Zn2+-chelating motif-tethered short-chain fatty acids as a novel class of histone deacetylase inhibitors

A histone deacetylase inhibitor having the formula:

A histone deacetylase inhibitor having the formula:

A histone deacetylase inhibitor chosen from N-(2-Amino-phenyl)-4-[(2-propyl-pentanoylamino)-methyl]-benzamide; N-Hydroxy-4-[(2-propyl-pentanoylamino)-methyl]-benzamide; N-(2-Amino-phenyl)-4-(2-propyl-pentanoylamino)-benzamide; N-Hydroxy-4-(2-propyl-pentanoylamino)-benzamide; 2-Propyl-pentanoic acid {4-[(2-amino-phenylcarbamoyl)-methyl]-phenyl]-amide; 2-Propyl-pentanoic acid (4-hydroxycarbamoyl-methyl-phenyl)-amide; 2-Propyl-pentanoic acid {4-[(2-amino-phenylcarbamoyl)-ethyl]-phenyl}-amide; 2-Propyl-pentanoic acid [4-(2-hydroxycarbamoyl-ethyl)-phenyl]-amide; 2-Propyl-pentanoic acid {4-[2-(2-amino-phenylcarbamoyl)-vinyl]-phenyl}-amide; and 2-Propyl-pentanoic acid [4-(2-hydroxycarbamoyl-vinyl)-phenyl]-amide.

A histone deacetylase inhibitor chosen from N-(2-Amino-phenyl)-4-(butyrylamino-methyl)-benzamide; N-(2-Amino-phenyl)-4-(phenylacetylamino-methyl)-benzamide; N-(2-Amino-phenyl)-4-[(4-phenyl-butyrylamino)-methyl]-benzamide; 4-(Butyrylamino-methyl)-N-hydroxy-benzamide; N-hydroxy-4-(phenylacetylamino-methyl)-benzamide; N-hydroxy-4-[(4-phenyl-butyrylamino)-methyl]-benzamide; 4-Butyrylamino-N-hydroxy-benzamide; N-hydroxy-4-phenylacetylamino-benzamide; N-hydroxy-4-(4-phenylbutyrylamino)-benzamide; and N-[4-(2-Hydroxycarbamoyl-ethyl)-phenyl]-butyramide.

A histone deacetylase inhibitor chosen from N-hydroxy-3-(4-phenylacetylamino-phenyl)-propionamide; N-[4-(2-Hydroxycarbamoyl-ethyl)-phenyl]-4-phenyl-butyramide; N-(2-Amino-phenyl)-4-[(2-phenyl-butyrylamino)-methyl]-benzamide; N-(2-Amino-phenyl)-4-[(3-phenyl-butyrylamino)-methyl]-benzamide; N-hydroxy-4-(2-phenylbutyrylamino)-benzamide; N-hydroxy-4-(3-phenylbutyrylamino)-benzamide; N-[4-(2-Hydroxycarbamoyl-ethyl)-phenyl]-2-phenyl-butyramide; N-[4-(2-Hydroxycarbamoyl-ethyl)-phenyl]-3-phenyl-butyramide; N-hydroxy-4-[(2-phenyl-butyrylamino)-methyl]-benzamide; and N-hydroxy-4-[(3-phenyl-butyrylamino)-methyl]-benzamide.

A histone deacetylase inhibitor chosen from 4-Benzoylamino-N-hydroxy-benzamide; 4-(4-methyl)-Benzoylamino-N-hydroxy-benzamide; 4-(4-chloro)-Benzoylamino-N-hydroxy-benzamide; 4-(4-bromo)-Benzoylamino-N-hydroxy-benzamide; 4-(4-tert-butyl)-Benzoylamino-N-hydroxy-benzamide; 4-(4-phenyl)-Benzoylamino-N-hydroxy-benzamide; 4-(4-methoxyl)-Benzoylamino-N-hydroxy-benzamide; 4-(4-trifluoromethyl)-Benzoylamino-N-hydroxy-benzamide; 4-(4-nitro)-Benzoylamino-N-hydroxy-benzamide; and Pyridine-2-carboxylic acid (4-hydroxycarbamoyl-phenyl)-amide.

A histone deacetylase inhibitor chosen from N-hydroxy-4-(2-methyl-2-phenyl-propionylamino)-benzamide; N-hydroxy-4-(3-methyl-2-phenyl-butyrylamino)-benzamide; N-hydroxy-4-(3-phenyl-propionylamino)-benzamide; Dimethyl-4-phenyl-butyrylamino)-N-hydroxy-benzamide; N-hydroxy-4-[methyl-(4-phenyl-butyryl)-amino]-benzamide; N-hydroxy-4-(2-phenyl-propionylamino)-benzamide; N-hydroxy-4-(2-methoxy-2-phenyl-acetylamino)-benzamide; 4-Diphenylacetylamino-N-hydroxy-benzamide; N-hydroxy-4-[2-(4-isobutyl-phenyl)-propionylamino]-benzamide; and N-(2-Amino-phenyl)-4-phenylacetylamino-benzamide.

A histone deacetylase inhibitor chosen from N-(2-Amino-phenyl)-4-(5-phenyl-pentanoylamino)-benzamide; N-(2-Amino-phenyl)-4-(2-phenyl-butyrylamino)-benzamide; N-(2-Amino-phenyl)-4-(2,2-dimethyl-4-phenyl-butyrylamino)-benzamide; N-(2-Amino-phenyl)-4-(3-phenyl-propionylamino)-benzamide; N-(2-Amino-phenyl)-4-(4-phenyl-butyrylamino)-benzamide; N-(2-Amino-phenyl)-4-(3-phenyl-butyrylamino)-benzamide; N-(2-Amino-phenyl)-4-(3-methyl-2-phenyl-butyrylamino)-benzamide; N-(2-Amino-phenyl)-4-(2-methyl-2-phenyl-propionylamino)-benzamide; N-(2-Amino-phenyl)-4-[2-(4-isobutyl-phenyl)-propionylamino]-benzamide; and N-hydroxy-4-[2-(S)-phenylbutyrylamino]-benzamide.

A histone deacetylase inhibitor chosen from N-hydroxy-4-[2-(R)-phenylbutyrylamino]-benzamide; N-[4-(2-Hydroxycarbamoyl-ethyl)-phenyl]-2-(S)-phenyl-butyramide; N-[4-(2-Hydroxycarbamoyl-ethyl)-phenyl]-2-(R)-phenyl-butyramide; N-hydroxy-4-(3-(S)-phenylbutyrylamino)-benzamide; N-hydroxy-4-(3-(R)-phenylbutyrylamino)-benzamide; N-hydroxy-4-[3-(S)-phenylbutyrylamino]-benzamide; and N-hydroxy-4-[3-(R)-phenylbutyrylamino]-benzamide.

A histone deacetylase inhibitor having the structure:

A histone deacetylase inhibitor having the structure:

A histone deacetylase inhibitor having the structure: