Heterocycle Substituted Amide and Sulfur Amide Derivatives as Histone Deacetylase (HDAC) Inhibitors

A method for the treatment or prevention of neurodegenerative diseases schizophrenia, stroke, mental retardation, immune disorders or asthma comprising the step of administering a therapeutically effective amount of a compound to a subject, wherein the compound is of formula I a compound of formula I:

• wherein:
• p is 0, 1, 2 or 3;
• q is 1,2, 3 or 4;
• t is 0 or 1;
• X is C or S═O;
• Y is R2, (C═S)R2, (C═O)R2, (C═S)NRxR2 or (C═O)NRxR2;
• Het is a 5 membered unsaturated heterocycle containing 1, 2, 3 or 4 heteroatoms independently selected from N, O and S, but not more than one of which is O or S, or a 6 membered unsaturated heterocycle containing 1, 2, 3 or 4 heteroatoms independently selected from N and O;
• optionally substituted by one or more groups independently chosen from cyano, halogen, hydroxy, oxido, oxo, nitro, amino, C1-6alkylamino, di(C1-6alkyl)amino, C1-6alkyl, haloC1-6alkyl, C1-6alkoxy, haloC1-6alkoxy, C3-10cycloalkyl, C2-6alkenyl, C2-6alkynyl and C6-10aryl;
• R1 is hydrogen, C1-6alkyl, haloC1-6alkyl, C6-10aryl, 5 membered unsaturated heterocycle containing 1, 2, 3 or 4 heteroatoms independently selected from O, N and S, but not more than one of which is O or S, 6 membered unsaturated heterocycle containing 1, 2 or 3 nitrogen atoms, or 8-10 membered unsaturated or partially saturated heterocycle containing heteroatoms independently selected from O, N and S;
• any of which rings being optionally substituted by one or more groups independently chosen from cyano, halogen, nitro, oxo, hydroxy, oxido, C1-6alkyl, haloC1-6alkyl, C1-6alkoxy, haloC1-6alkoxy, C1-6alkylcarbonyl, C6-10aryl, C6-10aryloxy, C6-10arylcarbonyl, N(Ra)2, SO2N(Rb)2 and N(Rb)SO2Rb;
• R2 is R9 or R10;
• R3 is hydrogen, halogen, hydroxy, cyano, C1-6alkyl, haloC1-6alkyl, hydroxyC1-6alkyl, C1-6alkoxy, haloC1-6alkoxy, C3-10cycloalkyl, haloC3-10cycloalkyl, C2-10alkenyl, C2-10alkynyl, nitro, N(Rc)2, C6-10aryl, C6-10arylC1-6alkyl, C6-10arylC1-6alkoxy;
• 4, 5 or 6 membered saturated or partially saturated heterocycle containing 1, 2 or 3 heteroatoms independently selected from N, O and S, optionally bridged by a C1-6alkyl group;
• 5 membered unsaturated heterocycle containing 1, 2, 3 or 4 heteroatoms independently selected from N, O and S, but not more than one of which is O or S;
• 6 membered unsaturated heterocycle containing 1, 2 or 3 nitrogen atoms;
• or a 7-13 membered saturated, partially saturated or unsaturated heterocycle containing heteroatoms independently selected from N, O or S;
• any of which rings being optionally substituted by one or more groups independently chosen from Rd;
• R4, R5 and R7 are independently selected from hydrogen and C1-6alkyl;
• R6 and R8 are independently hydrogen, C1-6alkyl, a 5 or 6 membered saturated or partially saturated heterocycle containing 1, 2 or 3 heteroatoms independently selected from N, O and S or a 6 membered unsaturated heterocycle containing 1, 2 or 3 nitrogen atoms;
• each of which rings being optionally substituted by one or more groups independently chosen from halogen, nitro, amino, cyano, oxo, hydroxy, C1-6alkyl, haloC1-6alkyl, C1-6alkoxy, haloC1-6alkoxy, C3-10cycloalkyl, C2-6alkenyl and C2-6alkynyl;
• or
• R6 and R8 together represent an oxo group;
• R9 is hydrogen, hydroxy, C1-6alkyl, haloC1-6alkyl or C1-6alkoxy;
• R10 is C6-10aryl, C6-10arylC1-6alkyl, a 5 membered unsaturated heterocycle containing 1, 2, 3 or 4 heteroatoms independently selected from N, O and S, but not more than one of which is O or S, or a 6 membered unsaturated heterocycle containing 1, 2, or 3 heteroatoms independently selected from N and O;
• optionally substituted by one or more groups independently chosen from cyano, halogen, hydroxy, oxo, oxido, nitro, N(Rc)2, C1-6alkyl, haloC1-6alkyl, C1-6alkoxy, haloC1-6alkoxy, C3-10cycloalkyl, C2-6alkenyl, C2-6alkynyl, CON(Rb)2, NRbCORb, SO2N(Rb)2, NRbSO2Rb, C6-10aryl, 5 or 6 membered saturated or partially saturated heterocycle containing 1, 2 or 3 heteroatoms independently selected from N, O and S, 5 membered unsaturated heterocycle containing 1, 2, 3 or 4 heteroatoms independently selected from N, O and S, but not more than one of which is O or S, 6 membered unsaturated heterocycle containing 1, 2 or 3 nitrogen atoms and a 7-10 membered saturated, partially saturated or unsaturated heterocycle containing heteroatoms independently selected from N, O or S;
• each Ra is independently selected from hydrogen, C1-6alkyl, C6-10aryl, C1-6alkylcarbonyl and C6-10arylcarbonyl;
• each Rb is independently hydrogen, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C6-10aryl, 5 or 6 membered saturated or partially saturated heterocycle containing 1, 2 or 3 heteroatoms independently selected from N, O or S, optionally bridged by a C1-6alkyl group;
• 5 membered unsaturated heterocycle containing 1, 2, 3 or 4 heteroatoms independently selected from N, O and S, but not more than one of which is O or S;
• or a 6 membered unsaturated heterocycle containing 1, 2 or 3 nitrogen atoms;
• any of which rings may be optionally substituted by one or more groups independently chosen from halogen, hydroxy, amino, cyano, C1-6alkyl, haloC1-6alkyl, C1-6alkoxy and haloC1-6alkoxy;
• each Rc is independently selected from hydrogen and C1-6alkyl;
• each Rd is halogen, hydroxy, cyano, C1-6alkyl, haloC1-6alkyl, haloC1-6alkylcarbonyl, haloC1-6alkylcarbonyloxy, C1-6alkoxy, haloC1-6alkoxy, carboxy, C1-6alkylcarbonyl, C1-6alkoxycarbonyl, nitro, oxo, SO2N(Re)2, NReSO2Re, N(R)2, C6-10aryl, C6-10arylC1-6alkyl, 5 or 6 membered saturated or partially saturated heterocycle containing 1, 2 or 3 heteroatoms independently selected from N, O or S, optionally bridged by a C1-6alkyl group;
• 5 membered unsaturated heterocycle containing 1, 2, 3 or 4 heteroatoms independently selected from N, O and S, but not more than one of which is O or S;
• or a 6 membered unsaturated heterocycle containing 1, 2 or 3 nitrogen atoms;
• any of which rings may be optionally substituted by one or more groups independently chosen from halogen, hydroxy, amino, cyano, C1-6alkyl, haloC1-6alkyl, C1-6alkoxy and haloC1-6alkoxy;
• each Re is independently hydrogen, C1-6alkyl, C1-6alkylcarbonyl, carboxy or C1-6alkyloxycarbonyl;
• and
• each Rx is independently selected from hydrogen and C1-6alkyl;
• or a pharmaceutically acceptable salt, stereoisomer or tautomer thereof.