Spirocyclic derivatives as histone deacetylase inhibitors

Compounds of formula (I)

• wherein:
• m, n are independently zero or an integer from 1 to 4;
• p is, zero or an integer from 1 to 3;
• R is hydrogen;
• C1-C6 alkyl, optionally substituted by C3-C8 cycloalkyl, C6-C10 aryl, or hetero(C2-C9)aryl;
• (CO)R2;
• (SO2)R3;
• C3-C8 cycloalkyl;
• C6-C10 aryl or hetero(C2-C9)aryl;
• R1 is halogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, or C1-C6 haloalkoxy;
• Y is CH2 or NR4;
• Z is C═R5;
• R2 is C1-C6 alkyl, optionally substituted by C6-C10 aryl or by hetero(C2-C9)aryl;
• C6-C10 aryl;
• hetero(C2-C9)aryl;
• O—C1-C6 alkyl, optionally substituted by C6-C10 aryl;
• O—(C6-C10-aryl) or NR6R7;
• R3 is C1-C6 alkyl, optionally substituted by C6-C10 aryl or by hetero(C2-C9)aryl;
• C6-C10 aryl or hetero(C2-C9)aryl;
• R4 is hydrogen;
• C1-C6 alkyl, optionally substituted by C6-C10 aryl or by hetero(C2-C9)aryl;
• R5 is oxygen or NOR8;
• R6 is hydrogen;
• C1-C6 alkyl, optionally substituted by C6-C10 aryl or by hetero(C2-C9)aryl;
• C6-C10 aryl or hetero(C2-C9)aryl;
• R7 is hydrogen;
• C1-C6 alkyl, optionally substituted by C6-C10 aryl or by hetero(C2-C9)aryl;
• or R6 and R7 together with the nitrogen to which they are bound form a C4-C9-heterocyclic ring, optionally containing one or more further heteroatoms in the ring selected from NR9, O or S;
• R8 is hydrogen;
• C1-C6 alkyl, optionally substituted by C6-C10 aryl;
• R9 is hydrogen;
• C1-C6 alkyl, optionally substituted by C6-C10 aryl or by hetero(C2-C9)aryl;
• C6-C10 aryl;
• hetero(C2-C9)aryl;
• (CO)R10;
• or (SO2)R11;
• R10 is C1-C6 alkyl, optionally substituted by C6-C10 aryl or by hetero(C2-C9)aryl;
• O—C1-C6 alkyl, optionally substituted by C6-C10 aryl;
• O—(C6-C10-aryl) or NR12R13;
• R11 is C1-C6 alkyl, optionally substituted by C6-C10 aryl or by hetero(C2-C9)aryl;
• C6-C10 aryl or hetero(C2-C9)aryl;
• R12 is hydrogen;
• C1-C6 alkyl, optionally substituted by C6-C10 aryl or by hetero(C2-C9)aryl;
• C6-C10 aryl or hetero(C2-C9)aryl;
• R13 is hydrogen;
• C1-C6 alkyl, optionally substituted by C6-C10 aryl or hetero(C2-C9)aryl;
• and the pharmaceutically acceptable salts thereof;
• provided that when p is zero, then n and m cannot be both 1.