Inhibitors of histone deacetylase

An inhibitor of histone deacetylase represented by the formula

• Cy—L2—Ar—Y2—C(O)NH—Z
• wherein
• Cy is cycloalkyl, aryl, heteroaryl, or heterocyclyl, any of which may be optionally substituted, provided that Cy is not a (spirocycloalkyl)heterocyclyl;
• L2 is C1-C6 saturated alkylene or C2-C6 alkenylene, wherein the alkylene or alkenylene optionally may be substituted, provided that L2 is not —C(O)—, and wherein one of the carbon atoms of the alkylene optionally may be replaced by a heteroatom moiety selected from the group consisting of O;
• NR′, R′ being alkyl, acyl, or hydrogen;
• S;
• S(O);
• or S(O)2;
• Ar is arylene, wherein said arylene optionally may be additionally substituted and optionally may be fused to an aryl or heteroaryl ring, or to a saturated or partially unsaturated cycloalkyl or heterocyclic ring, any of which may be optionally substituted;
• and
• Y2 is a chemical bond or a straight- or branched-chain saturated alkylene, which may be optionally substituted, provided that the alkylene is not substituted with a substituent of the formula —C(O)R wherein R comprises an α-amino acyl moiety;
• and
• Z is selected from the group consisting of anilinyl, pyridyl, thiadiazolyl, and —O—M, M being H or a pharmaceutically acceptable cation;
• provided that when the carbon atom to which Cy is attached is oxo substituted, then Cy and Z are not both pyridyl.

An inhibitor of histone deacetylase represented by the formula

• Cy—L3—Ar—Y3—C(O)NH—Z
• wherein
• Cy is cycloalkyl, aryl, heteroaryl, or heterocyclyl, any of which may be optionally substituted, provided that Cy is not a (spirocycloalkyl)heterocyclyl;
• L3 is selected from the group consisting of
• (a) —(CH2)m—W—, where m is 0, 1, 2, 3, or 4, and W is selected from the group consisting of —C(O)NH—, —S(O)2NH—, —NHC(O)—, —NHS(O)2—, and —NH—C(O)—NH—;
• and
• (b) C1-C6 alkylene or C2-C6 alkenylene, wherein the alkylene or alkenylene optionally may be substituted, provided that L3 is not —C(O)—, and wherein one of the carbon atoms of the alkylene optionally may be replaced by O;
• NR′, R′ being alkyl, acyl, or hydrogen;
• S;
• S(O);
• or S(O)2;
• Ar is arylene, wherein said arylene optionally may be additionally substituted and optionally may be fused to an aryl or heteroaryl ring, or to a saturated or partially unsaturated cycloalkyl or heterocyclic ring, any of which may be optionally substituted;
• and
• Y3 is C2 alkenylene or C2 alkynylene, wherein one or both carbon atoms of the alkenylene optionally may be substituted with alkyl, aryl, alkaryl, or aralkyl;
• and
• Z is selected from the group consisting of anilinyl, pyridyl, thiadiazolyl, and —O—M, M being H or a pharmaceutically acceptable cation;
• provided that when Cy is unsubstituted phenyl, Ar is not phenyl wherein L3 and Y3 are oriented ortho or meta to each other.