Heterocyclylalkyl Derivatives as Novel Inhibitors of Histone Deacetylase

A compound of formula (I)

• the N-oxide forms, the pharmaceutically acceptable addition salts and the stereo-chemically isomeric forms thereof, wherein
• R1 is hydroxy or a radical of formula (a-1)
• wherein
• R2 is hydroxy or amino;
• R3 is hydrogen, thienyl, furanyl or phenyl and each thienyl, furanyl or phenyl can optionally be substituted with one or two halo, amino, nitro, cyano, hydroxy, phenyl, C1-6alkyl, (diC1-6alkyl)amino, C1-6alkyloxy, phenylC1-6alkyloxy, hydroxyC1-6alkyl, C1-6alkyloxycarbonyl, hydroxycarbonyl, C1-6alkylcarbonyl, polyhaloC1-6alkyloxy, polyhaloC1-6alkyl, C1-6alkylsulfonyl, hydroxycarbonylC1-6alkyl, C1-6alkylcarbonylamino, aminosulfonyl, aminosulfonylC1-6alkyl, isoxazolyl, aminocarbonyl, phenylC2-6alkenyl, phenylC3-6alkynyl or pyridinylC3-6alkynyl;
• R4, R5 and R6 are each independently hydrogen, amino, nitro, furanyl, halo, C1-6alkyl, C1-6alkyloxy, trifluoromethyl, thienyl, phenyl, C1-6alkylcarbonylamino, aminocarbonylC1-6alkyl or —C≡C—CH2—R7;
• wherein R7 is hydrogen, C1-6alkyl, hydroxy, amino or C1-6alkyloxy;
• X is N or CH;
• Y is O, N, NH, CH or CH2 and when Y is N or CH then the substituent is attached to the Y atom of the ring structure;
• T is O or NR8 wherein R8 is hydrogen, C1-6alkyl, C3-7cycloalkyl, hydroxyC1-6alkyl, cyanoC1-6alkyl, C1-6alkyloxyC1-6alkyl, hydroxyaminocarbonylC1-6alkyl, C1-6alkylsulfonyl, C1-6alkylcarbonyl, C1-6alkylaminocarbonyl or mono- or di(C1-6alkyl)aminosulfonyl;
• n is 0 or 1 and when n is 0 than a direct bond is intended;
• m is 1 or 2;
• p is 0 or 1 provided that when p is 0 then n is 0, —(CH2)n-(T)p- is a direct bond and Y is N;
• A is a radical selected from:
• wherein R9 is hydrogen, C1-6alkyl, C3-7cycloalkyl or C3-7cycloalkylC1-6alkyl;
• and R10 is hydrogen, hydroxy, amino, halo, cyano, C1-6alkyl, polyhaloC1-6alkyl, C1-6alkyloxycarbonyl, hydroxycarbonyl, C1-6alkylcarbonylamino, C1-6alkyloxy, or mono- or di(C1-6alkyl)amino.