Histone deacetylase inhibitors

A method of inhibiting histone deacetylase in cells comprising contacting the cells with an effective amount of a compound of formula (I):

• 4
• wherein
• A is phenyl optionally substituted with alkyl, alkenyl, alkynyl, alkoxy, hydroxyl, hydroxylalkyl, halo, haloalkyl, or amino;
• each of Y1 and Y2, independently, is —CH2—, —O—, —S—, —N(Rc)—, or a bond;
• where Rc is hydrogen, alkyl, alkenyl, alkynyl, alkoxy, hydroxylalkyl, hydroxyl, or haloalkyl;
• L is a straight C2-12 hydrocarbon chain optionally containing at least one double bond, at least one triple bond, or at least one double bond and one triple bond;
• said hydrocarbon chain being optionally substituted with C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-4 alkoxy, hydroxyl, halo, amino, 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, alkynyl, alkoxy, hydroxylalkyl, hydroxyl, or haloalkyl;
• X1 is O or S;
• and
• X2 is —OR1, —SR1, —NR3—OR1, —NR3—SR1, —C(O)—OR1, —CHR4—OR1, —N═N—C(O)—N(R3)2, or —O—CHR4—O—C(O)—R5;
• where each of R1 and R2, independently, is hydrogen, alkyl, hydroxylalkyl, haloalkyl, or a hydroxyl protecting group;
• R3 is hydrogen, alkyl, alkenyl, alkynyl, alkoxy, hydroxylalkyl, hydroxyl, haloalkyl, or an amino protecting group;
• R4 is hydrogen, alkyl, hydroxylalkyl, or haloalkyl;
• R5 is alkyl, hydroxylalkyl, or haloalkyl;
• and provided that when L is a C2-3 hydrocarbon containing no double bonds and X2 is —OR1, Y1 is not a bond and Y2 is not a bond;
• or a salt thereof;
• and
• determining whether the level of acetylated histones in the treated cells is higher than in untreated cells under the same conditions.