12, 52-16-15-14-13, which are group 16 compounds in groups 16-15-14-1 through 16-15-14-13, (11) groups 52-17-15-14-1, 52-17-15-14-2, 52-17-15-14-3, 52-17-15-14-4, 52-17-15-14-5, 52-17-15-14-5A, 52-17-15-14-6, 52-17-15-14-7, 52-17-15-14-8, 52-17-15-14-8A, 52-17-15-14-9, 52-17-15-14-10, 52-17-15-14-10A, 52-17-15-14-11, 52-17-15-14-12, 52-17-15-14-13, which are group 17 compounds in groups 17-15-14-1 through 17-15-14-13, (12) groups 52-17-16-14-1, 52-17-16-14-2, 52-17-16-14-3, 52-17-16-14-4, 52-17-16-14-5, 52-17-16-14-5A, 52-17-16-14-6, 52-17-16-14-7, 52-17-16-14-8, 52-17-16-14-8A, 52-17-16-14-9, 52-17-16-14-10, 52-17-16-14-10A, 52-17-16-14-11, 52-17-16-14-12, 52-17-16-14-13, which are group 17 compounds in groups 17-16-14-1 through 17-15-14-13, (13) groups 52-17-16-15-1, 52-17-16-15-2, 52-17-16-15-3, 52-17-16-15-4, 52-17-16-15-5, 52-17-16-15-5A, 52-17-16-15-6, 52-17-16-15-7, 52-17-16-15-8, 52-17-16-15-8A, 52-17-16-15-9, 52-17-16-15-10, 52-17-16-15-10A, 52-17-16-15-11, 52-17-16-15-12 and 52-17-16-15-13, which are group 17 compounds in groups 17-16-15-1 through 17-16-15-13, (14) groups 52-17-16-15-14-1, 52-17-16-15-14-2, 52-17-16-15-14-3, 52-17-16-15-14-4, 52-17-16-15-14-5, 52-17-16-15-14-5A, 52-17-16-15-14-6, 52-17-16-15-14-7, 52-17-16-15-14-8, 52-17-16-15-14-8A, 52-17-16-15-14-9, 52-17-16-15-14-10, 52-17-16-15-14-10A, 52-17-16-15-14-11, 52-17-16-15-14-12 and 52-17-16-15-14-13, which are group 17 compounds in groups 17-16-15-14-1 through 17-16-15-14-13, (15) all of the compounds and/or groups described in group 18, (16) all of the compounds and/or groups described in group 19, (17) all of the compounds and/or groups described in group 20, (18) all of the compounds and/or groups described in groups 21, 22, 23, 24, 25, 26, 26A, 26B, 26C, 26E and 27, (19) all of the compounds and/or groups described in groups 28, 29, 30, 31, 32, 33, 33A, 33B, 33C, 33D, 33E and 34, (20) all of the compounds and/or groups described in groups 35, 36, 37, 38, 39, 40, 40A, 40B, 40C, 40D, 40E and 41 and (21) all of the compounds and/or groups described in groups 42, 43, 44, 45, 46, 47, 47A, 47B, 47C, 47D, 47E, 48, 49, 50 and 51.

As is apparent from the foregoing description of F1Cs in groups 1 through 52, compound groups 14 through 52 contain a number of defined subgroups, e.g., group 14-3 is a subgroup as described for group 14 compounds where R 1 , R 2 , R 3 and R 4 can be in the configurations described in group 14, e.g., α,β,α,β, α,α,α,β, β,β,β,β, β,β,β,α or β,β,α,α respectively. Similarly, group 49 includes subgroups such as 49-18-17-14-3, 49-18-17-14-4, 49-18-17-14-5, 49-18-17-14-5A, 49-18-17-14-6, 49-18-17-14-7 and 49-18-17-14-9, which are subgroups where R 9 is substituted, e.g., R 9 is —O— or a moiety described in group 18, and such subgroups, although not specifically named or described, are expressly included in group 49. The F1C therefore include all possible subgroups in each group, regardless of whether each subgroup is specifically named or described in a given group or not. For example, groups such as 22, 23, 26, 26B, 26C, 26D and 26E, all include subgroups analogous to those described in group 26A and additional subgroups that are not expressly described, e.g., subgroups such as 26-18-1, 26-18-2, 26-18-3, 26-18-4, 26-18-5, 26-18-5A, 26-18-6, 26-18-14-1, 26-18-14-2, 26-18-14-3, 26-18-14-4, 26-18-14-5, 26-18-14-5A and 26-18-14-6 are not described expressly in group 26 above, but are included in group 26. Similarly, groups 29, 30, 33, 33B, 33C, 33D and 33E, all include subgroups analogous to those described in group 33A, while groups 36, 37, 40B, 40C, 40D, 40E and 41 all include subgroups analogous to those described in group 40A and groups 47B, 47C, 47D, 47E and 48 all include subgroups analogous to those described in group 47A. Thus, subgroups such as 33-18-3 and 33-18-14-3, which are not described expressly in group 33 above, are included in group 33.

As is apparent from the definitions provided herein, the F1Cs also include analogs of the compounds in groups 1 through 52. Exemplary analogs include compounds where R 10G and/or R 10H is a moiety other than hydrogen, e.g., halogen or optionally substituted alkyl such as —F, —Cl, —Br, —I, —CH 3 , —OH, —NH 2 or —SH. Thus, for any of the compounds or genera of compounds in groups 1 through 52, R 10G can be —F or —Cl in the α- or β-configuration. Similarly, in groups 1 through 52, R 10H can be —F, —NH 2 or —OH in the α- or β-configuration or an epoxide or cyclopropyl ring with R 7 α- or β-configuration.

Metabolites. The invention includes the therapeutic or other uses disclosed herein of metabolites of F1C, which include biologically active metabolites. Metabolites can arise from in vivo or in vitro metabolism. Metabolites of F1C include products that are new. Metabolites may result for example from the oxidation, reduction, hydrolysis, amidation, esterification, glycosidation and the like of the administered formula 1 compound, due to enzymatic or chemical processes. Metabolites may be generated in vivo in a subject or they may arise ex vivo from cells or tissues, e.g., from a mammal such as a human, rodent or a primate. Accordingly, the invention includes new F1Cs produced by a process comprising contacting an F1C with a subject or a subject's cells or tissue for a period of time sufficient to yield detectable amounts of a metabolic product thereof. Such products typically are identified by preparing a radiolabeled or mass labeled F1C that comprises, e.g., 1, 2, 3 or more 13 C, 14 C, 3 H, 2 H, 131 I, 32 P, 35 S or 99 Tc atoms bonded to the compound, and administering it as a trace labeled compound along with the unlabeled compound. The labeled and unlabeled compounds are administered by any suitable route (by, e.g., a buccal, sublingual, parenteral, topical or oral route) in a detectable dose (e.g. greater than about 0.1 μg/kg, or at least about 10 μg/kg or at least about 0.5 mg/kg of the labeled compound) to a subject, e.g., an animal or mammal such as rat, mouse, guinea pig, primate, or to a human. After administration sufficient time is allowed for metabolism to occur (typically about 30 seconds to 30 hours) and conversion products are isolated from one or more of the urine, blood, plasma, feces or other suitable biological sources. The amount of labeled formula 1 compound that is administered to a subject will vary with the specific activity of the labeled compound. Exemplary metabolic conversions of formula 1 compounds include modification of hydrogen atoms or other moieties that are bonded to, e.g., one or more of the 1, 2, 3, 4, 6, 7, 11, 15, 16 or 17 positions. Exemplary conversions at these one or more of positions include hydroxylation of ring atoms, e.g., ring carbon atoms, conjugation of hydroxyl groups that are bonded to one or more of those positions with moieties such as sulfate, phosphate or a monosaccharide or disaccharide such as glucuronic acid and hydrolysis of moieties such as esters or alkoxy groups.

Analytical characterization and reference standards. Individual F1Cs described or disclosed herein are suitable for use as standards for determining chemical or physical properties using one, two or more analytical methods, e.g., for use in HPLC, reverse phase HPLC, MS (mass spectrometry), quadrupole MS, GC-MS, LC-MS, NMR (nuclear magnetic resonance spectrometry), 2 H-NMR, 3 H-NMR, 13 C-NMR, 14 C-NMR, infrared spectrometry (IR), Fourier transform-IR, optical rotary dispersion, loss on drying for water and solvent measurement, Karl Fisher titration for water determination, differential scanning calorimetry, melting point, density, refractive index, solubility characteristics in organic solvents, aqueous systems or aqueous-organic solvent mixtures, the partition coefficient in immiscible solvent systems, e.g., octanol:water partition coefficient, heat stability or epimerization rate or characteristics of a given enantiomer. These analytical or chemical properties of each F1C are collectively referred to as analytical characteristics. For general methods, see, e.g., H. L. J. Makin et al., eds. Steroid Analysis 1995, Chapman & Hall, ISBN 0751401285. Thus, to aid in the determination of, e.g., the structure of a metabolite of a F1C or a structurally related compound, the parent compound or another structurally related F1C could be used as a standard. Metabolism of F1Cs will often include one or more of oxidation, reduction, hydroxylation or conjugation, e.g., oxidation or reduction to a —OH or ═O moiety, or conjugation with a moiety such as sulfate, phosphate, amino acid, dipeptide or a monosaccharide such as glucuronic acid at, e.g., the 2, 3, 6, 7, 11, 15, 16, 17 or other positions on the steroid nucleus. In these embodiments, the appropriate use of a F1C of known structure as a standard can aid in or verify the identification of metabolites that are projected to have closely related structures. Information regarding the identification can be useful or sometimes is necessary for, e.g., obtaining regulatory approval to market a therapeutic agent such as a F1C or understanding the potential biological role that a F1C or its metabolite can play in one of the applications disclosed herein or in a cited reference. To facilitate such uses, the F1C may be labeled as appropriate, e.g., using a F1C with, e.g., one or more 2 H, 3 H, 13 C, 14 C, 15 N, 18 O, 18 F, 35 S, 32 P or 123 I, at 1, 2 or more of the 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22 or other positions in any formula 1 steroid. Radiolabel or heavy isotope atoms may be directly bonded to, or for carbon atoms, replace a steroid nucleus atom, or they may be bonded through one, two or more intervening atoms, e.g., steroid-O— 32 P(O)(OH)(OH). Suitably labeled compounds include any of the F1Cs disclosed herein. Such labeled compounds may comprise, e.g., a 13 C at the 18 or 19 positions and 1, 2, 3 or 4 3 H may be bonded to the 13 C atom(s) or to a ring carbon(s). Other formula 1 compounds may comprise one or two 2 H or 3 H atoms bonded to one or more of the 1, 2, 4, 5, 6, 11 or 12 positions and optionally a 13 C at the 18 or 19 position(s). F1Cs and their metabolites are isolated or characterized using radiolabeled or mass labeled atoms. F1Cs are also optionally isolated by the use of antibodies capable of binding to epitopes in F1Cs or in metabolites.

In general, analysis of F1C metabolites is accomplished in the same way as conventional drug metabolism studies, which are known to those skilled in the art. The conversion products, especially when they are not otherwise found in vivo, are useful in diagnostic assays for therapeutic dosing of the formula 1 compounds even if they possess only limited therapeutic activity of their own.

Embodiments include a method (the “characterization method”) to characterize or at least partially characterize a formula 1 compound that is at least partially uncharacterized for one or more given chemical or analytical properties, e.g., a known or potential metabolite of a parent formula 1 compound, comprising (a) providing a formula 1 compound having one, two or more known characteristics, e.g., a known or at least partially known or characterized chemical structure, XRD spectrum or melting point (a “CF1C”), and a formula 1 compound that is unknown or at least partially uncharacterized, i.e., is uncharacterized for at least one of the same analytical characteristics (a “UCF1C”), (b) obtaining one, two or more analytical characteristics of the UCF1C, and (c) comparing the 1, 2 or more analytical characteristics of the CF1C with the analytical characteristics of the UCF1C. The steps in this method may be conducted in any suitable order, e.g., analytical or chemical data for the CF1C will usually be obtained before or at about the same time as one obtains the analytical or chemical data for the UCF1C. Usually the CF1C will be more completely characterized than the UCF1C, particularly with regard to its chemical structure or its relative degree of purity or with regard to the analytical or chemical data that is being sought. This method allows further characterization of the UCF1C, e.g., by confirming the UCF1C's chemical structure or by determining the UCF1C's stability under various storage or temperature conditions or in various formulations or by determining other analytical or chemical properties of interest. In this method, the CF1C itself may not be completely characterized, however, for the one, two or more analytical characteristics of interest, the CF1C will usually have a known or confirmed property or properties, while the UCF1C is unknown or at least unconfirmed for the same property or properties.

In some embodiments the characterization method is conducted by comparing dissimilar analytical characteristics. For example, the CF1C may be well characterized by GC-MS or by NMR, while an insufficient amount of the UCF1C is available for analysis with the same technique. In these cases, one can then, e.g., compare the GC-MS of the CF1C with the NMR of the UCF1C to obtain the same or essentially the same information for the UCF1C. Other examples of where this can be done is where DSC data is available for the CF1C, and only melting point data is available for the UCF1C. In this case, the CF1C DSC data is compared to the UCF1C's melting point data. Also, in conducting the characterization method, one can optionally derivatize or chemically modify the CF1C and/or the UCF1C to facilitate analysis of the compound(s). For example, in conducting MS, GC-MS or NMR analysis, one or more free hydroxyl or ketone moieties on the CF1C and/or the F2C can be silylated using, e.g., trimethylsilyl chloride, t-butyl-dimethylsilyl chloride or other suitable silylating agents. Similarly, the UCF1C may be treated or incubated with a cell line or tissue or with a glucuronidase, sulfatase, phosphatase, esterase, lipase, oxidoreductase or other enzyme and then characterized. This treatment may in some cases convert the UCF1C into the CF1C, but this conversion would usually be confirmed by one, two or more suitable analytical methods. Such treatments will usually generate additional data about the structure, properties or origin of the UCF1C.

Embodiments include modifications of the characterization method that use a CF1C and a second formula 1 compound that is believed or known to have a related structure or empirical formula. In these modifications, the CF1C is used as described and a second formula 1 compound or a UCF1C that is believed or known to be, e.g., an epimer or a salt, of the CF1C is compared to the CF1C. Invention embodiments include other modifications of the characterization method such as (1) comparing analytical or chemical data from a single CF1C with 2, 3, 4 or more UCF1C, (2) comparing analytical or chemical data from 2, 3, 4 or more CF1C with a single UCF1C and (3) comparing analytical or chemical data from 2, 3, 4 or more CF1C with 2, 3, 4 or more UCF1C. In these modifications, the CF1C or UCF1C are used essentially as described for the characterization method, except that data is obtained for the added formula 1 compounds.

Typically, when the 1, 2 or more analytical characteristics of a CF1C or a UCF1C are obtained, which may be for use in the characterization method or for other purposes, each compound is analyzed under the same or essentially the same analytical conditions using the same or essentially the same analytical technique or instrument. Variations in an analytical technique may be used where the properties of a CF1C or a UCF1C require slightly different handling or specimen preparation. An example of a variation in analytical conditions is the comparison of a property of a CF1C, e.g., its stability to heat, humidity or prolonged storage at a given temperature, with the same property of the CF1C in a composition containing an excipient(s) or in a formulation (where the CF1C in a composition is then considered the UCF1C for the characterization method). This allows the determination of the stability of the CF1C as a pure compound compared to its stability in any desired composition.

When characterizing a CF1C by MS, particularly by GC-MS, one will usually conduct an initial characterization of a formula 1 compound or a CF1C in the characterization method using a known GC-MS method (e.g., H. L. J. Makin et al., Mass Spectra and GC Data of Steroids: Androgens and Estrogens 1999 John Wiley & Sons, pages XIII-XIV) or a suitable variation of this method. For F1Cs that contain free hydroxyls or oxo groups, the hydroxyl groups can be derivatized to an ester such as acetate, hydroxyl and oxo or groups can be derivatized to trimethylsilyl ether, i.e., —O—Si(CH 3 ) 3 , and oxo groups can be derivatized to a an oxime such as ═N—O—CH 3 before GC-MS analysis. Other functional groups can also be suitably derivatized. For embodiments of the characterization method that use a GC-MS analysis method, the CF1C or the UCF1C is analyzed by the GC-MS method or a suitable variation to obtain or to confirm chemical structure information about the CF1C or the UCF1C. Suitable variations include, e.g., a change in the carrier gas from helium to hydrogen to increase the sensitivity of detection or a decrease in the ionization from 70 eV to 50 eV can give a better parent mass ion.

As is apparent from the present disclosure, the F1C may be prepared synthetically and typical embodiments will utilize purified a F1C. Purified F1C can be free, essentially free or partially free, of other F1C or other compounds such as excipients. Thus, any given purified F1C can be present as a solid that contains, e.g., less than about 15% w/w or less than about 10% w/w or less than about 8% w/w or less than about 5% w/w or less than about 3% w/w or less than about 1% w/w of one, two or more other F1Cs, excipients, synthetic by-products, decomposition products or synthesis or purification reactants or reagents. Similarly, the F1C can be present in a solution or suspension that contains at least about 90% w/w or at least about 95% w/w or at least about 97% w/w of the F1C and one or more excipients and less than about 10% or 8% or 5% or 3% w/w or 1% w/w of one, two or more other F1Cs, excipients, synthetic by-products, decomposition products or synthesis or purification reactants or reagents.

Various groups that F1Cs contain as described herein, e.g., hydroxyl groups or ketones bonded to the steroid nucleus, or substituted alkyl groups, substituted heterocycles, amino acids and peptides, which can contain one or more reactive moieties such as hydroxyl, oxo, carboxyl, amino or thiol moieties. Intermediates used to make F1Cs may be protected as is apparent in the art, e.g., using suitable R PR moieties. Noncyclic and cyclic protecting groups and corresponding cleavage reactions are described in “Protective Groups in Organic Chemistry”, Theodora W. Greene (John Wiley & Sons, Inc., New York, 1991, ISBN 0-471-62301-6) (hereafter “Greene”) and will not be detailed here.

In the context of the present invention, these protecting groups are groups that can be removed from a F1C without irreversibly changing the covalent bond structure or oxidation/reduction state of the remainder of the molecule. For example, the protecting group, —R PR , that is bonded to an —OR PR or —NHR PR group can be removed to form —OH or —NH 2 , respectively, without affecting other covalent bonds in the molecule. Protecting groups for carbonyl or ketone moieties include ethylene ketals, e.g., —O—CH 2 —CH 2 —O—. At times, when desired, more than one protecting group can be removed at a time, or they can be removed sequentially. In F1Cs containing more than one protecting group, the protecting groups are the same or different.

Protecting groups are removed by known procedures, although it will be understood that the protected intermediates fall within the scope of this invention. The removal of the protecting group may be arduous or straightforward, depending upon the economics and nature of the conversions involved. In general, one will use a protecting group with exocyclic amines or with carboxyl groups during synthesis of a F1C. For most therapeutic applications amine groups should be deprotected. Protecting groups commonly are employed to protect against covalent modification of a sensitive group in reactions such as alkylation or acylation. Ordinarily, protecting groups are removed by, e.g. hydrolysis, elimination or aminolysis. Thus, simple functional considerations will suffice to guide the selection of a reversible or an irreversible protecting group at a given locus on the F1Cs. Suitable protecting groups and criteria for their selection are described in T. W. Greene and P. G. M. Wuts, Eds. “Protective Groups in Organic Synthesis” 2nd edition, Wiley Press, at pps. 10-142, 143-174, 175-223, 224-276, 277-308, 309-405 and 406-454.

Characterization of a protecting group is made in the conventional manner, e.g., as described by Kocienski, Philip J.; “ Protecting Groups ” (Georg Thieme Verlag Stuttgart, N.Y., 1994) (hereafter “Kocienski”), Section 1.1, page 2, and Greene Chapter 1, pages 1-9. In particular, a group is a protecting group if when, based on mole ratio, 90% of that protecting group has been removed by a deprotection reaction, no more than 50%, typically 25%, more typically 10%, of the deprotected product molecules have undergone changes to their covalent bond structure or oxidation/reduction state other than those occasioned by the removal of the protecting group. When multiple protecting groups of the same type are present in the molecule, the mole ratios are determined when all of the groups of that type are removed. When multiple protecting groups of different types are present in the molecule, each type of protecting group is treated (and the mole ratios are determined) independently or together with others depending on whether the deprotection reaction conditions pertinent to one type are also pertinent to the other types present. In one embodiment, a group is a protecting group if when, based on mole ratio determined by conventional techniques, 90% of that protecting group has been removed by a conventional deprotection reaction, no more than 50%, typically 25%, more typically 10%, of the deprotected product molecules have undergone irreversible changes to their covalent bond structure or oxidation/reduction state other than those occasioned by the removal of the protecting group. Irreversible changes require chemical reactions (beyond those resulting from aqueous hydrolysis, acid/base neutralization or conventional separation, isolation or purification) to restore the covalent bond structure or oxidation/reduction state of the deprotected F1C.

Protecting groups are also described in detail together with general concepts and specific strategies for their use in Kocienski, Philip J.; “Protecting Groups” (Georg Thieme Verlag Stuttgart, N.Y., 1994), which is incorporated by reference in its entirety herein. In particular Chapter 1, Protecting Groups: An Overview, pages 1-20, Chapter 2, Hydroxyl Protecting Groups, pages 21-94, Chapter 3, Diol Protecting Groups, pages 95-117, Chapter 4, Carboxyl Protecting Groups, pages 118-154, Chapter 5, Carbonyl Protecting Groups, pages 155-184, Chapter 6, Amino Protecting Groups, pages 185-243, Chapter 7, Epilog, pages 244-252, and Index, pages 253-260, are incorporated with specificity in the context of their contents. More particularly, Sections 2.3 Silyl Ethers, 2.4 Alkyl Ethers, 2.5 Alkoxyalkyl Ethers (Acetals), 2.6 Reviews (hydroxy and thiol protecting groups), 3.2 Acetals, 3.3 Silylene Derivatives, 3.4 1,1,3,3-Tetraisopropyldisiloxanylidene Derivatives, 3.5 Reviews (diol protecting groups), 4.2 Esters, 4.3 2,6,7-Trioxabicyclo[2.2.2]octanes [OBO] and Other Ortho Esters, 4.4 Oxazolines, 4.5 Reviews (carboxyl protecting groups), 5.2 O,O-Acetals, 5.3 S,S-Acetals, 5.4 O,S-Acetals, 5.5 Reviews (carbonyl protecting groups), 6.2 N-Acyl Derivatives, 6.3 N-Sulfonyl Derivatives, 6.4 N-Sulfenyl Derivatives, 6.5 N-Alkyl Derivatives, 6.6 N-Silyl Derivatives, 6.7 Imine Derivatives, and 6.8 Reviews (amino protecting groups), are each incorporated with specificity where protection/deprotection of the requisite functionalities is discussed. Further still, the tables “Index to the Principal Protecting Groups” appearing on the inside front cover and facing page, “Abbreviations” at page xiv, and “reagents and Solvents” at page xv are each incorporated in their entirety herein at this location.

Typical hydroxy protecting groups are described in Greene at pages 14-118 and include Ethers (Methyl); Substituted Methyl Ethers (Methoxymethyl, Methylthiomethyl, t-Butylthiomethyl, (Phenyldimethylsilyl)methoxymethyl, Benzyloxymethyl, p-Methoxybenzyloxymethyl, (4-Methoxyphenoxy)methyl, Guaiacolmethyl, t-Butoxymethyl, 4-Pentenyloxymethyl, Siloxymethyl, 2-Methoxyethoxymethyl, 2,2,2-Trichloroethoxymethyl, Bis(2-chloroethoxy)methyl, 2-(Trimethylsilyl)ethoxymethyl, Tetrahydropyranyl, 3-Bromotetrahydropyranyl, Tetrahydropthiopyranyl, 1-Methoxycyclohexyl, 4-methoxytetrahydropyranyl, 1,4-Dioxan-2-yl, Tetrahydrofuranyl, Tetrahydrothiofuranyl); Substituted Ethyl Ethers (1-Ethoxyethyl, 1-(2-Chloroethoxy)ethyl, 1-Methyl-1-methoxyethyl, 1-Methyl-1-benzyloxyethyl, 1-Methyl-1-benzyloxy-2-fluoroethyl, 2,2,2-Trichloroethyl, 2-Trimethylsilylethyl, 2-(Phenylselenyl)ethyl, t-Butyl, Allyl, p-Chlorophenyl, p-Methoxyphenyl, 2,4-Dinitrophenyl, Benzyl); Substituted Benzyl Ethers (p-Methoxybenzyl, 3,4-Dimethoxybenzyl, o-Nitrobenzyl, p-Nitrobenzyl, p-Halobenzyl, 2,6-Dichlorobenzyl, p-Cyanobenzyl,p-Phenylbenzyl, 2- and 4-Picolyl, 3-Methyl-2-picolyl N-Oxido, Diphenylmethyl, p,p′-Dinitrobenzhydryl, 5-Dibenzosuberyl, Triphenylmethyl, 1,3-Benzodithiolan-2-yl, Benzisothiazolyl, S,S-Dioxido); Silyl Ethers (Trimethylsilyl, Triethylsilyl, Triisopropylsilyl, Dimethylisopropylsilyl, Diethylisopropylsily, Dimethylthexylsilyl, t-Butyldimethylsilyl, t-Butyldiphenylsilyl, Tribenzylsilyl, Tri-p-xylylsilyl, Triphenylsilyl, Diphenylmethylsilyl, t-Butylmethoxyphenylsilyl); Esters (Formate, Benzoylformate, Acetate, Choroacetate, Dichloroacetate, Trichloroacetate, Trifluoroacetate, Methoxyacetate; Carbonates (Methyl, 9-Fluorenylmethyl, Ethyl, 2,2,2-Trichloroethyl, 2-(Trimethylsilyl)ethyl, 2-(Phenylsulfonyl)ethyl, 2-(Triphenylphosphonio)ethyl, Isobutyl, Vinyl, Allyl, p-Nitrophenyl, Benzyl, p-Methoxybenzyl, 3,4-Dimethoxybenzyl, o-Nitrobenzyl, p-Nitrobenzyl); Groups With Assisted Cleavage (2-Iodobenzoate, 4-Azidobutyrate, 4-Nitro-4-methyl pentanoate, o-(Dibromomethyl)benzoate, 2-Formylbenzenesulfonate, 2-(Methylthiomethoxy)ethyl Carbonate, 4-(Methylthiomethoxy)butyrate, 2-(Methylthiomethoxymethyl)benzoate); Other Esters (2,6-Dichloro-4-methylphenoxyacetate, 2,6-Dichloro-4-(1,1,3,3-tetramethyl-butyl)phenoxyacetate, Isobutyrate, Monosuccinoate, (E)-2-Methyl-2-butenoate (Tigloate), o-(Methoxycarbonyl)benzoate, p-poly-Benzoate, α-Naphthoate, Nitrate, Alkyl N,N,N′,N′-Tetramethylphosphorodiamidate, N-Phenylcarbamate, Borate, Dimethylphosphinothioyl, 2,4-Dinitro-phenylsulfenate); and Sulfonates (Sulfate, Methanesulfonate (Mesylate), Benzylsulfonate, Tosylate (Tos)). More typically hydroxy protecting groups include substituted methyl ethers, substituted benzyl ethers, silyl ethers, and esters including sulfonic acid esters, still more typically, esters, trialkylsilyl ethers and tosylates, such as acetates, trimethylsilyl and methoxymethyl.

Typical 1,2- and 1,3-diol protecting groups are described in Greene at pages 118-142 and include Cyclic Acetals and Ketals (Methylene, Ethylidene, 1-t-Butylethylidene, 1-Phenylethylidene, (4-Methoxyphenyl)ethylidene, 2,2,2-Trichloroethylidene, Acetonide (Isopropylidene), Cyclopentylidene, Cyclohexylidene, Cycloheptylidene, Benzylidene, p-Methoxybenzylidene, 2,4-Dimethoxybenzylidene, 3,4-Dimethoxybenzylidene, 2-Nitrobenzylidene); Cyclic Ortho Esters (Methoxymethylene, Ethoxymethylene, Dimethoxymethylene, 1-Methoxyethylidene, 1-Ethoxyethylidine, 1,2-Dimethoxyethylidene, alpha-Methoxybenzylidene, 1-(N,N-Dimethylamino)ethylidene Derivative, alpha-(N,N-Dimethylamino)benzylidene Derivative, 2-Oxacyclopentylidene); and Silyl Derivatives (Di-t-butylsilylene Group, 1,3-(1,1,3,3-Tetraiso-propyldisiloxanylidene) Derivative, Tetra-t-butoxydisiloxane-1,3-diylidene Derivative, Cyclic Carbonates, Cyclic Boronates, Ethyl Boronate, Phenyl Boronate). More typically, 1,2- and 1,3-diol protecting groups include epoxides and acetonides.

Typical amino protecting groups are described in Greene at pages 315-385 and include Carbamates (Methyl and Ethyl, 9-Fluorenylmethyl, 9(2-Sulfo)fluoroenylmethyl, 9-(2,7-Dibromo)fluorenylmethyl, 2,7-Di-t-buthyl-[9-(10,10-dioxo-10,10,10,10-tetrahydrothioxanthyl)]-methyl, 4-Methoxy-phenacyl); Substituted Ethyl (2,2,2-Trichoroethyl, 2-Trimethylsilylethyl, 2-Phenylethyl, 1-(1-Adamantyl)-1-methylethyl, 1,1-Dimethyl-2-haloethyl, 1,1-Dimethyl-2,2-dibromoethyl, 1,1-Dimethyl-2,2,2-trichloroethyl, 1-Methyl-1-(4-biphenylyl)ethyl, 1-(3,5-Di-t-butylphenyl)-1-methylethyl, 2-(2′- and 4′-Pyridyl)ethyl, 2-(N,N-Dicyclohexylcarboxamido)ethyl, t-Butyl, 1-Adamantyl, Vinyl, Allyl, 1-Isopropylallyl, Cinnamyl, 4-Nitrocinnamyl, 8-Quinolyl, N-Hydroxypiperidinyl, Alkyldithio, Benzyl, p-Methoxybenzyl, p-Nitrobenzyl, p-Bromobenzyl, p-Chorobenzyl, 2,4-Dichlorobenzyl, 4-Methylsulfinylbenzyl, 9-Anthrylmethyl, Diphenylmethyl); Groups With Assisted Cleavage (2-Methylthioethyl, 2-Methylsulfonylethyl, 2-(p-Toluenesulfonyl)ethyl, [2-(1,3-Dithianyl)]methyl, 4-Methylthiophenyl, 2,4-Dimethylthiophenyl, 2-Phosphonioethyl, 2-Triphenylphosphonioisopropyl, 1,1-Dimethyl-2-cyanoethyl, m-Choro-p-acyloxybenzyl, p-(Dihydroxyboryl)benzyl, 5-Benzisoxazolylmethyl, 2-(Trifluoromethyl)-6-chromonyl methyl);

Groups Capable of Photolytic Cleavage (m-Nitrophenyl, 3,5-Dimethoxybenzyl, o-Nitrobenzyl, 3,4-Dimethoxy-6-nitrobenzyl, Phenyl (o-nitrophenyl)methyl); Urea-Type Derivatives (Phenothiazinyl-(10)-carbonyl Derivative, N′-p-Toluenesulfonylaminocarbonyl, N′-Phenylaminothiocarbonyl); Other Carbamates (t-Amyl, S-Benzyl Thiocarbamate, p-Cyanobenzyl, Cyclobutyl, Cyclohexyl, Cyclopentyl, Cyclopropylmethyl, p-Decyloxybenzyl, Diisopropylmethyl, 2,2-Dimethoxycarbonylvinyl, o-(N,N-Dimethyl-carboxamido)benzyl, 1,1-Dimethyl-3-(N,N-dimethylcarboxamido)propyl, 1,1-Dimethylpropynyl, Di(2-pyridyl)methyl, 2-Furanylmethyl, 2-Iodoethyl, Isobutyl, Isonicotinyl. More typically, amino protecting groups include carbamates and amides, still more typically, N-acetyl groups.

Groups capable of biological cleavage typically include prodrugs. Some exemplary groups are described in “Design of Prodrugs”, Hans Bundgaard (Elsevier, N.Y., 1985, ISBN 0-444-80675-X) (Bundgaard) and will not be detailed here. In particular, Bundgaard, at pages 1-92, describes prodrugs and their biological cleavage reactions for a number of functional group types. Prodrugs for carboxyl and hydroxyl groups are detailed in Bundgaard at pages 3 to 10, for amides, imides and other NH-acidic compounds at pages 10 to 27, amines at pages 27 to 43, and cyclic prodrugs at pages 62 to 70. These moieties are optionally bonded to the steroid at one, two or more of the variable groups that are bonded to the rings in the F1Cs, e.g., one or more R 1 -R 6 , R 10 , R 15 , R 17 and R 18 .

In some embodiments one or more F1Cs or groups of F1Cs may be excluded from one or more of the uses disclosed herein. For example, if the subject has or is susceptible to developing a memory impairing neurological disorder or memory impairment condition, excluded compounds can include 5-androstene-3β-ol-7, 17-dione or 5-androstene-3β,7-diol-17-one or a derivative of these compounds that can has a group at the 7-position that can convert to —OH or ═O by hydrolysis. In other cases, the F1Cs can exclude one or more of 4-pregnene-11β, 17α,21-triol-3,20-dione, 17α,21-dihydroxypregn-4-ene-3,11,20-trione, 11β,21-dihydroxy-3,20-dioxopregn-4-en-18-al, 11β, 17α,21-trihydroxypregna-1,4-diene-3,20-dione, 17α,21-dihydroxypregna-1,4-diene-3,11,20-trione, 3β-hydroxypregn-5-ene-20-one, 3β-hydroxyandrost-5-ene-17-one, pregn-4-ene-3,20-dione, 21-hydroxypregn-4-ene-3,20-dione, 9-fluoro-11β, 16α,21-trihydroxy-16-methylpregna-1,4-diene-3,20-dione, 9-fluoro-11β, 16α, 17,21-tetrahydroxypregna-1,4-diene-3,20-dione, 9-fluoro-11β, 17α,21-trihydroxy-16-methylpregna-1,4-diene-3,20-dione, dehydroepiandrosterone-3-sulfate, 1,4-pregnadiene-17α,21-diol-3,11,20-trione, androsterone, androsterone acetate, androsterone propionate, androsterone benzoate, androst-5-ene-3β, 17β-diol, androst-5-ene-3β, 17β-diol-3-acetate, androst-5-ene-3β, 17β-diol-17-acetate, androst-5-ene-3β, 17β-diol-3β, 17-diacetate, androst-5-ene-3β, 17β-diol-17-benzoate, androst-5-ene-3β, 17β-diol-3-acetate-17-benzoate, androst-4-ene-3β, 17-dione, androst-5-ene-3β,7β, 17β-triol, androst-5-ene-3β,7α, 17β-triol, dehydroepiandrosterone, 4-dihydrotestosterone, 5α-dihydrotestosterone, dromostanolone, dromostanolone propionate, ethylestrenol, nandrolone phenpropionate, nandrolone decanoate, nandrolone furylpropionate, nandrolone cyclohexanepropionate, nandrolone benzoate, nandrolone cyclohexanecarboxylate, oxandrolone, stanozolol, testosterone, methyl testosterone, testolactone, oxymetholone, fluoxymesterone, acetoxypregnenolone, allylestrenol, anagestone acetate, chlormadinone acetate, cyproterone, cyproterone acetate, desogestrel, dihydrogesterone, dimethisterone, ethisterone (17α-ethynyltestosterone), ethynodiol diacetate, fluorogestone acetate, gestadene, hydroxyprogesterone, hydroxyprogesterone acetate, hydroxyprogesterone caproate, 3-ketodesogestrel, hydroxymethylprogesterone, hydroxymethylprogesterone acetate, levonorgestrel, lynestrenol, medrogestone, medroxyprogesterone acetate, megestrol, megestrol acetate, melengestrol acetate, norethindrone, norethindrone acetate, norethisterone, norethisterone acetate, norethynodrel, norgestimate, norgestrel, norgestrienone, normethisterone, and progesterone, progesterone, cyproterone acetate, norethindrone, norethindrone acetate, levonorgestrel, an ester of any of the foregoing compounds (e.g., acetate, enanthate, propionate, isopropionate, cyclopropionate, isobutyrate, butyrate, valerate, caproate, isocaproate, hexanoate, heptanoate, octanoate, nonanoate, decanoate, undecanoate, phenylacetate or benzoate esters, e.g., hydroxyl esters), a naturally occurring glucorcorticoid, a species disclosed herein or a derivative of any of these that can convert to these molecules by hydrolysis or metabolism, e.g., a metabolizable or hydrolyzable ester or ether such as a cyclic ketal, an acetate, a diacetete, a proprionate, a diproprionate, or an O-alkyl, an acyl, e.g., —C(O)—C1-C6 alkyl or another moiety that is bonded at, e.g., a variable group such as for R 1 -R 6 .

Dosages of F1C and dosing protocols or methods. In treating any of the conditions or symptoms disclosed herein, one can continuously or intermittently administer the F1C(s) to a subject having or susceptible to developing the condition or symptom. In treating a condition such as an infection, a hyperproliferation condition, an inflammation condition or another condition disclosed herein with a F1C using an intermittent dosing can avoid or ameliorate some of the undesired aspects normally associated with discontinuous dosing. Such undesired aspects include development of resistance of a pathogen such as a pathogen disclosed herein, e.g., a virus or bacterium such as HIV or Staphylococcus aureus or a parasite such as a Plasmodium parasite , to the therapeutic agent, failure of the patient or subject to adhere to a daily dosing regimen or reduction of the dosages of other therapeutic agents and/or their associated unwanted side effects or toxicities, e.g., reduction or a toxic effect of a chemotherapy or radiation exposure. In any of the continuous or intermittent dosing protocols described herein, other appropriate treatments can be applied as the subject's clinical situation dictates. Suitable other appropriate treatments or therapeutic agents are described elsewhere herein and in the cited references.

In any of the continuous or in any step(s) in the intermittent dosing protocols described herein, or in treating any of the diseases, conditions or symptoms described herein, the F1C(s) can be administered by one or more suitable routes, e.g., oral, buccal, sublingual, intramuscular (i.m.), subcutaneous (s.c.), intravenous (i.v.), intradermal, another parenteral route or by an aerosol. The effective daily dose in such methods will typically comprise about 0.05 mg/kg/day to about 200 mg/kg/day, about 0.1 to about 100 mg/kg/day, about 6-45 mg/kg/day, about 1-6 mg/kg/day, including about 0.2 mg/kg/day, 0.5 mg/kg/day, about 1 mg/kg/day, about 2 mg/kg/day, about 4 mg/kg/day, about 6 mg/kg/day, about 10 mg/kg/day, about 20 mg/kg/day, about 40 mg/kg/day or about 100 mg/kg/day. Higher dosages, e.g., about 250 mg/kg/day, about 300 mg/kg/day or about 350 mg/kg/day can also be utilized, e.g., in veterinary applications. One can administer the F1C(s) orally using about 4 to about 60 mg/kg/day, usually about 6-30 mg/kg/day. In some embodiments, the intermittent dosing methods exclude dosing protocols that are commonly used to deliver contraceptive steroids to, e.g., human females, such as daily dosing for 21 days, followed by no dosing for 7 days. For humans, dosing is generally about 0.005 mg/kg/day to about 30 mg/kg/day, typically about 0.5-5 mg/kg/day. Low dosages for humans such as about 0.005 mg/kg/day to about 0.2 mg/kg/day or about 0.25-10 mg/day, can be used with, e.g., local, topical, transmucosal or intravenous administration and higher dosages such as about 0.1 mg/kg/day to about 20 mg/kg/day or about 5-200 mg/day, can be used, e.g., for oral, subcutaneous or other systemic or local administration route. For non-human subjects, e.g., mammals such as rodents or primates, the effective daily dosage may comprise about 0.05 mg/kg/day to about 350 mg/kg/day. F1C formulation dosages or daily doses or unit doses or subdoses for subjects such as humans and mammals include, e.g., about 1, 5, 10, 15, 20, 25, 50, 75, 100, 125, 15β, 175, 200, 225, 250, 275, 300, 325, 350, 400 or 450 mg of the F1C.

An effective dosage or an effective amount of a F1C(s) is one that is sufficient to result in, e.g., a detectable change in a symptom or an immune parameter such as one described herein. An effective dosage (or daily dosage) may be administered to a subject over a period of time, e.g., at least about 1-14 days before a symptom change or an immune parameter detectably changes. Effective amounts of a F1C can be delivered using the dosages and dosing protocols described herein.

In some embodiments, F1C are used to treat, ameliorate, prevent or slow the progression of a condition or disease described herein by continuous daily dosing of the F1C for 1 day to 1, 2, 3 years or more. In related embodiments, F1C are used to treat, ameliorate, prevent or slow the progression of a condition or disease described herein by continuous dosing the F1C every other day or dosing every third, fourth, fifth, sixth, seventh or 14 th day over a time period of 3 days to 1, 2, 3 years or more, e.g., dosing for about 2, 3, 4, 5, 6 or 7 days or about 1, 2, 3, 4, 6, 8, 10, 12, 16, 20, 24 or more weeks. Daily doses in any of these dosing regimens or protocols may be subdivided into 2 or 3 subdoses.

Intermittent dosing protocols include administration of a F1C, e.g., orally, topically or parenterally as follows: (1) daily dosing or dosing every other day or dosing every third day or dosing every fourth day or dosing every fifth day or dosing every seventh day for about 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21 or 28 days to about 190 days or more, e.g., 1 or 2 years, (2) no dosing of the F1C for 1 to about 190 consecutive days (e.g., about 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12 days to about 20 days), (3) daily dosing for about 3 to about 190 days (e.g., about 3 to about 20 days), and (4) optionally repeating step (2) or a variation of step (2) and (5) optionally repeating the steps (1), (2), (3) and (4) 1, 2, 3, 4, 5, 6, 10, 15, 20, 30 or more times. In some embodiments, the dosing of steps (1) and (3) are the same, while in others, step (1) dosing is for a longer time than step (3). Less frequently, step (1) dosing will be for a shorter time. In some embodiments, steps (1)-(4) or (1)-(5) of the dosing protocol described above where step (4) is included, is repeated at least one time, e.g., at least 2, 3, 4, 5 or 6 times. For conditions that tend to remain chronic, e.g., HIV infection or other chronic conditions described herein, any of these intermittent dosing protocols can be maintained over a relatively long time period, e.g., for at least about 4 months or 6 months to about 5 or more years.

In some embodiments, the number of days of dosing in steps (1) and (3) is the same in each round of treatment, i.e., each time period in step (1) and (3) is the same in the initial and subsequent rounds of the method. In other embodiments they differ. Thus, in some embodiments, step (1) may comprise dosing of about 1 mg/day to about 1500 mg/day of a F1C for 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 or more consecutive days. Then, step (2) may comprise not administering any F1C for at least about 2, 3, 4, 5, 6, 7, 14, 21, 28, 42, 56, 84, 98, 112 or more consecutive days. Step (3) could comprise dosing of a F1C for 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more consecutive days. When step (4) is included it is typically about 1 day to about 3 months, usually 3 days to about 6 weeks. On days when the F1C is administered to the subject, it may be delivered in a single dose or in two, three or more subdoses at, e.g., about 12 hour or about 8 hour time intervals.

Exemplary embodiments comprise (1) administering a F1C(s) once every (as a single dose or as 2 or 3 daily subdoses) 2 days, every 3 days or every 4 days or once per week for about 3, 5, 7, 9, 11, 13, 14, 15, 21, 28 or more days, followed by (2) no dosing for about 2, 3, 4, 5, 6, 10, 14, 15, 21, 20, 25, 28, 30, 35, 40, 42, 45, 49, 56, 60, 70, 77, 84, 98, 112 or more days and then (3) administering the F1C(s) at least once more on one day, e.g., administering the F1C(s) as described in step (1), (4) not dosing for 2, 3, 4, 5, 7 or more days, e.g., as described in step (2) for 1, 2, 3, 4, 5, 6, 7 or 8 weeks, and (5) optionally repeating steps (1), (2), (3) and (4) 1, 2, 3, 4, 5 or 6 times or more. Any of the dosing protocols described herein may be coincident or essentially coincident with the appearance or expected appearance of a clinical condition, e.g., dosing with a F1C may commence at about 1, 2 or 3 hours after to about 1, 2, 3, 4 or 5 days after exposure of a subject to radiation or a chemotherapy such as a cancer chemotherapy, to prevent or treat, e.g., reduce the length and/or severity of an acute or chronic side-effect such as neutropenia, such as grade 3 or grade 4 neutropenia, thrombocytopenia, lung fibrosis or inflammation that can be associated with the radiation exposure or the chemotherapy.

Other embodiments comprise (1) administering a F1C(s) once every day (as a single dose or as 2 or 3 daily subdoses) for 3-15 or about 8-12 days, followed by (2) no dosing for 1, 2, 3, 4, 5, 6, 10, 15, 20, 25, 30, 35, 40, 45, 50, 56, 70, 84, 98, 112 or more days and then (3) administering the F1C(s) at least once more on one day, e.g., administering the F1C(s) once per day for about 3-15 or about 8-12 consecutive days essentially as described in step (1) and (4) optionally repeating steps (1), (2) and (3) 1, 2, 3, 4, 5 or 6 times or more. In a subset of these embodiments (1) comprises administering a F1C(s) once every day for about 5, 6, 7, 8, 9 or 10 days, followed by (2) no dosing for about 10-40 days, (3) administering the F1C(s) at least once more on one day, e.g., administering the F1C(s) once per day for about 10 days (4) repeating step (2) or a variation, e.g., no dosing for about 5-45 days, and (5) optionally repeating steps (1), (2), (3) and (4) or a variation thereof those steps 1, 2, 3, 4, 5 or 6 times or more, (5) administering by s.c. or i.m. injection of about 5-45 mg/kg/dose, about 6-43 mg/kg/dose or about 7-43 mg/kg/dose of a group 3 compound such as compound 1.1.5.9 in group 3 described below, once each 1, 2, 3, 4, 5, 6, 7, 8 or 10 days over a period of about 15-28 days, optionally beginning at about 1-72 hours after, about 1-48 hours after, about 1-24 hours after or about 24-72 hours after exposure of the subject to radiation or a cytotoxic chemotherapy, (6) administering orally or by s.c. or i.m. injection about 0.5-10 mg/kg/dose, e.g., about 1.5-3 mg/kg/dose of a group 3 compound such as compound 1.1.5.1 described below, once each 1, 2, 3, 4, 5, 6, 7 or 8 days over a period of about 15-30 days, e.g., over a period of 12, 14, 15, 16, 17, 19, 20, 21, 22, 23, 24, 25, 26 or 32 days, optionally beginning at about 1-72 hours after, about 1-48 hours after, about 1-24 hours after or about 24-72 hours after exposure of the subject to radiation or a cytotoxic chemotherapy.

Any of the dosing protocols described herein may be repeated to coincide or essentially coincide as described above or elsewhere herein with cycles of a chemotherapy or radiation exposure, or with the appearance of symptoms of a clinical condition or disease, e.g., fever, fatigue or pain. Thus periods of 1 week or 2 weeks or 4 weeks to several months, e.g., 2, 3, 4, 5, 6, 7, 8 or more months to about 24 months or about 36 months or more may separate cycles of continuous or intermittent dosing with a F1C. Any given dosing protocol may be selected to provide selected levels of the F1C in serum, blood or tissue for selected time periods. Thus, a dosing protocol may be selected to attain a blood, serum or tissue level of a F1C that is about 0.5 nM to about 4000 nM, e.g., about 1-1000 nm, about 10-800 nm or about 30-650 nM (about 1-800 ng/mL or 10-250 ng/mL in blood or serum), for at least about 1-24 hours per day, e.g., for about 1-2 hours, about 2-8 hours or about 2-12 hours per day, during an entire dosing period or most of a dosing period, e.g., beginning at about 1, 2, 3 or 4 days into a continuous (daily) or intermittent dosing protocol, and/or on days when dosing occurs and/or for several days after to about 1, 2, 3, 4, 5, 6, 7 or 8 weeks after a dosing protocol has ended.

One aspect of the continuous and intermittent dosing protocols is monitoring the subject's response to a particular dosing regimen or schedule, e.g., to any intermittent administration method disclosed herein. For example, while dosing a subject who has a viral infection (e.g., HCV, HIV, SIV, SHIV), one can measure the subject's or pathogen's response, e.g., amelioration of one or more symptoms or a change in infectious particles or viral DNA or RNA in the serum or a change in an immune parameter of interest. Once a response is observed dosing can be continued for one, two or three additional days, followed by discontinuing the dosing for at least one day (at least 24 hours), usually for at least about 2, 3, 4, 5, 6, 7, 14, 21, 28, 42, 56, 70, 84, 98, 112 or more days. Once the subject's response shows signs of remission (e.g., a symptom begins to intensify, viral serum DNA or RNA begins to increase or an immune parameter, e.g., as described herein, begins to deteriorate), dosing can be resumed for another course. An aspect of the subject's response to F1C(s) is that the subject may show a measurable response within a short time, usually about 5-10 days, which allows straightforward tracking of the subject's response, e.g., by monitoring viral titer in peripheral white blood cells (“PBMC”), by measuring viral nucleic acid levels in the blood or by measuring a white blood cell population(s) or expression of a cytokine or interleukin by e.g., white blood cells or a subset(s) thereof. One may monitor one or more immune cell subsets, e.g., NK, LAK, dendritic cells or cells that mediate ADCC immune responses, during and after intermittent dosing to monitor the subject's response and to determine when further administration of the F1C is indicated. These cell subsets are monitored as described herein, e.g., by flow cytometry.

For any of the treatments or methods described herein, prolonged beneficial effects or a sustained immune response by a subject may result from a single administration or short course, e.g, about 1-5 days or about 8 days to about 4 months, of continuous or intermittent administration of a F1C. A single administration means that a F1C is administered to the subject in one, two, three or more doses within a 24 hour period and no further administration of any F1C to the subject occurs for at least about 4-90 days, e.g., about for at least about 30 days to about 2 months, or for about 1.5, 2, 3, 4, 5, 6 or more months. Prolonged beneficial effects or immune responses may also persist after a short course of treatment has been completed (e.g., daily dosing for 2, 3, 4, 5 or 6 days) and the subject is no longer receiving any F1C, or, in some cases, any other therapeutic treatment to treat the primary cause of the subject's pathological condition. Such beneficial effects can persist for more than about 5-30 days, e.g., for at least about 21, 28, 42, 56, 70, 84, 98, 112 or more days. Thus, administration of a F1C provides a method to help protect a subject against progression of an infection or against adverse consequences of unwanted immune reactions, e.g., inflammation or immunosuppression or as disclosed herein, without any dosing of the compound for at least 1, 2 or 3 months after an initial dosing protocol.

Other intermittent dosing embodiments comprise administering to a subject having or susceptible to a condition as described herein an effective amount of a F1C using an initial induction or high dosing regimen. The high dosing regimen may comprise, e.g., 1, 2, 3, 4, 5, 6, 7 or more daily doses of about 4 to about 40 mg/kg that are administered daily, every other day, every 3 rd day, every 4 th day or every 5 th day. Then, the subject is not dosed with a F1C for a period, e.g., of about 5, 7, 14, 21, 28, 42, 56, 70, 84, 98, 112 or more consecutive days. Then a lower daily dosing regimen is administered to the subject, e.g., about 0.2 mg/kg to about 4 or about 6 mg/kg, essentially as described for the high dosing regimen. Alternatively, this low dosing regimen may comprise 1, 2, 3, 6 or more rounds of a low to moderate initial level, e.g., about 2 to about 10 mg/kg/day, optionally followed by subsequent rounds of daily dosing that decrease the initial low to moderate level by about 10%, 20%, 30%, 40% or more in each subsequent round of treatment, which is continued until administration is discontinued. These embodiments can be used with any of the dosing protocols described herein.

Dosages of the F1C, continuous or intermittent dose protocols, routes of administration and the use of combination therapies with other standard therapeutic agents or treatments could be applied essentially as described above for any of the diseases or conditions that are disclosed herein. Thus, the F1Cs may be administered prophylactically or therapeutically in chronic or acute conditions. In acute conditions, the F1Cs may also be administered at the time of occurrence or relatively soon after an acute event such as the onset of surgery, a migraine or the occurrence of trauma, e.g., a central nervous system injury, a cerebral stroke or myocardial infarction. For acute events, a F1C may thus be administered concurrently, e.g., within about 15 minutes or about 30 minutes or about 45 minutes of the onset or occurrence of the acute event, or at a later time, e.g., at about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 18, 20, 22, 24, 26, 28, 30, 36, 42, 48, 54, 60, 72, 84, 96, 108 or 120 hours after the onset or occurrence of the acute event or at any range of times defined by any two of these later times. The F1Cs may thus be administered at about 4-120 hours, about 6-120 hours, about 8-48 hours, 8-24 hours, 8-12 hours, 10-12 hours, 10-14 hours, 10-16 hours, about 10-24 hours, 12-14 hours or about 12-16 hours after an acute event starts, occurs or is believed to have begun, e.g., after a surgical procedure has been completed or after a radiation treatment has ended or after a cytotoxic chemotherapy or a myelosuppressive cancer chemotherapy has been administered to the subject.

Alternatively, the F1Cs may be administered before, e.g., within about 15 minutes, about 30 minutes or about 45 minutes before the onset or occurrence of a planned or anticipated acute event, or at an earlier time, e.g., at about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 18, 20, 22, 24, 26, 28, 30, 36, 42, 48, 54, 60, 72, 84, 96, 108 or 120 hours before the onset or occurrence of the acute event. The F1Cs may thus be administered at about 6-120 hours, about 8-48 hours, about 10-24 hours, about 10-16, or about 12-16 hours before the planned or anticipated acute event, e.g., before a planned surgery or a radiation treatment starts or occurs.

Formulations and compositions for preparing formulations. Invention embodiments include formulations described here and elsewhere in this disclosure. While it is possible for the F1C(s) to be administered to a subject or incubated with a subject's cells in vitro as the compound alone, it is usual to use F1C in a formulation or at least in a composition that contains 1, 2, 3, 4, 5, 6 or more excipients. The formulations, which are useful for veterinary or human pharmaceutical use, comprise at least one F1C, together with 1, 2, 3, 4, 5, 6 or more excipients and optionally one or more additional therapeutic ingredients.

The invention includes compositions comprising one or more pharmaceutically acceptable excipients or carriers. The compositions are used to prepare formulations suitable for human or animal use. Formulations may be designed or intended for oral, rectal, nasal, topical or transmucosal (including buccal, sublingual, ocular, vaginal and rectal) and parenteral (including subcutaneous, intramuscular, intravenous, intradermal, intrathecal, intraocular and epidural) administration. In general, aqueous and non-aqueous liquid or cream formulations are delivered by a parenteral, oral or topical route. In other embodiments, the F1C(s) may be present as an aqueous or a non-aqueous liquid formulation or a solid formulation suitable for administration by any route, e.g., oral, topical, buccal, sublingual, parenteral, aerosol, a depot such as a subcutaneous depot or an intraperitoneal or intramuscular depot or a rectal or vaginal suppository. The preferred route may vary with, for example, the subject's pathological condition or weight or the subject's response to therapy with a F1C or other therapy that is used or that is appropriate to the circumstances. The F1C formulations can also be administered by two or more routes, e.g., subcutaneous injection and buccal or sublingual, where these delivery methods are essentially simultaneous or they may be essentially sequential with little or no temporal overlap in the times at which the compound is administered to the subject.

The formulations include those suitable for the foregoing administration routes. The formulations may conveniently be presented in unit dosage form and may be prepared by any of the methods known in the art of pharmacy. Techniques, excipients and dosage forms are found in, e.g., Remington's Pharmaceutical Sciences , Mack Publishing Co., Easton, Pa. 1985, 17 th edition; Nema et al., PDA J. Pharm. Sci. Tech. 1997 51:166-171 ; Pharmaceutical Coating Technology, 1995, G. Cole, et al., editors, Taylor & Francis, ISBN 0 136628915 ; Pharmaceutical Dosage Forms, 1992 2 nd revised edition, volumes 1 and 2, H. A. Lieberman, et al., editors, Marcel Dekker, ISBN 0824793870 ; Pharmaceutical Preformulation, 1998, pages 1-306, J. T. Carstensen, Technomic Publishing Co. ISBN 1566766907; and Encyclopedia of Pharmaceutical Technology , volumes 1, 2 and 3, 2 nd edition, 2002, J. Swarbrick and J. C Boylan, editors, Marcel Dekker, Inc., New York, N.Y.

Methods to make invention formulations include the step of bringing into association or contacting a F1C(s) with one or more excipient, such as one described herein or in the cited references. In general the formulations are prepared by uniformly and intimately bringing into association the F1C(s) with liquid excipients or finely divided solid excipients or both, and then, if appropriate, shaping the product.

Formulations suitable for oral administration are prepared as discrete units such as capsules, soft gelatin capsules (softgels), cachets, tablets or caplets each containing a predetermined amount of the F1C(s). F1C formulations can also be present as a powder or granules or as a solution or a suspension, colloid or gel in an aqueous liquid or base or in a non-aqueous liquid or base; or as an oil-in-water liquid emulsion or a water-in-oil liquid emulsion. The F1C formulations may also be a bolus, electuary or paste. Suspension formulations will typically contain about 0.5% w/w or about 1% w/w to about 5%, 10%, 15% or 20% w/w of the F1C, which can be for parenteral use or for other routes of administration, e.g., oral softgels.

A tablet is made by compression or molding, optionally with one or more accessory ingredients. Compressed tablets may be prepared by compressing in a suitable machine the F1C(s) in a free-flowing form such as a powder or granules, optionally mixed with a binder, lubricant, inert diluent, preservative, surface active or dispersing agent. Molded tablets may be made by molding in a suitable machine a mixture of the powdered or granulated F1C and one or more excipients, which are optionally moistened, with an inert liquid diluent or excipient. The tablets may optionally be coated or scored and optionally are formulated so as to provide slow or controlled release of the F1C(s) therefrom. An exemplary tablet or caplet formulation suitable for buccal or sublingual delivery of a F1C to a subject's tissues comprises about 25 or 50 mg of a F1C comprising per 25 mg of the F1C about 6.2 mg povidone, about 0.62 mg magnesium stearate, about 45 mg mannitol and about 48 mg of compressible sucrose.

For infections of the eye or other external tissues e.g., the mouth or skin, the formulations are typically applied as a topical ointment or cream containing the F1C(s) in an amount of, for example, about 0.075 to about 20% w/w (including F1C(s) in a range between about 0.1% and 20% in increments of 0.1% w/w such as about 0.6% w/w, about 0.7% w/w, about 1% w/w, about 1.5% w/w, about 2% w/w, about 2.5 w/w, about 3% w/w, about 5% w/w, about 7% w/w, about 10% w/w etc.), including about 0.2 to 15% w/w and about 0.5 to 10% w/w. When formulated in an ointment, the F1C(s) may be employed with either a paraffinic or a water-miscible ointment base. Alternatively, they may be formulated in a cream with an oil-in-water cream base.

If desired, the aqueous phase of the cream base may include, for example, at least 30% w/w of a polyhydric alcohol, i.e. an alcohol having two or more hydroxyl groups such as propylene glycol, butane 1,3-diol, butane 1,4-diol, mannitol, sorbitol, glycerol and a polyethylene glycol (including, e.g., PEG 300 and PEG 400) and mixtures thereof. The topical formulations may include a compound that enhances absorption or penetration of the F1C(s) through the skin or other affected areas. Examples of such dermal penetration enhancers include dimethyl sulphoxide and related analogs.

The oily phase of the emulsion formulations may be constituted from known excipients in a known manner. While the phase may comprise an emulsifier or emulgent, it typically comprises a mixture of at least one emulsifier with a fat or an oil or with both a fat and an oil. A hydrophilic emulsifier may be included together with a lipophilic emulsifier, which acts as a stabilizer. Some embodiments include both an oil and a fat. Together, the emulsifier(s) with or without stabilizer(s) make up the so-called emulsifying wax, and the wax together with the oil and fat make up the so-called emulsifying ointment base which forms the oily dispersed phase of the cream formulations.

Emulgents and emulsion stabilizers suitable for use in the formulations include Tween60™, Span80™, cetostearyl alcohol, benzyl alcohol, myristyl alcohol, glyceryl mono-stearate and sodium lauryl sulfate. Other excipients include emulsifying wax, propyl gallate, citric acid, lactic acid, polysorbate 80, sodium chloride, isopropyl palmitate, glycerin and white petrolatum.

The choice of suitable oils or fats for the formulation is based on achieving the desired cosmetic properties. Creams are generally a non-greasy, non-staining and washable products with suitable consistency to avoid leakage from tubes or other containers. Straight or branched chain, mono- or dibasic alkyl esters such as di-isoadipate, isocetyl stearate, propylene glycol diester of coconut fatty acids, isopropyl myristate, decyl oleate, isopropyl palmitate, butyl stearate, 2-ethylhexyl palmitate or a blend of branched chain esters known as Crodamol CAP may be used. These may be used alone or in combination depending on the properties required. Alternatively, high melting point lipids such as white soft paraffin and/or liquid paraffin or other mineral oils are used.

Formulations suitable for topical administration to the eye include eye drops, which are usually sterile, wherein the F1C(s) is dissolved or suspended in a suitable excipient(s), including an aqueous solvent for a F1C(s) that comprise at least about 0.5, one, two or more charges at pH values near neutrality, e.g., about pH 6-8. The F1C(s) is typically present in such formulations in a concentration of about 0.5-20% w/w, about 1-10% w/w or about 2-5% w/w.

Formulations suitable for topical administration to oral mucosa include lozenges or tablets comprising the F1C(s) in a flavored basis or a monosaccharide or disaccharide such as sucrose, lactose or glucose and acacia or tragacanth; pastilles comprising the F1C(s) in an inert basis such as gelatin and glycerin, or sucrose and acacia; and mouthwashes comprising the F1C(s) in a suitable liquid excipient(s). In some embodiments, the lozenges or tablets optionally comprise the property of rapid dissolution or disintegration, e.g., disintegration within about 15 seconds to about 2 minutes, while in others, the lozenges or tablets comprise the property of slower dissolution or disintegration, e.g., disintegration within about 2 minutes to about 10 minutes or more.

Formulations for rectal administration may be presented as a suppository with a suitable base comprising for example cocoa butter or a salicylate.

Formulations suitable for vaginal administration may be presented as pessaries, tampons, creams, gels, pastes, foams or spray formulations containing in addition to the F1C(s) such excipients as are known in the art to be appropriate.

Formulations suitable for parenteral administration include aqueous and non-aqueous sterile injection solutions which may contain anti-oxidants, buffers, bacteriostats, salts (e.g., NaCl, potassium or sodium carbonate or bicarbonate or potassium or sodium phosphates) and solutes which render the formulation isotonic with the blood of the intended subject; and aqueous and non-aqueous sterile suspensions which may include suspending agents or thickening agents. In general, the F1C that is present in liquid compositions or formulations is completely dissolved in aqueous or non-aqueous excipients. However, in some embodiments, e.g., transient compositions or some formulations, the F1C is partially dissolved while the remaining portion is present as a solid, which can be a suspension or a colloid.

Formulations suitable for parenteral delivery of F1Cs to subjects such as humans or animals typically comprise 1, 2, 3, 4, 5, 6 or more excipients. Exemplary embodiments include (1) any two, three or four of propylene glycol, PEG200, PEG300, ethanol, benzyl alcohol and benzyl benzoate and (2) any two, three or four of propylene glycol, PEG100, PEG200, PEG300, PEG400, benzyl alcohol and benzyl benzoate. Typically such formulations will contain both propylene glycol and one or more PEGs, e.g., PEG100, PEG200, PEG300 or PEG400, which enhance the solubility of the F1C by a cosolvent effect.

Formulations, or compositions disclosed herein for use to make formulations suitable for administration by the routes disclosed herein optionally comprise an average particle size in the range of about 0.01 to about 500 microns, about 0.1 to about 100 microns or about 0.5 to about 75 microns. Average particle sizes include a range between 0.01 and 500 microns in 0.05 micron or in 0.1 micron or other increments, e.g., an average particle size of about 0.05, 0.1, 0.2, 0.3, 0.4, 0.5, 0.7, 1, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 5.5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 50, 60, 75, 85, 100, 120, 150, etc. microns). The F1C itself that is used to make a formulation can have one, two or more of these average particle sizes. When F1Cs or compositions that comprise a F1C are used as intermediates to make a formulation, they may comprise one, two, three or more of these average particle sizes, or size ranges. In preparing any of the compositions or formulations that are disclosed herein and that comprise a F1C (and optionally one or more excipients), one may optionally mill, sieve or otherwise granulate the compound or composition to obtain a desired particle size, e.g., as described above.

Milling or micronization by any other method may occur before or after the F1C is contacted with one or more excipients. For example, one may mill a F1C to obtain an average particle size (or diameter) of about 0.05-50 μM or about 0.5-10 μM (e.g., about 0.02, 0.04, 0.05, 0.07, 0.1, 0.5, 1, 1.5, 2, 2.5, 5, 10, 15, 20, 30, 40, 50, 60, 80, 100 or 120 μM average particle size or diameter) before contacting the milled F1C with a liquid or solid excipient. In some cases the F1C is milled or sieved to obtain an average particle size of about 5 μm or about 10 μm before it is contacted with a solid or liquid excipient(s) to obtain a solution or suspension or a powder suitable for making a tablet, capsule or other dosage form as described herein or in the cited references. Micronized compound may be prepared using any suitable process for obtaining small particles, e.g., controlled precipitation from a solution, micronizing or milling, a number of which are known in the art. The micronized particles may include a percentage of particles that are less than or equal to about 0.1-20 μm in diameter. Ranges of average particle sizes include F1Cs of about 0.04-0.6 μm, about 0.04-1.0 μm, about 0.05-0.6 μm, about 0.05-1.0 μm, about 0.1-0.4 μm, about 0.5-1 μm, about 1-20 μm or about 2-50 μm.

As used herein, reference to an average particle size or an average particle diameter means that the material, e.g., a F1C(s), an excipient(s) or a composition that comprises both, is ground, milled, sieved or otherwise treated so as to comprise the specified average size. It is to be understood that some particles may be larger or smaller, but the composition or the F1C(s) will comprise a significant proportion of the material with the specified size or within an acceptable range of the specified size, e.g., at least about 70% or about 80% of the particles within about 30% to about 50% of the average size or diameter. Micronization methods include milling by ball mills, pin mills, jet mills (e.g., fluid energy jet mills) and grinding, sieving and precipitation of a compound(s) from a solution, see, e.g., U.S. Pat. Nos. 4,919,341, 5,202,129, 5,271,944, 5,424,077 and 5455049. Average particle size is determined by known methods, e.g., transmission electron microscopy, scanning electron microscopy, light microscopy, X-ray diffractometry, light scattering methods or Coulter counter analysis.

Thus, the F1Cs may comprise a powder that consists of one, two or more of these average particle sizes and the powder may be contacted with a solid excipient(s), suitably mixed and optionally compressed or formed into a desired shape. Alternatively, such a F1C(s) is contacted with a liquid excipient(s) to prepare a liquid formulation or a liquid composition that is incorporated into a solid formulation. Suitable micronized formulations thus include aqueous or oily solutions or suspensions of the F1C(s).

Formulations suitable for aerosol administration typically will comprise a fine powder, e.g., having an average particle size of about 0.1 to about 20 microns or any one, two or more of the average particle sizes within this range that are described above. The powder is typically delivered by rapid inhalation through the nasal passage or by inhalation through the mouth so as to reach the bronchioles or alveolar sacs of the lungs.

Formulations suitable for aerosol, dry powder or tablet administration may be prepared according to conventional methods and may be delivered with other therapeutic agents such as compounds heretofore used in the treatment or prophylaxis of viral or other infections as described herein. Such formulations may be administered, e.g., orally, parenterally (e.g., intravenous, intramuscular, subcutaneous, intradermal, intrathecal), topically, sublingually or by a buccal or sublingual route.

Micronized F1C is useful, e.g., to facilitate mixing, dissolution or uniform suspension of the F1C in one or more liquid or solid excipients, e.g., a PEG such as PEG 300 or PEG 400, propylene glycol, benzyl benzoate, a complexing agent, such as a cyclodextrin (e.g., an α-, β- or γ-cyclodextrin such as hydroxypropyl-β-cyclodextrin). Micronized F1C is also useful to facilitate uniformly distributing drug substance when the micronized compound is contacted with one or more solid excipients (e.g., a filler, a binder, a disintegrant, complexing agent (e.g., a cyclodextrin such as hydroxypropyl-β-cyclodextrin), a preservative, a buffer or a lubricant).

In related embodiments, suitable compositions or formulations comprise a F1C that is present in two or more physical forms. For example, a liquid composition or formulation may comprise a F1C that is present in solution and as undissolved particles, which may be milled as described herein. Alternatively, a solid composition or formulation may comprise a F1C that is present as an amorphous form and as a crystal or in an encapsulated granule. Such encapsulated granules may comprise a slow release type formulation and the F1C that is present may be in one or more physical forms, e.g., liquids or solids as described herein, but usually as a solid in tablets or other solid formulations.

The formulations are presented in unit-dose or multi-dose containers, for example sealed ampules and vials, and may be stored in a freeze-dried (lyophilized) condition requiring only the addition of the sterile liquid excipient, for example water for injection, immediately prior to use. In general, solid, liquid or other formulations or compositions that comprise a F1C, e.g., unit dosages for solid or liquid formulations, are stored in a sealed container, which may optionally be opaque or nearly opaque (e.g., amber or blue glass or brown plastic) to reduce the amount of light that reaches the formulation or composition. Such containers are also optionally sealed, e.g., hermetically sealed, to prevent or limit exchange of air, water or other gases between the container's contents and air. Extemporaneous injection solutions and suspensions are prepared from sterile powders, granules and tablets as described above. Unit dosage formulations are those containing a daily dose or unit daily sub-dose, as recited herein, or an appropriate fraction thereof, of the F1C(s).

It should be understood that in addition to the ingredients particularly mentioned above the formulations of this invention may include other agents or excipients conventional in the art having regard to the type of formulation in question, for example those suitable for oral administration may include flavoring agents. Excipients include liquids, such as benzyl benzoate, cottonseed oil, N,N-dimethylacetamide, a C 2-12 alcohol (e.g., ethanol), glycerol, peanut oil, vitamin E, poppyseed oil, safflower oil, sesame oil, soybean oil and vegetable oil. Excipients may optionally exclude one or more excipient, e.g., chloroform, dioxane, vegetable oil, DMSO, other excipients or any combination of these. Other excipients are components typically used in the pharmaceutical formulation arts, e.g., one, two or more of fillers, binders, disintegrants, dispersants, preservatives, glidants and lubricants, e.g., povidone, crospovidone, corn starch, carboxymethyl cellulose, hydroxypropyl methylcellulose, microcrystalline cellulose, gum arabic, polysorbate 80, butylparaben, propylparaben, methylparaben, BHA, EDTA, sodium lauryl sulfate, sodium chloride, potassium chloride, titanium dioxide, magnesium stearate, castor oil, olive oil, vegetable oil, buffering agents such as sodium hydroxide, monobasic sodium phosphate, dibasic sodium phosphate, potassium hydroxide, monobasic potassium phosphate, dibasic potassium phosphate, tribasic potassium phosphate, potassium carbonate, potassium bicarbonate, ammonium hydroxide, ammonium chloride, saccharides such as mannitol, glucose, fructose, sucrose or lactose any of which may be compressible or any of which may be spray dried, milled, micronized or otherwise treated to obtained desired characteristics.

Formulations made from or comprising a F1C are optionally stored under conditions that limit the amount of light or water that reaches the formulation, e.g., in a sealed container that holds a formulation or unit dosage form and optionally contains silica gel or activated carbon. Water permeation characteristics of containers have been described, e.g., Containers—Permeation, Chapter, USP 23, 1995, U.S. Pharmacopeial Convention, Inc., Rockville, Md., p. 1787. Storage of BrEA hemihydrate or formulations that contain it is typically at about 4-30° C.

The invention further provides veterinary compositions comprising at least one F1C together with a veterinary excipient(s) therefor. Veterinary excipients are materials useful for the purpose of administering the composition and may be solid, liquid or gaseous materials that are otherwise inert or acceptable in the veterinary art and are compatible with the F1C(s). These veterinary compositions may be administered orally, parenterally or by any other desired route.

Invention formulations include controlled release or slow release formulations containing a F1C(s) in which the release of the F1C(s) is controlled or regulated to allow less frequency dosing or to improve the pharmacokinetic or toxicity profile of a given F1C(s). Polymers and other materials that are suitable to prepare controlled release formulations that comprise a F1C have been described, e.g., U.S. Pat. Nos. 4,652,443, 4,800,085, 4,808,416, 5,013,727, 5,188,840.

Formulations may thus contain microcapsules, granules or other shaped forms and may comprise a F1C and a slow release polymer or polymer matrix that comprises or consists of one or more of ethylene dimethacrylate, diethylene glycol dimethacrylate, diethylene glycol diacrylate, triethylene glycol dimethacrylate, triethylene glycol diacrylate, tetrathylene glycol dimethacrylate, tetraethylene glycol diacrylate, polyethylene glycol dimethacrylate, polyethylene glycol diacrylate, diethylaminoethyl dimethacrylate, glycidyl methacrylate, epoxy acrylate, glycidyl acrylate, hydroxyethyl methacrylate, hydroxyethyl acrylate, hydroxypropyl methacrylate, hydroxypropyl acrylate, hydroxybutyl methacrylate, hydroxybutyl acrylate, hydroxyhexyl methacrylate, hydroxyhexyl acrylate, butanediol dimethacrylate, butanediol diacrylate, propanediol dimethacrylate, propanediol diacrylate, pentanediol dimethacrylate, pentanediol diacrylate, hexanediol dimethacrylate, hexanediol diacrylate, neopentyl glycol dimethacrylate, neopentyl glycol diacrylate, trimethylopropane triacrylate, trimethylolpropane trimethacrylate, trimethyloethane triacrylate, trimethylolethane trimethacrylate, polypropyleneglycol diacrylate, and polypropylene glycol dimethacrylate.

Formulations may comprise a liposome or lipid complex that comprises or contains a F1C(s). Such formulations are prepared according to known methods, e.g., U.S. Pat. Nos. 4,427,649, 5,043,165, 5,714,163, 5,744,158, 5,783,211, 5,795,589, 5,795,987, 5,798,348, 5,811,118, 5,820,848, 5,834,016 and 5882678. The liposomes optionally contain an additional therapeutic agent(s), e.g., amphotericin B, cis-platin, adriamycin, a protease inhibitor, a nucleoside or a nucleotide analog, such as one of those mentioned herein. Formulations that comprise liposomes can be delivered to a subject by any standard route, e.g., oral, aerosol or parenteral (e.g., s.c., i.v. or i.m.).

Liposome formulations can be used to enhance delivery of the F1C(s) to certain cell types such as tumor cells (see e.g., U.S. Pat. No. 5,714,163) or to cells of the reticuloendothelial system (“RES”). The RES includes macrophages, mononuclear phagocytic cells, Kupfer cells, cells lining the sinusoids of the spleen, lymph nodes, and bone marrow, and the fibroblastic reticular cells of hematopoietic tissues. In general, RES cells are phagocytic and they are targets for targeted delivery of a F1C(s) in vitro or in vivo using liposomes, or other compositions or formulations. Thus, one can deliver F1C to a neoplasm that is derived from reticuloendothelial tissue (reticuloendothelioma). The liposomes may optionally comprise a peptide from an infectious agent such as a malaria parasite, a virus or a tumor associated antigen. The peptides may facilitate the generation of a MHC class II and B cell response. In other cases a liposomal F1C formulation is useful to obtain suspension F1C formulations.

Invention embodiments include the product made by a process of combining, mixing or otherwise contacting a F1C and one, two or more excipients. Such products are produced by routine methods of contacting the ingredients. Such products optionally contain a diluent, a disintegrant, a lubricant, a binder, or other excipients described herein or in references cited herein.

Other embodiments include compositions that transiently occur when a method step or operation is performed. For example, when a F1C, containing less than about 3% w/w water is contacted with an excipient, e.g., a PEG, an alcohol, propylene glycol benzyl alcohol or benzyl benzoate, the composition before addition of one ingredient with another is a non-homogenous mixture. As the ingredients are contacted, the mixture's homogeneity increases and the proportion of ingredients relative to each other approaches a desired value. Thus, invention compositions, which contain less than about 3% w/w or less than about 2% w/w or less than about 1% w/w or less than about 0.5% w/w water can comprise about 0.0001-99% w/w of a F1C and 1, 2, 3 or more excipients. These transient compositions are intermediates that necessarily arise when one makes an invention composition or formulation and they are included in invention embodiments.

When a F1C and an excipient(s) is contacted or mixed, the final composition may comprise a homogenous mixture or it may comprise a mixture that is not homogenous for one or more of the compounds that are present in the composition. Compositions and formulations that are either homogenous or non-homogenous are included in the scope of the invention. Non-homogenous compositions can be used, e.g., to make controlled release formulations.

Invention embodiments include compositions and formulations that comprise less than about 3% water, a F1C and a compound that is not generally considered suitable for human use but is useful to make an invention formulation for veterinary use. Veterinary formulations are compositions useful for the purpose of administering invention compositions to primates, cats, dogs, horses, cows, rabbits and other subjects and may contain excipients acceptable in the veterinary art and are compatible with F1Cs. These veterinary compositions may not always be suitable for human use because they contain an excipient that is not suitable for human use, e.g., an alcohol other than ethanol such as methanol, propanol or butanol. Typically such excipients will be present at relatively low levels, e.g., about 1-30%, usually about 1-5%.

Invention embodiments include non-aqueous compositions and formulations, e.g., unit dosage forms and sterile solutions or suspensions, that comprise about 1-25% w/w of a F1C, about 20-60% w/w propylene glycol, about 15-55% w/w of more or more PEGs, e.g., PEG100 or PEG200, about 0-5% w/w benzyl benzoate, about 0-5% w/w benzyl alcohol and optionally one or more additional excipients. These non-aqueous formulations will usually contain less than about 3%, 2%, 1%, 0.8%, 0.5%, 0.4%, 0.3%, 0.2% or 0.1% w/w of water. In formulations that contain non-aqueous excipients, the F1C will usually be relatively hydrophobic and will usually not contain any easily charged or ionizable moieties such as free carboxyl groups.

F1Cs may be administered to subjects by transmucosal dosing, e.g., by buccal or sublingual administration. The buccal area generally refers to the subject's mouth and pharynx, and the buccal mucosa includes the mucosa of the mouth and pharynx. The sublingual area refers generally to the mucosa below and adjacent to the tongue. Formulations suitable for buccal or sublingual administration typically comprise about 1-100 mg of F1C per unit dose, often about 2-60 mg. Transmucosal dosages may comprise a slow release or a rapid release formulation or tablet that contains about 1, 5, 10, 15, 20, 25, 30, 35, 40, 50 or 60 mg of a F1C. Slow release formulations will generally degrade or release the F1C from the dosage over a period of about 2 minutes to about 60 minutes or more. Rapid release formulations will generally release the F1C over a period of about 4 seconds to about 2 minutes, typically over about 0.1 to about 1 minute. Solid and liquid buccal or sublingual formulations optionally include one, two, three or more excipients such as fillers, binders, lubricants, antioxidants, preservatives, flavoring agents or disintegrants, e.g., lactose, sucrose, mannitol, Tween-80, magnesium stearate, butylated hydroxyanisole, butylated hydroxytoluene, cyclodextrins (e.g., α-cyclodextrins, β-cyclodextrins, γ-cyclodextrins, hydroxypropyl-β-cyclodextrin, β-cyclodextrin ether comprising one or more hydroxybutyl sulfonate moieties, cyclodextrins as described in U.S. Pat. Nos. 6,610,671 or 6,566,347), carbomers, hydrolyzed polyvinylalcohol, polyethylene oxide, polyacrylates, hydroxypropylmethylcellulose, hydroxypropylcellulose, and combinations thereof. Such formulations may be a unit solid such as a tablet or powder or a liquid. Buccal tablets may comprise a concave surface for contacting the buccal mucosa and adhering to it. A buccal or sublingual dosage may comprise a compressed tablet of a substantially uniform mixture of a bioerodible polymeric carrier, which on sustained contact with the oral mucosa, substantially or completely erodes within a predetermined period in the range of about 10 minutes to about 24 hours. In some embodiments, the F1C is administered by a method for administering the compound to the subject, e.g., to a mammal or a human, comprising affixing a unit dosage or tablet to the subject's buccal mucosa in a region at or near the upper gum between the first bicuspid on the left and the first bicuspid on the right (or an alternative location for the dosage unit is the inner lip area opposing the this upper gum area) and optionally allowing the tablet to remain in place until erosion thereof is complete or nearly complete. Exemplary excipients may comprise a combination of polyethylene oxide and a carbomer, e.g., wherein the polyethylene oxide and the carbomer are in an approximately 1:5 to 5:1 ratio by weight.

Tablets or unit dosages for buccal or sublingual delivery may be about 5 mm in diameter and 2 mm in height, so that the unit dosage occupies about 40 mm 3 . Such dosages will typically weigh less than about 100 mg (e.g., about 5 to 60 mg), with a contact surface area of about 10-30 mm 2 , e.g., about 15-20 mm 2 . Such dosages will generally be about 4-10 mm in diameter and about 1-3 mm in height. When a polymer excipient is used, it optionally comprises a polymer having sufficient tack to ensure that the dosage unit adheres to the buccal mucosa for a sufficient time period, e.g., the time period during which drug is to be delivered to the buccal mucosa. The polymeric excipient is gradually “bioerodible,” and it hydrolyzes, dissolves, erodes or disintegrates (collectively “erodes”) at a predetermined rate upon contact with water or saliva. The polymeric carrier is generally sticky when moist, but not when dry, for convenience in handling. The average molecular weight of the polymer may be about 400 to 1,000,000, or about 1,000 to 100,000. Higher the molecular weight polymers generally erode more slowly.

For these buccal and sublingual dosages, a pharmaceutically acceptable polymer(s) can be used. Such polymers will provide a suitable degree of adhesion and the desired drug release profile, and are generally compatible with the drug to be administered and any other components that may be present in the buccal dosage unit. The polymeric carriers optionally comprise hydrophilic (water-soluble and water-swellable) polymers that adhere to the wet surface of the buccal mucosa. Examples of polymeric carriers that are useful herein include acrylic acid polymers, e.g., those known as “carbomers” (Carbopol™, which may be obtained from B.F. Goodrich, is one such polymer). Other suitable polymers include hydrolyzed polyvinylalcohol; polyethylene oxides (e.g., Sentry polyox™ water soluble resins, available from Union Carbide); polyacrylates (e.g., Gantrez™, which may be obtained from GAF); vinyl polymers and copolymers; polyvinylpyrrolidone; dextran; guar gum; pectins; starches; and cellulosic polymers such as hydroxypropyl methylcellulose, (e.g., Methocel™, which may be obtained from the Dow Chemical Company), hydroxypropyl cellulose (e.g., Klucel™, which may be obtained from Dow), hydroxypropyl cellulose ethers (see, e.g., U.S. Pat. No. 4,704,285 to Alderman), hydroxyethyl cellulose, carboxymethyl cellulose, sodium carboxymethyl cellulose, methylcellulose, ethyl cellulose, cellulose acetate phthalate, cellulose acetate butyrate, and the like. The carrier may also comprise two or more suitable polymers in combination, for example, a carbomer combined in an approximately 1:5 to 5:1 ratio, by weight, with a polyethylene oxide.

Buccal dosages may contain only the F1C and the polymer(s). However, it may be desirable in some cases to include one or more additional excipients. For example, a lubricant may be included to facilitate the process of manufacturing the dosage units; lubricants may also optimize erosion rate and drug flux. If a lubricant is present, it may optionally represent about 0.01 wt. % to about 2 wt. %, or about 0.01 wt. % to 0.5 wt. %, of the dosage unit. Suitable lubricants include, but are not limited to, magnesium stearate, calcium stearate, stearic acid, sodium stearylfumarate, talc, hydrogenated vegetable oils and polyethylene glycol. However, modulating the particle size of the components in the dosage unit and/or the density of the unit can provide a similar effect, e.g., improved manufacturability, and optimization of erosion rate and drug flux without addition of a lubricant.

Other excipients are also optionally incorporated into buccal unit dosages. Such additional optional excipients include, one or more disintegrants, diluents, binders, enhancers, or the like. Examples of disintegrants that may be used include, but are not limited to, cross-linked polyvinylpyrrolidones, such as crospovidone (e.g., Polyplasdone™ XL, which may be obtained from GAF), cross-linked carboxylic methylcelluloses, such as croscarmelose (e.g., Ac-di-sol™, which may be obtained from FMC), alginic acid, and sodium carboxymethyl starches (e.g., Explotab™, which may be obtained from Edward Medell Co., Inc.), methylcellulose, agar bentonite and alginic acid. Suitable diluents are those which are generally useful in pharmaceutical formulations prepared using compression techniques, e.g., dicalcium phosphate dihydrate (e.g., Di-Tab™, which may be obtained from Stauffer), sugars that have been processed by cocrystallization with dextrin (e.g., co-crystallized sucrose and dextrin such as Di-Pak™, which may be obtained from Amstar), lactone, calcium phosphate, cellulose, kaolin, mannitol, sodium chloride, dry starch, powdered sugar and the like. Binders, if used, are those that enhance adhesion. Examples of such binders include, but are not limited to, starch, gelatin and sugars such as sucrose, dextrose, molasses, and lactose. Permeation enhancers may also be present in the novel dosage units in order to increase the rate at which the active agent passes through the buccal mucosa. Examples of permeation enhancers include, but are not limited to, polyethylene glycol monolaurate (“PEGML”), glycerol monolaurate, lecithin, the 1-substituted azacycloheptan-2-ones, particularly 1-n-dodecylcyclaza-cycloheptan-2-one (available under the trademark Azone™ from Nelson Research & Development Co., Irvine, Calif.), lower alkanols (e.g., ethanol), SEPA™ (available from Macrochem Co., Lexington, Mass.), cholic acid, taurocholic acid, bile salt type enhancers, and surfactants such as Tergitol™, Nonoxynol-9™ and TWEEN-80™.

Flavorings are optionally included in buccal or sublingual formulations. Any suitable flavoring may be used, e.g., one or more of mannitol, sucrose, glucose, lactose, lemon, lemon lime, orange, menthol or artificial sweeteners such as aspartame, saccharin sodium, dipotassium glycyrrhizinate, stevia and thaumatin. Some sweeteners such as sucrose may also aid in dissolution or erosion of solid formulations. Coloring agents may also be added, e.g., any of the water soluble FD&C dyes or mixtures thereof, e.g., one or more of FD&C Yellow No. 5, FD&C RED No. 2, FD&C Blue No. 2, etc., food lakes or red iron oxide. In addition such formulations dosages may be formulated with one or more preservatives or bacteriostatic agents, e.g., methyl hydroxybenzoate, propyl hydroxybenzoate, chlorocresol, benzalkonium chloride, or the like.

Other embodiments include solid buccal or sublingual formulations comprising (i) a F1C and (ii) erythritol, (iii) crystalline cellulose and (iv) a disintegrant, e.g., crospovidone. These formulations are capable of buccal disintegration or dissolution and may further comprise mannitol. These formulations may dissolve completely in solely saliva within about 1-10 minutes of administration to a subject. The erythritol is optionally contained in a proportion of about 5-90 parts by weight, based on 100 parts by weight of the solid buccal formulation. The crystalline cellulose is optionally contained in a proportion of about 3-50 parts by weight, based on 100 parts by weight of the formulation. The disintegrant is optionally contained in a proportion of 1-10 parts by weight. In any of the solid buccal or sublingual formulations the ingredients are generally uniformly mixed, although non-uniform mixtures may be used. An exemplary formulation comprises a solid capable of buccal disintegration or dissolution, which comprises (i) about 0.3-50 parts by weight of a F1C, (ii) about 50-80 parts by weight of erythritol, (iii) about 5-20 parts by weight of crystalline cellulose and (iv) about 3-7 parts by weight of a disintegrant, which optionally is one or more of crospovidone, croscarmellose, croscarmellose sodium, carmellose calcium, carboxymethylstarch sodium, low substituted hydroxypropyl cellulose or corn starch. Examples of the crystalline cellulose include products of various grade such as CEOLUS KG801, avicel PH101, avicel PH102, avicel PH301, avicel PH302, avicel RC-591 (crystalline cellulose carmellose sodium) and so on. One crystalline cellulose may be used or two or more species may be used in combination. The disintegrant, e.g., crospovidone, may be used singly or in combination with other disintegrants. Crospovidone includes any cross-linked 1-ethenyl-2-pyrrolidinone homopolymer, and may comprise a polymer of molecular weight of 1,000,000 or more. Examples of commercially available crospovidone include Cross-linked povidone, Kollidon CL, Polyplasdone XL, Polyplasdone XL-10, INF-10 (manufactured by ISP, Inc.), polyvinylpolypyrrolidone, PVPP and 1-vinyl-2-pyrrolidinone homopolymer. The disintegrants are optionally incorporated in a proportion of about 1-15 parts by weight, or about 1-10 parts by weight, or about 3-7 parts by weight, based on 100 parts by weight of the solid formulation.

Some embodiments include a solid buccal or sublingual formulation containing a F1C where unit doses of the formulation substantially or completely disintegrates or erodes within about 20-120 seconds in water at 37° C. or on insertion of the unit dose into the buccal area or upon placement under the tongue. Such formulations may comprise a swellable hydrophilic excipient, a water-soluble or a water-dispersible excipient, e.g., one or more of partially hydrolyzed gelatin, hydrolyzed dextran, dextrin, mannitol, alginates, polyvinyl alcohol, polyvinyl pyrrolidine, water soluble cellulose derivatives, methylcellulose, ethyl cellulose, carboxymethyl cellulose, hydroxymethylcellulose, hydroxypropyl methylcellulose, microcrystalline cellulose, alginates, gelatin, guar gum, gum tragacanth, gum acacia, polyacrylic acid, polymethacrylic acid, polysilicic acid, polylactic acid, polymaleic acid, polyvinyl alcohol, polyethylene glycol, polyvinyl pyrrolidone, nonionic blocked polymers, carbomers, polycarbophils, a water soluble starch, dicalcium phosphate, calcium carbonate, silica or polyethyleneglycol, e.g., PEG1000, PEG2000 or a polyethylene oxide (“PEO”), PEO1000, PEO100000 or PEO5000000.

Other embodiments include the product obtained by storing invention compositions or formulations, e.g., unit dosage forms or compositions used to make formulations, at about 4-40° C. for at least about 30 days, e.g., storage at ambient temperature for about 1-24 months. Invention formulations will typically be stored in hermetically or induction sealed containers for these time periods. Compositions and formulations that comprise a F1C will typically be held in closed or sealed containers, particularly when the composition is a formulation for pharmaceutical or veterinary use.

Typical containers for storage of compositions and formulations that comprise a F1C will limit the amount of water that reaches the materials contained therein. Typically, formulations are packaged in hermetically or induction sealed containers. The containers are usually induction sealed. Water permeation characteristics of containers have been described, e.g., Containers—Permeation, chapter, USP 23 <671>, United States Pharmacopeial Convention, Inc., 12601 Twinbrook Parkway, Rockville, Md. 20852, pp.: 1787 et seq. (1995).

Immune modulation. The F1Cs, or the biologically active substances produced from these compounds by hydrolysis or metabolism in vivo, have a number of clinical and non-clinical applications. The compounds are generally useful to correct immune dysregulation, e.g., imbalanced immune responses to disease conditions, pathogens or the like, suppression of an innate or acquired immune response(s) and inflammation conditions in vertebrate or mammalian subjects, e.g., as disclosed herein. Thus, while the compounds will generally enhance a deficient immune response in a given clinical condition, they will generally reduce the same immune response when it is too active in a different clinical condition. For example, they can enhance insufficient or suboptimal Th1 immune responses, reduce excess or undesirable Th2 immune responses, reduce excess or undesirable Th1 immune responses or enhance insufficient or suboptimal Th2 immune responses or they can reduce excess or undesirable inflammation or one or more of its symptoms. The compounds will generally also modulate dysregulated Tc1 and Tc2 immune responses (associated with CD8 + T cells) in a similar manner, e.g., excessive Tc1 or Tc2 responses will be detectably decreased and deficient or suboptimal Tc1 or Tc2 responses will generally be detectably enhanced.

Invention embodiments include a method to modulate a subject's innate immunity, Th1 immune responses, Tc1 immune responses, Th2 immune responses or Tc2 immune responses comprising administering an effective amount of a F1C to a subject or delivering the F1C to the subject's tissues. Other methods include modulating an immune or cellular response in a subject in need thereof comprising administering to the subject, or delivering to the subject's tissues, an effective amount of a compound of formula 1. Immune and cellular response modulation includes enhancing Th1 immune responses, reducing Th2 immune responses, reducing Th1 immune responses, enhancing Th2 immune responses, reducing unwanted or pathological inflammation, enhancing hematopoiesis or modulating the synthesis, level or a biological activity of a biomolecule such as (1) a transcription factor such as a nuclear hormone receptor or an associated receptor factor, (2) a purine such as adenosine, (3) a nucleotide cofactor such as NADPH, (4) a cytokine or interleukin or a receptor for a cytokine or interleukin, or (5) another biomolecule as disclosed herein. Such enhancements, reductions, levels or activities are usually in an easily detectable range, e.g., a change compared to a suitable control of at least about 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95% or a range that is between about any two of these values. Typically the subject is in need of such treatment, e.g., by having a clinical condition disclosed herein or being subject to developing such a condition, e.g., having been exposed or potentially exposed to a pathogen or having a predisposing condition such as precancer.

In modulating one or more activities of Th1, Th2, Tc1 or Tc2 cells or their function(s), the F1Cs will typically detectably modulate one, two, three or more factors, e.g., immune cell subsets or populations, cytokines, interleukins, surface antigens such as a CD molecule(s) and/or their receptors that affect the development, migration, numbers or biological function(s) of such cells. When a Th1 or Tc1 cell or population is affected, the F1Cs will typically increase or decrease the synthesis or level of one, two or more of an associated effector factor, e.g., IFNγ, IL-2, IL-12, IL-18, T-bet, PPARα and PPARγ or a cell surface molecule, e.g., as disclosed herein or in the cited references, that is associated with or needed for normal, optimal or enhanced Th1 or Tc1 cells or cell function. Such