Inhibitors of histone deacetylase

A compound of formula I:

• or a pharmaceutically acceptable salt, hydrate, solvate, or prodrug thereof, wherein:
• U is selected from single bond, CR2eR2f-CR2gR2h, NR2d, NR2d-NR2d′, and O;
• J′ is selected from NH2 and SH;
• each X is independently selected from hydrogen, deuterium, methyl, CF3, and halogen;
• R2d is selected from NH2, hydrogen, and C1-C8 alkyl;
• R2d′ is selected from NH2, hydrogen, and C1-C8 alkyl;
• R2e, R2f, R2g, and R2h are each independently selected from hydrogen, halogen, and C1-C4 alkyl;
• or taken together R2e and R2f, or R2g and R2h taken together form ═O;
• or taken together two of R2e, R2f, R2g, and R2h on two adjacent carbon atoms together with the bond between said adjacent carbon atoms form a carbon-carbon double bond;
• R2aR2bR2cV- is of the formula:
• J is selected from O, C, and S;
• provided that:
• when J is C, Ru is selected from hydrogen, C1-C8 alkyl, (C1-C8 alkyl)CF3, (C1-C8 alkyl)OH, and C(O)R3a, wherein R3a is C1-C8 alkyl;
• and
• when J is O or S, Ru is absent;
• v is selected from 0, 1, 2, 3, 4, 5, 6, 7, and 8;
• d and d′ are each independently selected from 0, 1, 2, and 3;
• R2c is selected from hydrogen, halogen, OH, NH2, and C1-C8 alkyl;
• each Rx is independently selected from hydrogen, (CH2)zNH2, (CH2)zNHR3, (CH2)zNR3R3, OR3, OCF3, OCH2F, OCHF2, (CH2)z-aromatic ring, (CH2)z-heterocyclic ring, hydroxyl, halogen, C1-C8 alkyl, (C1-C8 alkyl)CF3, (C1-C8 alkyl)OH, C(O)R3, (CH2)zC(O)NH2, (CH2)zC(O)NHR3, (CH2)zC(O)NR3R3, (CH2)zNHC(O)R4, and (CH2)zNR4C(O)R4;
• or taken together two Rx attached to the same carbon atom form ═O;
• or taken together two Rx form a C3-C8 cycloalkyl ring, C4-C8 cycloalkenyl ring, or 3 to 8 membered, saturated or partially unsaturated, heterocyclic ring, wherein said cycloalkyl ring, cycloalkenyl ring, and heterocyclic ring are each independently substituted with one or more Rz;
• or taken together two Rx form an aromatic ring or heteroaromatic ring, wherein said aromatic ring and heteroaromatic ring are fused with
• and are each independently substituted with one or more Rz;
• each Rz is independently selected from hydrogen, halogen, C1-C4 alkyl, OH, OR3, CF3, OCF3, OCH2F, OCHF2, NH2, NHR3, NR3R3, and C(O)CH3;
• each R3 is independently selected from C1-C8 alkyl and O(C1-C8 alkyl);
• each R4 is independently selected from C1-C8 alkyl and CF3;
• R5 is selected from O(C2-C8 alkyl), C2-C8 alkyl, C2-C8 alkenyl, (CH2)u-5-6 membered, saturated, unsaturated, or partially unsaturated, heterocyclic ring, (CH2)v″-C4-C8 cycloalkyl ring, (C1-C8-alkyl)w-C4-C8cycloalkenyl ring, (CH2)s-aromatic ring, and (CH2)s-heteroaromatic ring, and wherein said heterocyclic ring, cycloalkyl ring, cycloalkenyl ring, heteroaromatic ring, and aromatic ring are each independently substituted with one or more Ry, and said alkenyl is substituted with one or more RT;
• each Ry is independently selected from hydrogen, halogen, OR6, NH2, NHR6, NR6R6, OH, CF3, phenyl, C(O)R6, C1-C8 alkyl, C2-C8 alkenyl, and C2-C8 alkynyl;
• each R6 is independently C1-C8 alkyl;
• each RT is independently selected from hydrogen, halogen, Si(R3)3, phenyl, and C1-C8 alkyl;
• u is selected from 0, 1, and 2;
• v″ is selected from 0, 1, and 2;
• w is selected from 0, 1, and 2;
• s is selected from 0, 1, and 2;
• t is selected from 0, 1, and 2;
• and
• each z is independently selected from 0, 1, 2, and 3.