N-sulfonylpiperidines as metalloproteinase inhibitors (tace)

A compound of formula (1):

• Z is selected from —CONR15OH and —N(OH)CHO;
• R15 is hydrogen or C1-3alkyl;
• R1 is hydrogen or a group selected from C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-7cycloalkyl, C5-7cycloalkenyl, aryl and heteroaryl where the group is optionally substituted by one or more substituents independently selected from halo, nitro, cyano, trifluoromethyl, trifluoromethyloxy, C1-4alkyl, C2-4alkenyl, C2-4alkynyl, C3-6cycloalkyl (optionally substituted by one or more R17), aryl (optionally substituted by one or more R17), heteroaryl (optionally substituted by one or more R17), heterocyclyl, C1-4alkoxycarbonyl, —OR5, —SR2, —SOR2, —SO2R2, —COR2, —CO2R5, —CONR5R, —NR16COR5, —SO2NR5R6 and —NR16SO2R2;
• R16 is hydrogen or C1-3alkyl;
• R17 is selected from halo, nitro, cyano, trifluoromethyl, trifluoromethoxy, C1-6alkyl, C3-6cycloalkyl and C1-6alkoxy;
• R2 is group selected from C1-6alkyl, C3-6cycloalkyl, C5-7cycloalkenyl, heterocycloalkyl, aryl, heteroaryl, arylC1-4alkyl and heteroarylC1-4alkyl where the group is optionally substituted by one or more halo;
• R5 is hydrogen or a group selected from C1-6alkyl, C3-6cycloalkyl, C5-7cycloalkenyl, heterocycloalkyl, aryl, heteroaryl, arylC1-4alkyl and heteroarylC1-4alkyl where the group is optionally substituted by one or more halo;
• R6 is hydrogen, C1-6alkyl or C3-6cycloalkyl;
• or R5 and R6 together with the nitrogen to which they are attached form a heterocyclic 4- to 7-membered ring;
• R5 is hydrogen or a group selected from C1-6alkyl, C3-7cycloalkyl and C5-7cycloalkenyl where the group is optionally substituted by one or more substituents independently selected from halo, nitro, cyano, trifluoromethyl, trifluoromethyloxy and C1-4alkyl;
• R3 and R4 are both hydrogen;
• n is 0 or 1;
• m is 0 or 1;
• D is hydrogen, C1-4alkyl, C3-6cycloalkyl or fluoro;
• X is —(CR9R10)t-Q-(CR11R12)u— where t and u are independently 0 or 1 with the proviso that t and u cannot both be 0;
• Q is O, S, SO or SO2;
• R9, R10, R11 and R12 are independently selected from hydrogen, C1-4alkyl and C3-6cycloalkyl;
• B is a group selected from aryl, heteroaryl, heterocyclyl, C3-10cycloalkyl and C5-7cycloalkenyl where each group is optionally substituted by one or more groups independently selected from nitro, trifluoromethyl, trifluoromethyloxy, halo, C1-4alkyl (optionally substituted by one or more R13), C2-4alkenyl, C2-4alkynyl, C3-6cycloalkyl (optionally substituted by one or more R13), heterocycloalkyl, heteroaryl, aryl, —OR13, cyano, —NR13R14, —CONR13R14, —NR16COR13, —SO2NR13R14, —NR16SO2R13, —SR13, —SOR7 and —SO2R7;
• R7 is C1-6alkyl or C3-6cycloalkyl
• R13 and R14 are independently hydrogen, C1-6alkyl or C3-6cycloalkyl;
• or R13 and R14 together with the nitrogen to which they are attached form a heterocyclic 4 to 7-membered ring.
• or a pharmaceutically acceptable salt or an in vivo hydrolysable ester thereof.