Methods and compositions for stimulating neurite growth

A method for stimulating neurite growth in nerve cells comprising the step of contacting said nerve cells with a composition comprising a neur6trophic amount of a compound with affinity for FKBP12 having the formula (II): ##STR11## and pharmaceutically acceptable derivatives thereof, wherein A' is CH.sub.2, oxygen, NH or N-(C1-C4 alkyl); B' and W are independently: (i) hydrogen, Ar' (C1-C10)-straight or branched alkyl, (C2-C10)-straight or branched alkenyl or alkynyl, (C5-C7)-cycloalkyl substituted (C1-C6)-straigb. t or branched alkyl, (C2-C6)-straight or branched a_tkenyl or alkynyl, (C5-C7)-cycloalkenyl substituted (C1-C6)-straight or branched alkyl, (C2-C6)-straight or branched alkenyl or alkynyl, or Ar' substituted (C1-C6)-straight or branched alkyl, (C2-C6)-straight or branched alkenyl or alkynyl wherein, in each case, any one of the CH.sub.2 groups of said alkyl, alkenyl or alkynyl chains may be optionally replaced by a heteroatom selected from the group consisting of O, S, SO, SO.sub.2, N, and NR, wherein R is selected from the group consisting of hydrogen, (C1-C4)-straight or branched alkyl, (C2-C4)-straight or branched alkenyl or alkynyl, and (C1-C4) bridging alkyl wherein a bridge is formed between the nitrogen and a carbon atom of said heteroatom-containing chain to form a ring, and wherein said ring is optionally fused to an Ar' group; or ##STR12## wherein Q' is hydrogen, (C1-C6)-straight or branched alkyl or (C2-C6)-straight or branched alkenyl or alkynyl; and T' is Ar' or substituted 5-7 membered cycloalkyl with substituents at positions 3 and 4 which are independently selected from the group consisting of oxo, hydrogen, hydroxyl, )--(C1-C4)-alkyl, and O--(C2-C4)-alkenyl; wherein Ar' is a carbocyclic aromatic group selected from the group consisting of phenyl, 1 -naphthyl, 2 -naphthyl, indenyl, azulenyl, fluorenyl, and anthracenyl; or a heterocyclic aromatic group selected from the group consisting of 2-furyl, 3-furyl, 2-thienyl, 3-thienyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, pyrazolyl, isoxazolyl, isothiazolyl, 1,2,3-oxadiazolyl, 1,2,3-triazolyl, 1,3,4-thiadiazolyl, pyridazinyl, pyrimidinyl, pyrazinyl, 1,3,5-triazinyl, 1,3,5-trithianyl, indolizinyl, indolyl, isoindolyl, 3H-indolyl, indolinyl, benzo[b]furanyl, benzo[b]thiophenyl, 1H-indazolyl, benzimidazolyl, benzthiazolyl, purinyl, 4H-quinolizinyl, quinolinyl, isoquinolinyl, cinnolinyl, phthalazinyl, quinazolinyl, quinoxalinyl, 1,8-naphthyridinyl, pteridinyl, carbazolyl, acridinyl, phenazinyl, phenothiazinyl, and phenoxazinyl; and wherein Ar' may contain one to three substituents which are independently selected from the group consisting of hydrogen, halogen, hydroxyl, hydroxymethyl, nitro, trifluoromethyl, trifluoromethoxy, (C1-C6)-straight or branched alkyl, (C2-C6)-straight or branched alkenyl, O--[(C1-C4)-straight or branched alkyl], O--[(C2-C4)-straight or branched alkenyl], O-benzyl, O-phenyl, 1,2-methylenedioxy, amino, carboxyl, N-[(C1-C5)-straight or branched alkyl or (C2-C5)-straight or branched alkenyl)carboxamides, N,N-di-[(C1-C5)-straight or branched alkyl or (C2-C5)-straight or branched alkenyl)]carboxamides, N-morpholinocarboxamide, N-benzylcarboxamide, N-thiomorpholinocarboxamide, N-picolinoylcarboxamide, O--X, CH.sub.2 --(CH.sub.2).sub.q --X, O--(CH.sub.2).sub.q --X, (CH.sub.2).sub.q --O--X, and CH.dbd.CH--X; wherein X is 4-methoxyphenyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, pyrazyl, quinolyl, 3,5-dimethylisoxazoyl, isoxazoyl, 2-methylthiazoyl, thiazoyl, 2-thienyl, 3-thienyl, or pyrimidyl; and q is 0-2; G is U'; M is either oxygen or CH--U'; provided that if G is hydrogen, then M is CH--U' or if M is oxygen, then G is U'; wherein U' is hydrogen, O--[(C1-C4)-straight or branched alkyl] or O--[(C2-C4)straight or branched alkenyl], (C1-C6)-straight or branched alkyl or (C2-C6)-straight or branched alkenyl, (C5-C7)-cycloalkyl or (C5-C7)-cycloalkenyl substituted with (C1-C4)-straight or branched alkyl or (C2-C4)-straight or branched alkenyl, (C1-C4)-alkyl or (C2-C4)-alkenyl]-Y or Y; wherein Y is selected from the group consisting of phenyl, 1-naphthyl, 2-naphthyl, indenyl, azulenyl, fluorenyl, anthracenyl, 2-pyrrolinyl, 3-pyrrolinyl, pyrolidinyl, 1,3-dioxolyl, 2-imidazolinyl, imidazolidinyl, 2H-pyranyl, 4H-pyranyl, piperidyl, 1,4-dioxanyl, morpholinyl, 1,4-dithianyl, thiomorpholinyl, piperazinyl, quinuclidinyl, and heterocyclic aromatic groups as defined for Ar' above; and wherein Y may contain one to three substituents which are independently selected from the group consisting of hydrogen, halogen, hydroxyl, hydroxymethyl, nitro, trifluoromethyl, trifluoromethoxy, (C1-C6)-straight or branched alkyl, (C2-C6)-straight or branched alkenyl, O--[(C1-C4)-straight or branched alkyl], O--[(C2-C4)-straight or branched alkenyl], O-benzyl, O-phenyl, 1,2-methylenedioxy, amino, and carboxyl; J' is hydrogen, (C1-C2) alkyl or benzyl; K is (E1-C4)-straight or branched alkyl, benzyl or cyclohexylmethyl, or J' and K are taken together to form a 5-7 membered heterocyclic ring which may contain a heteroatom selected from the group consisting of O, S, SO and SO.sub.2 ; and m is 0-3; wherein said compound is not a compound of formula (i).