Histone deacetylase inhibitors based on alpha-ketoepoxide compounds

A method of inhibiting histone deacetylation activity in hematopoietic cells ex vivo comprising contacting the cells with an effective amount of a compound, wherein the compound is of formula (I):

• wherein
• A is a cyclic moiety selected from the group consisting of C3-14 cycloalkyl, 3-14 membered heterocycloalkyl, C4-14 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 C3-12 hydrocarbon chain or an unsaturated branched C3-12 hydrocarbon chain optionally interrupted by —O—, —S—, —N(Ra)—, —C(O)—, —N(Ra)—SO2—, —SO2—N(Ra)—, —N(Ra)—C(O)—O—, —O—C(O)—N(Ra)—, —N(Ra)—C(O)—N(Rb)—, —O—C(O)—, —C(O), —O—, —O—SO2—, —SO2—O—, or —O—C(O)—O—, where each of Ra and Rb, 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 Y1 and Y2, independently, is —CH2—, —O—, —S—, —N(Rc)—, —N(Rc)—C(O)—O—, —N(Rc)—C(O)—, —C(O)—N(Rc)—, —O—C(O)—N(Rc)—, —N(Rc)—C(O)—N(Rd)—, —C(O)—, —C(NRc)—, —O—C(O)—O—, or a bond;
• each of Rc and Rd, independently, being hydrogen, alkyl, alkenyl, alkynyl, alkoxy, hydroxylalkyl, hydroxyl, or haloalkyl;
• L is a straight C3-12 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 C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-4 alkoxy, hydroxyl, halo, amino, thio, alkylthio, arylthio, aralkylthio, acylthio, nitro, cyano, C3-5 cycloalkyl, 3-5 membered heterocycloalkyl, monocyclic aryl, 5-6 membered heteroaryl, C1-4 alkylcarbonyloxy, C1-4 alkyloxycarbonyl. C1-4 alkylcarbonyl, or formyl;
• and further being optionally interrupted by —O—, —N(Re)—, —N(Re)—C(O)—O—, —O—C(O)—N(Re)—, —N(Re)—C(O)—N(Rf)—, or —O—C(O)—O—;
• each of Re and Rf, independently, being hydrogen, alkyl, alkenyl, alkenyl, alkoxy, hydroxylalkyl, hydroxyl, or haloalkyl;
• X1 is O or S;
• and
• each of Rg, Rh, and Ri, independently, is hydrogen or C1-6 alkyl;
• provided that when each of Y1 and Y2, independently, is a bond or CH2, A is unsubstituted phenyl or heterocyclyl, and L is C4-6 L has at least one double bond or at least one triple bond;
• or a salt thereof, wherein the compound is not trapoxin, thereby stimulating the hematopoietic cells.