Gem substituted hydroxamic acids

A compound of the formula

• or a pharmaceutically acceptable salt thereof, wherein
• X is oxygen;
• Z is —OR11, —NR12R13 or (C1-C6)alkyl optionally substituted with one to three substituents independently selected from the group consisting of halo, hydroxy, —CN, (C1-C6)alkyl, (C2-C6)alkenyl, (C6-C10)aryl(C2-C6)alkenyl, (C1-C9)heteroaryl(C2-C6)alkenyl, (C2-C6)alkynyl, (C6-C10)aryl(C2-C6)alkynyl, (C1-C9)heteroaryl(C2-C6)alkynyl, amino, (C1-C6)alkylamino, [(C1-C6)alkyl]2amino, mercapto, (C1-C6)alkylthio, (C1-C6)alkoxy, perfluoro(C1-C6)alkyl, perfluoro(C1-C6)alkoxy, (C6-C10)aryl, (C1-C9)heteroaryl, (C3-C9)heterocyclic, (C3-C9)cycloalkyl, (C6-C10)arylamino, (C6-C10)arylthio, (C6-C10)aryloxy, (C1-C9)heteroarylamino, (C1-C9)heteroarylthio, (C1-C9)heteroaryloxy, (C3-C9)heterocyclic-amino, (C3-C9)heterocyclic-S—, (C3-C9)heterocyclic-O—, (C3-C9)cycloalkylamino, (C3-C9)cycloalkyl-S—, (C3-C9)cycloalkyl-O—, (C1-C6)alkyl-(C═O)—, (C1-C6)alkyl-(C═O)—NH—, (C1-C6)alkyl-(C═O)—S—, (C1-C6)alkyl-(C═O)—O—, (C1-C6)alkoxy-(C═O)—, —CO2H, H2N—(C═O)—, (C1-C6)alkyl-NH—(C═O)— and [(C1-C6)alkyl]2-N—(C═O)—;
• R1, R2, R5 and R6 are each independently selected from the group consisting of hydrogen, —CN, (C1-C6)alkyl, (C2-C6)alkenyl, (C6-C10)aryl(C2-C6)alkenyl, (C1-C9)heteroaryl(C2-C6)alkenyl, (C2-C6)alkynyl, (C6-C10)aryl(C2-C6)alkynyl, (C1-C9)heteroaryl(C2-C6)alkynyl, perfluoro(C1-C6)alkyl, (C6-C10)aryl, (C1-C9)heteroaryl, (C3-C6)cycloalkyl, (C3-C9)heterocyclic, (C1-C6)alkyl(C═O)—, (C1-C6)alkoxy-(C═O)—, —CO2H, H2N—(C═O)—, (C1-C6)alkyl-NH—(C═O)— and [(C1-C6)alkyl]2-N—(C═O)—;
• wherein said R1, R2, R5 and R6 (C1-C6)alkyl groups are each independently optionally substituted by one to three groups selected from halo, trifluoromethyl, hydroxy, amino, —CN, (C1-C6)alkylthio, (C1-C6)alkoxy, (C6-C10)aryl, (C1-C9)heteroaryl, (C3-C6)cycloalkyl, (C3-C9)heterocyclic, (C6-C10)arylamino, (C6-C10)arylthio, (C6-C10)aryloxy, (C1-C9)heteroarylamino,(C1-C9)heteroarylthio, (C1-C9)heteroaryloxy, (C3-C9)heterocyclic-amino, (C3-C9)heterocyclic-S—,(C3-C9)heterocyclic-O—, (C3-C9)cycloalkylamino, (C3-C9)cycloalkyl-S—, (C3-C9)cycloalkyl-O—,(C6-C10)aryl(C1-C2)alkoxy, (C1-C9)heteroaryl(C1-C2)alkoxy, (C1-C6)alkyl-(C═O)—NH—, (C1-C6)alkyl-(C═O)—S—, (C1-C6)alkyl-(C═O)—O—, (C1-C6)alkylsulfinyl, (C6-C10)arylsulfinyl, (C1-C6)alkylsulfonyl, (C6-C10)arylsulfonyl, (C1-C6)alkylamino, or ((C1-C6)alkyl)2amino;
• R3 is hydrogen;
• (C1-C6)alkyl optionally substituted by one or more of —CN, perfluoro(C1-C6)alkyl, (C6-C10)aryl, (C3-C6)cycloalkyl, (C1-C6)alkyl(C═O)—, (C1-C6)alkoxy-(C═O)—, —CO2H, (C1-C6)alkyl-NH—(C═O)—, and [(C1-C6)alkyl]2-N—(C═O)—;
• (C6-C10)arylsulfonyl;
• (C1-C6)alkylsulfonyl;
• (C1-C6)alkyl-NH—(C═O)—;
• [(C1-C6)alkyl]2-N—(C═O)—;
• or (R10R9N)—(C═O)— wherein R9 and R10 are taken together with the nitrogen to which they are attached to form a ring selected from azetidinyl, pyrrolidinyl, piperidinyl, morpholinyl and thiomorphonyl;
• R4 is hydrogen or (C1-C4)alkyl;
• R7 and R8 are each independently selected from the group consisting of hydrogen, hydroxy, halo, —CN, (C1-C9)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, amino, (C1-C6)alkylamino, [(C1-C6)alkyl]2amino, (C1-C6)alkylthio, (C1-C6)alkoxy, perfluoro(C1-C6)alkyl, perfluoro(C1-C6)alkoxy, (C3-C6)cycloalkyl, (C6-C10)aryl, (C3-C9)heterocyclic, (C1-C9)heteroaryl, (C6-C10)arylamino, (C6-C10)arylthio, (C6-C10)aryloxy, (C1-C9)heteroarylamino, (C1-C9)heteroarylthio, (C1-C9)heteroaryloxy, (C3-C9)heterocyclic-amino, (C3-C9)heterocyclic-S—, C3-C9)heterocyclic-O—,(C3-C9)cycloalkylamino, (C3-C9)cycloalkyl-S—, (C3-C9)cycloalkyl-O—, (C1-C9)aryl(C2-C6)alkenyl, (C1-C9)heteroaryl(C2-C6)alkenyl, (C6-C10)aryl(C2-C6)alkynyl, (C1-C9)heteroaryl(C2-C6)alkynyl, (C1-C6)alkyl(C═O)—, (C1-C6)alkyl(C═O)—NH—, (C1-C6)alkyl(C═O)—S—, (C1-C6)alkyl(C═O)—O—, (C1-C6)alkoxy-(C═O)—, —CO2H, H2N—(C═O)—, (C1-C6)alkyl-NH—(C═O)— and [(C1-C9)alkyl]2-N—(C═O)—;
• wherein each of said R7 and R8 (C1-C6)alkyl group are independently optionally substituted by one to three substituents independently selected from halo, hydroxy, —CN, (C1-C6)alkoxy, (C1-C6)alkylthio, trifluoromethyl, (C3-C6)cycloalkyl, (C6-C10)aryl, (C3-C9)heterocyclic,(C1-C9)heteroaryl, (C6-C10)arylamino, (C6-C1)arylthio, (C6-C10)aryloxy, (C1-C9)heteroarylamino,(C1-C9)heteroarylthio, (C1-C9)heteroaryloxy, (C3-C9)heterocyclic-amino, (C3-C9)heterocyclic-S—,(C3-C9)heterocyclic-O—, (C3-C9)cycloalkylamino, (C3-C9)cycloalkyl-S—, (C3-C9)cycloalkyl-O—,(C6-C10)aryl(C1-C2)alkoxy, (C1-C9)heteroaryl(C1-C2)alkoxy, (C1-C6)alkyl(C═O)—NH—, (C1-C6)alkyl(C═O)—S—, (C1-C6)alkyl(C═O)—O—, (C1-C6)alkylsulfinyl, (C6-C10)arylsulfinyl, (C1-C6)alkylsulfonyl, (C6-C10)arylsulfonyl, amino, (C1-C6)alkylamino and ((C1-C6)alkyl)2amino;
• or R1 and R2, R5 and R6 or R7 and R8 may be taken together to form a carbonyl group or an optionally substituted (C3-C6)cycloalkyl ring optionally containing 1 or 2 heteroatoms;
• wherein said heteroatoms may be selected from the group consisting of —S—, —O— or >NH or >N(C1-C6)alkyl;
• and said optional substituents (i.e. 1-3 substituents per ring) may be selected from (C1-C4)alkyl, fluoro, chloro, hydroxy, (C1-C4)alkoxy and —NR14R15;
• or R5 and R7, R5 and R8, R6 and R7 or R6 and R8 may be taken together to form an optionally substituted (C4-C6)cycloalkyl ring optionally containing 1 or 2 heteroatoms;
• wherein said heteroatoms may be selected from the group consisting of —S—, —O— or >NH or >N(C1-C6)alkyl;
• and said optional substituents (i.e. 1-3 substituents) may be selected from (C1-C4)alkyl, fluoro, chloro, hydroxy, (C1-C4)alkoxy and —NR14R15;
• R11 is hydrogen, (C1-C6)alkyl, (C2-C6)alkenyl, (C6-C10)aryl(C2-C6)alkenyl, (C2-C9)heteroaryl(C2-C6)alkenyl, (C2-C6)alkynyl, (C6-C10)aryl(C2-C6)alkynyl, (C1-C9)heteroaryl(C2-C6)alkynyl, perfluoro(C1-C6)alkyl, (C6-C10)aryl, (C1-C9)heteroaryl, (C3-C6)cycloalkyl, (C3-C9)heterocyclic, (C1-C6)alkyl-(C═O)—, (C1-C6)alkoxy-(C═O)—, (C1-C6)alkyl-NH—(C═O)— and [(C1-C6) alkyl]2-N—(C═O)—;
• R12 is hydrogen, (C1-C6)alkyl, (C2-C6)alkenyl, (C1-C10)aryl(C2-C6)alkenyl, (C1-C9)heteroaryl(C2-C6)alkenyl, (C2-C6)alkynyl, (C6-C10)aryl(C2-C6)alkynyl, (C1-C9)heteroaryl(C2-C6)alkynyl, perfluoro(C1-C6)alkyl, (C6-C10)aryl, (C1-C9)heteroaryl, (C3-C6)cycloalkyl, (C3-C9)heterocyclic, (C1-C6)alkyl-(C═O)—, (C1-C6)alkoxy-(C═O)—, H2N—(C═O)—, (C1-C6)alkyl-NH—(C═O)— and [(C1-C6)alkyl]2-N—(C═O)—;
• R13 is hydrogen, (C1-C6)alkyl, (C2-C6)alkenyl, (C6-C10)aryl(C2-C6)alkenyl, (C1-C9)heteroaryl(C2-C6)alkenyl, (C2-C6)alkynyl, (C6-C10)aryl(C2-C6)alkynyl, (C1-C9)heteroaryl(C2-C6)alkynyl, perfluoro(C1-C6)alkyl, (C6-C10)aryl, (C1-C9)heteroaryl, (C3-C6)cycloalkyl or (C3-C9)heterocyclic;
• R14 is hydrogen, (C1-C6)alkyl, (C2-C6)alkenyl, (C1-C10)aryl(C2-C6)alkenyl, (C1-C9)heteroaryl(C2-C6)alkenyl, (C2-C6)alkynyl, (C6-C10)aryl(C2-C6)alkynyl, (C1-C9)heteroaryl(C2-C6)alkynyl, perfluoro(C1-C6)alkyl, (C6-C10)aryl, (C1-C9)heteroaryl, (C3-C6)cycloalkyl, (C3-C9)heterocyclic, (C1-C6)alkyl-(C═O)—, (C1-C6)alkoxy-(C═O)—, H2N—(C═O)—, (C1-C6)alkyl-NH—(C═O)— and [(C1-C6)alkyl]2-N—(C═O)—;
• R15 is hydrogen, (C1-C6)alkyl, (C2-C6)alkenyl, (C6-C10)aryl(C2-C6)alkenyl, (C1-C9)heteroaryl(C2-C6)alkenyl, (C2-C6)alkynyl, (C6-C10)aryl(C2-C6)alkynyl, (C1-C9)heteroaryl(C2-C6)alkynyl, perfluoro(C1-C6)alkyl, (C6-C10)aryl, (C1-C9)heteroaryl, (C3-C6)cycloalkyl or (C3-C9)heterocyclic;
• Q is (C1-C9)alkyl, (C6-C10)aryl, (C1-C9)heteroaryl, (C3-C9)heterocyclic, (C6-C10)aryl(C1-C6)alkyl, (C1-C9)heteroaryl(C1-C6)alkyl, (C3-C9)heterocyclic(C1-C6)alkyl, (C6-C10)aryl(C6-C10)aryl, (C6-C10)aryl(C1-C9)heteroaryl, (C6-C10)aryl(C3-C9)heterocyclic, (C1-C9)heteroaryl(C6-C10)aryl, (C1-C9)heteroaryl(C1-C9)heteroaryl, (C1-C9)heteroaryl(C3-C9)heterocyclic, (C3-C9)heterocyclic(C1-C10)aryl, (C3-C9)heterocyclic(C1-C9)heteroaryl, (C3-C9)heterocyclic(C3-C9)heterocyclic, (C6-C10)aryloxy(C1-C9)alkyl, (C6-C10)aryloxy(C6-C10)aryl, (C6-C10)aryloxy(C1-C9)heteroaryl, (C6-C10)aryloxy(C3-C9)heterocyclic, (C1-C9)heteroaryloxy(C1-C6)alkyl, (C1-C9)heteroaryloxy(C6-C10)aryl, (C1-C9)heteroaryloxy(C1-C9)heteroaryl, (C1-C9)heteroaryloxy(C3-C9)heterocyclic, (C3-C9)heterocyclic-O—(C1-C6)alkyl, (C3-C9)heterocyclic-O—(C6-C10)aryl, (C3-C9)heterocyclic-O—(C1-C9)heteroaryl, (C3-C9)heterocyclic-O—(C3-C9)heterocyclic, (C6-C10)aryl(C1-C6)alkyl(C6-C10)aryl,(C6-C10)aryl(C1-C6)alkyl(C1-C9)heteroaryl, (C6-C10)aryl(C1-C6)alkyl(C3-C9)heterocyclic, (C6-C10)aryl(C1-C6)alkoxy(C6-C10)aryl, (C6-C10)aryl(C1-C6)alkoxy(C1-C9)heteroaryl, (C6-C10)aryl(C1-C6)alkoxy(C3-C9)heterocyclic, (C6-C10)aryloxy(C1-C6)alkyl(C6-C10)aryl, (C6-C10)aryloxy(C1-C6)alkyl(C1-C9)heteroaryl, (C6-C10)aryloxy(C1-C6)alkyl(C3-C9)heterocyclic, (C1-C9)heteroaryl(C1-C6)alkyl(C6-C10)aryl, (C1-C9)heteroaryl(C1-C6)alkyl(C1-C9)heteroaryl, (C1-C9)heteroaryl(C1-C6)alkyl(C3-C9)heterocyclic, (C1-C9)heteroaryl(C1-C6)alkoxy(C6-C10)aryl, (C1-C9)heteroaryl(C1-C9)alkoxy(C1-C9)heteroaryl, (C1-C9)heteroaryl(C1-C6)alkoxy(C3-C9)heterocyclic, (C1-C9)heteroaryloxy(C1-C6)alkyl(C6-C10)aryl, (C1-C9)heteroaryloxy(C1-C6)alkyl(C1-C9)heteroaryl, (C1-C9)heteroaryloxy(C1-C6)alkyl(C3-C9)heterocyclic, (C3-C9)heterocyclic(C1-C6)alkyl(C6-C10)aryl, (C3-C9)heterocyclic(C1-C6)alkyl(C1-C9)heteroaryl, (C3-C9)heterocyclic(C1-C6)alkyl(C3-C9)heterocyclic, (C3-C9)heterocyclic(C1-C6)alkoxy(C6-C1-C9)aryl, (C3-C9)heterocyclic(C1-C6)alkoxy(C1-C9)heteroaryl, (C3-C9)heterocyclic(C1-C6)alkoxy(C3-C9)heterocyclic, (C3-C9)heterocyclic-O—(C1-C6)alkyl(C1-C10)aryl, (C3-C9)heterocyclic-O—(C1-C6)alkyl(C1-C9)heteroaryl, (C3-C9)heterocyclic-O—(C1-C6)alkyl(C3-C9)heterocyclic, (C6-C10)aryl(C6-C10)aryl(C1-C6)alkyl, (C6-C10)aryl-NH—(C1-C6)alkyl, (C6-C10)aryl-NH—(C6-C10)aryl, (C6-C10)aryl-NH—(C1-C9)heteroaryl, (C6-C10)aryl-NH—(C3-C9)heterocyclic, (C1-C9)heteroaryl-NH—(C1-C6)alkyl, (C1-C9)heteroaryl-NH—(C6-C10)aryl, (C1-C9)heteroaryl-NH—(C1-C9)heteroaryl, (C1-C9)heteroaryl-NH—(C3-C9)heterocyclic, (C3-C9)heterocyclic-NH—(C1-C6)alkyl, (C3-C9)heterocyclic-NH—(C6-C10)aryl, (C3-C9)heterocyclic-NH—(C1-C9)heteroaryl, (C3-C9)heterocyclic-NH—(C3-C9)heterocyclic, (C6-C10)aryl(C1-C6)alkyl-NH—(C6-C10)aryl, (C6-C10)aryl(C1-C6)alkyl-NH—(C1-C9)heteroaryl, (C6-C10)aryl(C1-C6)alkyl-NH—(C3-C9)heterocyclic, (C6-C10)aryl-NH—(C1-C6)alkyl(C6-C10)aryl, (C6-C10)aryl-NH—(C1-C6)alkyl(C1-C9)heteroaryl, (C6-C10)aryl-NH—(C1-C6)alkyl(C3-C9)heterocyclic, (C1-C9)heteroaryl(C1-C9)alkyl-NH—(C6-C10)aryl, (C1-C9)heteroaryl(C1-C6)alkyl-NH—(C1-C9)heteroaryl, (C1-C9)heteroaryl(C1-C6)alkyl-NH—(C3-C9)heterocyclic, (C1-C9)heteroaryl-NH—(C1-C6)alkyl(C6-C10)aryl, (C1-C9)heteroaryl-NH—(C1-C6)alkyl(C1-C9)heteroaryl, (C1-C9)heteroaryl-NH—(C1-C6)alkyl(C3-C9)heterocyclic, (C3-C9)heterocyclic(C1-C6)alkyl-NH—(C6-C10)aryl, (C3-C9)heterocyclic(C1-C6)alkyl-NH—(C1-C9)heteroaryl, (C3-C9)heterocyclic(C1-C6)alkyl-NH—(C3-C9)heterocyclic, (C3-C9)heterocyclic-NH—(C1-C6)alkyl(C6-C10)aryl, (C3-C9)heterocyclic-NH—(C1-C6)alkyl(C1-C9)heteroaryl, (C3-C9)heterocyclic-NH—(C1-C6)alkyl(C3-C9)heterocyclic, (C6-C10)aryl(C1-C6)alkyl-NH—(C1-C6)alkyl or (C6-C10)aryl(C1-C6)alkoxy(C1-C6)alkyl, wherein each of said (C6-C10)aryl, (C1-C9)heteroaryl or (C3-C9)heterocyclic groups may optionally be substituted by one or more substituents, independently selected from the group consisting of halo, —CN, (C1-C6)alkyl optionally substituted with one or more fluorine atoms, hydroxy, hydroxy-(C1-C6)alkyl, (C1-C6)alkoxy optionally substituted with one or more fluorine atoms, (C1-C6)alkoxy(C1-C6)alkyl, HO—(C═O)—,(C1-C6)alkyl-O—(C═O)—, HO—(C═O)—(C1-C6)alkyl, (C1-C6)alkyl-O—(C═O)—(C1-C6)alkyl, (C1-C6)alkyl-(C═O)—O—,(C1-C6)alkyl-(C═O)—O—(C1-C6)alkyl, H(O═C)—, H(O═C)—(C1-C6)alkyl, (C1-C6)alkyl(O═C)—, (C1-C9)alkyl(O═C)—(C1-C6)alkyl, NO2, amino, (C1-C6)alkylamino, [(C1-C9)alkyl]2amino, amino(C1-C6)alkyl, (C1-C6)alkylamino(C1-C6)alkyl, [(C1-C6)alkyl]2amino(C1-C6)alkyl, H2N—(C═O)—, (C1-C6)alkyl-NH—(C═O)—, [(C1-C6)alkyl]2N—(C═O)—, H2N(C═O)—(C1-C6)alkyl, (C1-C6)alkyl-HN(C═O)—(C1-C6)alkyl, [(C1-C6)alkyl]2N—(C═O)—(C1-C9)alkyl, H(O═C)—NH—, (C1-C6)alkyl(C═O)—NH, (C1-C6)alkyl(C═O)— [NH](C1-C6)alkyl, (C1-C6)alkyl(C═O)— [N(C1-C6)alkyl](C1-C6)alkyl, (C1-C6)alkyl-S—(C1-C6)alkyl-(S═O)—, (C1-C6)alkyl-SO2—, (C1-C6)alkyl-SO2—NH—, (C1-C6)alkyl-SO2-[N—(C1-C6)alkyl]-, H2N—SO2—, H2N—SO2—(C1-C6)alkyl, (C1-C6)alkyl HN—SO2—(C1-C6)alkyl, [(C1-C9)alkyl]2N—SO2—(C1-C9)alkyl, CF3SO2—, (C1-C6)alkyl-SO2—, phenyl, phenyl(C1-C9)alkyl, (C3-C10)cycloalkyl, (C1-C9)heterocycloalkyl, and (C1-C9)heteroaryl.