Patent ID: 7579372

Claim:
A method of inhibiting histone deacetylation activity in cells comprising contacting the cells with an effective amount of a compound containing an alpha-ketoepoxide group, wherein the compound is not trapoxin, thereby treating one or more disorders mediated by histone deacetylase wherein the compound is of formula (I): wherein A is a cyclic moiety selected from the group consisting of C 3-14 cycloalkyl, 3-14 membered heterocycloalkyl, C 4-14 cycloalkenyl, 3-8 membered heterocycloalkenyl, aryl, and heteroaryl; the cyclic moiety being optionally substituted with alkyl, alkenyl, alkynyl, alkoxy, hydroxyl, hydroxylalkyl, halo, haloalkyl, amino, thio, alkylthio, arylthio, aralkylthio, acylthio, alkylcarbonyloxy, alkyloxycarbonyl, alkylcarbonyl, alkylsulfonylamino, aminosulfonyl, or alkylsulfonyl; or A is a saturated branched C 3-12 hydrocarbon chain or an unsaturated branched C 3-12 hydrocarbon chain optionally interrupted by —O—, —S—, —N(R a )—, —C(O)—, —N(R a )—SO 2 —, —SO 2 —N(R a )—, —N(R a )—C(O)—O—, —O—C(O)—N(R a )—, —N(R a )—C(O)—N(R b )—, —O—C(O)—, —C(O)—O—, —O—SO 2 —, —SO 2 —O—, or —O—C(O)—O—, where each of R a and R b , independently, is hydrogen, alkyl, alkenyl, alkynyl, alkoxy, hydroxylalkyl, hydroxyl, or haloalkyl; each of the saturated and the unsaturated branched hydrocarbon chain being optionally substituted with alkyl, alkenyl, alkynyl, alkoxy, hydroxyl, hydroxylalkyl, halo, haloalkyl, amino, thio, alkylthio, arylthio, aralkylthio, acylthio, alkylcarbonyloxy, alkyloxycarbonyl, alkylcarbonyl, alkylsulfonylamino, aminosulfonyl, or alkylsulfonyl; each of Y 1 and Y 2 , independently, is —CH 2 —, —O—, —S—, —N(R c )—, —N(R c )—C(O)—O—, —N(R c )—C(O)—, —C(O)—N(R c )—, —O—C(O)—N(R c )—, —N(R c )—C(O)—N(R d )—, —C(O)—, —C(NR c )—, —O—C(O)—O—, or a bond; each of R c and R d , independently, being hydrogen, alkyl, alkenyl, alkynyl, alkoxy, hydroxylalkyl, hydroxyl, or haloalkyl; L is a straight C 3-12 hydrocarbon chain optionally containing at least one double bond, at least one triple bond, or at least one double bond and one triple bond; the hydrocarbon chain being optionally substituted with C 1-4 alkyl, C 2-4 alkenyl, C 24 alkynyl, C 1-4 alkoxy, hydroxyl, halo, amino, thio, alkylthio, arylthio, aralkylthio, acylthio, nitro, cyano, C 3-5 cycloalkyl, 3-5 membered heterocycloalkyl, monocyclic aryl, 5-6 membered heteroaryl, C 1-4 alkylcarbonyloxy, C 1-4 alkyloxycarbonyl, C 1-4 alkylcarbonyl, or formyl; and further being optionally interrupted by —O—, —N(R e )—, —N(R e )—C(O)—O—, —O—C(O)—N(R e )—, —N(R e )—C(O)—N(R f )—, or —O—C(O)—O—; each of R e and R f , independently, being hydrogen, alkyl, alkenyl, alkynyl, alkoxy, hydroxylalkyl, hydroxyl, or haloalkyl; X 1 is O or S; and each of R g , R h , and R i , independently, is hydrogen or C 1-6 alkyl; provided that when each of Y 1 and Y 2 , independently, is a bond or CH 2 , A is unsubstituted phenyl or heterocyclyl, and L is C 4-6 , L has at least one double bond or at least one triple bond; or a salt thereof.