Inhibitors of Histone Deacetylase

A compound of formula (1):

• or an N-oxide, hydrate, solvate, pharmaceutically acceptable salt, complex or prodrug thereof, or a racemic or scalemic mixture, diastereomer, enantiomer or tautomer thereof, wherein
• T is NH2 or OH;
• A is selected from the group consisting of arylene, heteroarylene, cycloalkylene and heterocyclylene, each of which is optionally substituted;
• and
• X is
• wherein
• Y═N or CH,
• n1=0-4 and
• Z1 is selected from the group consisting of R9—, R13—C(O)—, R13—C(S)—, R7—N(R2)—, R6—O—, R10—S—, R13—S(O)1-2, R5—C(O)—O—, R15—O—C(O)—, R15—C(O)—S—, R15—S—C(O)—, R11—C(O)—N(R2)—, R13—N(R2)—C(O)—, R15—C(S)—O—, R15—O—C(S)—, R15—C(S)—S—, R15—S—C(S)—, R15—C(S)—N(R2)—, R15—N(R2)—C(S)—, R5—O—C(O)—O—, R15—O—C(O)—S—, R15—S—C(O)—O—, R12—O—C(O)—N(R2)—, R8—N(R2)—C(O)—O—, R5—O—C(S)—O—, R15—O—C(S)—S—, R15—S—C(S)—O—, R15—O—C(S)—N(R2)—, R15—N(R2)—C(S)—O—, R15—S—C(O)—S—, R15—S—C(O)—N(R2)—, R15—N(R2)—C(O)—S—, R15—S—C(S)—S—, R5—N(R2)—C(O)—N(R2)—, R5—N(R2)—C(S)—N(R2)—, R15—N(R2)—C(S)—S—, R15—S—C(S)—N(R2)—, R5—NH—C(N(R2))—NH—, R5—S(O)0-2—N(R2)—, R5—N(R2)—S(O)0-2— and R15—N(R2)—S(O)0-2—N(R2)—;
• with the proviso that if n1 is 1 or 2 and Z1 is R9—, R13—C(O)—, R7—N(R2)—, R6—O—, R10—S—, R13—S(O)1-2, R15—C(O)—O—, R15—O—C(O)—, R11—C(O)—N(R2)—, R13—N(R2)—C(O)—, R12—O—C(O)—N(R2)—, R8—N(R2)—C(O)—O—, R5—S(O)2—N(R2)— or R5—N(R2)—S(O)2—, then A is not thienyl, thiadiazolyl, thiazolyl, pyrimidyl, pyrazinyl, pyridazinyl, pyridyl, triazinyl or tetrazinyl;
• in which
• each R2 is independently selected from the group consisting of hydrogen, (C1-C5 alkyl)-, Ar—(C0-C4 alkyl-, Het-(C0-C4 alkyl)-, Hca-(C0-C4 alkyl)-, Cak-(C0-C4 alkyl)-, R14—CO—, R14—SO2-, R14—CO—NH— and R14—CO—O—, in which each alkyl is optionally substituted;
• each R5 is independently selected from the group consisting of H—, optionally substituted (C1-C6 hydrocarbyl)-, Ar—(C1-C6 hydrocarbyl)-, Het-(C1-C6 hydrocarbyl)-, Hca-(C0-C6 hydrocarbyl)- and Cak-(C0-C6 hydrocarbyl)-;
• each R6 is independently selected from the group consisting of H—, substituted (C1-C6 hydrocarbyl)- with the proviso that if the (C1-C6 hydrocarbyl) has only one substituent, it is not halo or amino, Hca-(C0-C1 or C3-C6 hydrocarbyl)- and Cak-(C0-C6 hydrocarbyl)-;
• each R7 is independently selected from the group consisting of H, optionally substituted (C1-C6 hydrocarbyl)-, Hca-(C0-C1 or C3-C6 hydrocarbyl)- and Cak-(C0-C6 hydrocarbyl)-;
• each R8 is independently selected from the group consisting of optionally substituted (C1-C6 hydrocarbyl)-, Ar—(C1-C6 hydrocarbyl)-, Het-(C1-C6 hydrocarbyl)-, Hca-(C0-C6 hydrocarbyl)- and Cak-(C0-C6 hydrocarbyl)-, with the proviso that R8 is not 2(morpholin-4-yl)ethyl;
• each R9 is independently selected from the group consisting of Hca-(C0-C6 hydrocarbyl)- and Cak-(C0-C6 hydrocarbyl)-;
• each R10 is independently selected from the group consisting of H—, Hca-(C0-C6 hydrocarbyl)- and Cak-(C0-C6 hydrocarbyl)-;
• each R11 is independently selected from the group consisting of H—, (C1-C6 hydrocarbyl)-, Hca-(C0-C6 hydrocarbyl)- and Cak-(C0-C6 hydrocarbyl)-;
• each R12 is independently selected from the group consisting of optionally substituted (C1-C6 hydrocarbyl)-, Ar—(C1-C6 hydrocarbyl)-, Het-(C1-C6 hydrocarbyl)-, Hca-(C0-C6 hydrocarbyl)-, Cak-(C0-C6 hydrocarbyl)-;
• each R13 is independently selected from the group consisting of H—, optionally substituted (C1-C6 hydrocarbyl)-, Hca-(C0-C6 hydrocarbyl)- and Cak-(C0-C6 hydrocarbyl)-;
• each R14 is independently selected from the group consisting of Ar— and optionally substituted (C1-C6 hydrocarbyl)-;
• and
• each R15 is independently selected from the group consisting of H—, optionally substituted (C1-C6 hydrocarbyl)-, Ar—(C0-C6 hydrocarbyl)-, Het-(C0-C6 hydrocarbyl)-, Hca-(C0-C6 hydrocarbyl)- and Cak-(C0-C6 hydrocarbyl)-;
• in which any (C1-C6 hydrocarbyl)- moiety is optionally substituted, and each Ar is independently an optionally substituted aryl, each Het is independently an optionally substituted heteroaryl, each Hca is independently an optionally substituted heterocycloalkyl, and each Cak is independently an optionally substituted cycloalkyl.