Pyridothiophene Compounds

A method of inhibiting HSP90 activity in mammals which method comprises administering to the mammal an amount of a compound of formula (I), or a salt or N-oxide thereof, effective to inhibit said HSP90 activity:

• wherein
• R2 is a group of formula (IA):
• —(Ar1)m-(Alk1)p-(Z)r-(Alk2)s-Q (IA)
• wherein in any compatible combination
• Ar1 is an optionally substituted aryl or heteroaryl radical,
• Alk1 and Alk2 are optionally substituted divalent C1-C3 alkylene or C2-C3 alkenylene radicals,
• m, p, r and s are independently 0 or 1,
• Z is —O—, —S—, —(C═O)—, —(C═S)—SO2—, —C(═O)O—, —C(═O)NRA—, —C(═S)NRA—, —SO2NRA—, —NRAC(═O)—, —NRASO2— or —NRA—
• wherein RA is hydrogen or C1-C6 alkyl, and
• Q is hydrogen or an optionally substituted carbocyclic or heterocyclic radical;
• R3 is hydrogen, an optional substituent, or an optionally substituted (C1C6)alkyl, aryl or heteroaryl radical;
• and
• R4 is a carboxamide or sulfonamide group,
• wherein the optional substituent is selected from the group consisting of:
• C1-C6 alkyl, C1-C6 alkoxy, hydroxyl, hydroxy C1-C6 alkyl, mercapto, mercapto C1-C6 alkyl, C1-C6 alkylthio, halo, trifluoromethyl, trifluoromethoxy, nitro, nitrile (—CN), oxo, phenyl, —COOH, COORC, —CORC, —SO2RC, —CONH2, —SO2NH2, —CONHRC, —SO2NHRC, —CONRCRD, —SO2NRCRD, —NH2, —NHRC, —NRCRD, —OCONH2, —OCONHRC, —OCONRCRD, —NHCORC, —NHCOORC, —NHRDCOORC, —NHSO2ORC, —NRDSO2ORC, —NHCONH2, —NRCCONH2, —NHCONHRD, —NRCCONHRD, —NHCONHRCRD, and —NRCCONRCRD, wherein RC and RD are independently C1-C6 alkyl groups.

A pharmaceutical or veterinary composition comprising a compound of formula (I), or a salt or N-oxide thereof:

• wherein
• R2 is a group of formula (IA):
• —(Ar1)m-(Alk1)p-(Z)r-(Alk2)s-Q (IA)
• wherein in any compatible combination
• Ar1 is an optionally substituted aryl or heteroaryl radical,
• Alk1 and Alk2 are optionally substituted divalent C1-C3 alkylene or C2-C3 alkenylene radicals,
• m, p, r and s are independently 0 or 1,
• Z is —O—, —S—, —(C═O)—, —(C═S)—SO2—, —C(═O)O—, —C(═O)NRA—, —C(═S)NRA—, —SO2NRA—, —NRAC(═O)—, —NRASO2— or —NRA—
• wherein RA is hydrogen or C1-C6 alkyl, and
• Q is hydrogen or an optionally substituted carbocyclic or heterocyclic radical;
• R3 is hydrogen, an optional substituent, or an optionally substituted (C1C6)alkyl, aryl or heteroaryl radical;
• and
• R4 is a carboxamide or sulfonamide group,
• wherein the optional substituent is selected from the group consisting of:
• C1-C6 alkyl, C1-C6 alkoxy, hydroxyl, hydroxy C1-C6 alkyl, mercapto, mercapto C1-C6 alkyl, C1-C6 alkylthio, halo, trifluoromethyl, trifluoromethoxy, nitro, nitrile (—CN), oxo, phenyl, —COOH, COORC, —CORC, —SO2RC, —CONH2—SO2NH2, —CONHRC, —SO2NHRC, —CONRCRD, —SO2NRCRD, —NH2, —NHRC, —NRCRD, —OCONH2, —OCONHRC, —OCONRCRD, —NHCORC, —NHCOORC, —NHRDCOORC, —NHSO2ORC, —NRDSO2ORC, —NHCONH2, —NRCCONH2, —NHCONHRD, —NRCCONHRD, —NHCONHRCRD, and —NRCCONRCRD, wherein RC and RD are independently C1-C6 alkyl groups,
• in an amount effective to inhibit said HSP90 activity together with a pharmaceutically or veterinarily acceptable carrier.