Pyridine and pyrimidine derivatives as 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
• n is 0 or 1 and when n is 0 than a direct bond is intended;
• p is 0 or 1 provided that when p is 0 then n is 0, —(CH2)n—(NR3)p— is a direct bond and Y is N;
• each X is independently N or CH;
• each Y is independently 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;
• R1 is hydroxy or a radical of formula (a-1)
• wherein
• R4 is hydroxy or —NH2;
• R5 is hydrogen, thienyl, furanyl or phenyl and each thienyl, furanyl or phenyl can optionally be substituted with 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;
• R6, R7 and R8 are each independently hydrogen, —NH2, nitro, furanyl, halo,
• C1-6alkyl, C1-6alkyloxy, trifluoromethyl, thienyl, phenyl, C1-6alkylcarbonylamino, aminocarbonylC1-6alkyl or —C≡C—CH2—R9;
• wherein R9 is hydrogen, C1-6alkyl, hydroxy, amino or C1-6alkyloxy;
• R2 is CH2OH, CH2CH(OH)—CH2OH, CH2OCH3 or CH2OCH2CH3;
• R3 is hydrogen, C1-6alkyl, C3-7cycloalkyl, C1-6alkylcarbonyl or C1-6alkylsulfonyl;
• and
• Z is a radical of formula:
• wherein R10 is hydrogen, C1-6alkyl, C3-7cycloalkyl or phenylsulfonyl;
• and
• R11 is hydrogen, hydroxy, amino, halo, C1-6alkyl, polyhaloC1-6alkyl, C1-6alkylcarbonyl, cyano, hydroxycarbonyl, C1-6alkylcarbonylamino, C1-6alkyloxy, or mono- or di(C1-6alkyl)amino.