ArylSulfonamide Based Matrix Metalloprotease Inhibitors

A method of treating a disorder or a disease in a subject mediated by MMP-2, and/or MMP-8, and/or MMP-9, and/or MMP-12 and/or MMP-13, comprising:

• administering to the subject a therapeutically effective amount of a compound of formula (II)
• wherein R′1 is selected from hydrogen, alkyl, alkoxy, cycloakyl, R4—O—, R5C(O)—, R6SO2—, (R7)NH—C(O)—, and (R8)(R9)N—, aryl, heteroaryl, heterocycloalkyl, said aryl, heteroaryl, and heterocycloalkyl are optionally substituted by one or two substituents selected from hydroxy, halo, alkyl, carboxyl, alkoxycarbonyl, and HC(O)—;
• wherein R4, R5, R6, R7, R8 and R9 are independently alkyl or aryl each of which is optionally substituted by one to five substituents selected from the group consisting of (C1-C7) alkyl, halo, hydroxyl, (C1-C7) alkoxy, and aryl;
• R2 and R3 are independently hydrogen, or (C1-C7) alkyl;
• X is selected from hydrogen, cyano, halogen, nitro, alkyl-S—, alkyl-SO—, alkyl-SO2—, H2N—SO2—, R5—C(O)—, alkyl, and R4—O, wherein R4 and R5 are independently alkyl or aryl each of which is optionally substituted by csubstituents selected from the group consisting of (C1-C7) alkyl, halo, hydroxyl, (C1-C7) alkoxy, and aryl;
• or
• a pharmaceutically acceptable salt thereof, or an optical isomer thereof;
• or a mixture of optical isomers.

A method of treating a disorder or a disease in a subject mediated by MMP-2, and/or MMP-8, and/or MMP-9, and/or MMP-12 and/or MMP-13, comprising:

• administering to the subject a therapeutically effective amount of a compound of formula (III)
• wherein R′1 is selected from hydrogen, alkyl, cycloakyl, R5C(O)—, R6SO2—, (R7)NH—C(O)—, of and (R8)(R9)N—, aryl, heteroaryl, heterocycloalkyl, said aryl, heteroaryl, and heterocycloalkyl are optionally substituted by one or two substituents selected from alkyl-SO2—, alkyl-C(O)—, heterocycloalkyl-alkyl-, alkyl-alkoxy-, alkoxy-, alkyl, aryl, cycloalkyl, halo, alkoxy-alkyl-, alkyl-O—C(O)—, cycloalkyl-alkyl-, dialkylamino-alkoxy-, and dialkylamino-alkyl-;
• wherein R5, R6, R7, R8 and R9 are independently alkyl or aryl, each of which is optionally substituted by one to five substituents selected from the group consisting of (C1-C7) alkyl, halo, hydroxy, (C1-C7) alkoxy, and aryl;
• R2 and R3 are hydrogen;
• X is selected from hydrogen, cyano, halogen, nitro, alkyl-S—, alkyl-SO—, alkyl-SO2—, H2N—SO2—, R5—C(O)—, alkyl, and R4—O, wherein R4 and R5 are independently alkyl or aryl each of which is optionally substituted by substituents selected from the group consisting of (C1-C7) alkyl, halo, hydroxy, (C1-C7) alkoxy, and aryl;
• Y is C or N;
• or
• a pharmaceutically acceptable salt thereof, or an optical isomer thereof;
• or a mixture of optical isomers.