Matrix metalloproteinase inhibitors

A method for treating chronic obstructive pulmonary disease (COPD), which comprises administering an effective amount of a compound of formula (Ic) to a human subject in need thereof:

• wherein:
• A represents bond, —C1-6alkyl or —CH═CH—C1-4alkyl;
• B represents bond, —O—, —S—, —SO—, —SO2—, —CO—, —CR7R8, —CO2R14, —CONR14R15, —N(COR14)(COR15), —N(SO2R14)(COR15), or —NR14R15;
• wherein:
• R7 and R8 each independently represent H, halo, C1-6 alkyl or C1-4 alkylaryl;
• R14 and R15 each independently represent H, C1-6 alkyl, C1-4 alkylaryl or C1-4 alkylheteroaryl or together with the functionality to which they are attached R14 and R15 form a heterocyclic or fused heterocyclic group which contain one or more further atoms selected from C, O, N or S;
• D represents bond, or —C1-6 alkyl;
• E represents substituted aryl or substituted or unsubstituted heteroaryl;
• wherein heteroaryl is selected from mono- or bicyclic heterocyclic aromatic containing 1-3 hetero atoms selected from nitrogen, oxygen and sulphur;
• wherein aryl or heteroaryl is substituted by one or more substituents selected from C1-6 alkyl, C2-6 alkenyl, halogen, C1-6 alkoxy, cyano, hydroxy, nitro, amino, —N(CH3)2, —NHCOC1-6 alkyl, —OCF3, —CF3, —COOC1-6 alkyl, —OCHCF2, —SCF, —CONR5R6, —SO2N(CH3)2, —SO2CH3 or —SCH3 groups, or unsubstituted or substituted fused cycloalkyl or heterocyclic rings;
• wherein fused cycloalkyl or heterocyclic rings optionally are substituted by carbonyl groups;
• wherein R5 and R6 each independently represent H, C1-6 alkyl or C1-4 alkylaryl;
• R18 represents halo, cyano, nitro, —OR16, —SR16, —COR16, —NR17COR16, —CONR16R17, optionally substituted phenoxy or —C1-6alkyl optionally substituted by —OR16;
• wherein:
• R16 represents H, —C1-6 alkyl or —C1-4 alkylaryl;
• R17 represents H or —C1-6 alkyl;
• m and n each independently represents 0 or an integer 1, 2 or 3;
• or
• a pharmaceutically acceptable salt thereof.

A method for treating chronic obstructive pulmonary disease (COPD), which comprises administering an effective amount of a compound of formula (Id) to a human subject in need thereof:

• wherein:
• R20 represents a substituted or unsubstituted aryl or heteroaryl group selected from phenyl, benzofuraryl and pyrimidinyl;
• and
• represents a substituted aryl or a substituted or unsubstituted heteroaryl group comprising at least one nitrogen atom;
• wherein heteroaryl is selected from mono- or bicyclic heterocyclic aromatic containing 1-3 hetero atoms selected from nitrogen, oxygen and sulphur;
• wherein aryl or heteroaryl is substituted by one or more substituents selected from C1-6 alkyl, C2-6 alkenyl, halogen, C1-6 alkoxy, cyano, hydroxy, nitro, amino, —N(CH3)2, —NHCOC1-6 alkyl, —OCF3, —CF3, —COOC1-6 alkyl, —OCHCF2, —SCF3, —CONR5R6, —SO2N(CH3)2, —SO2CH3 or —SCH3 groups, or unsubstituted or substituted fused cycloalkyl or heterocyclic rings;
• wherein fused cycloalkyl or heterocyclic rings optionally are substituted by carbonyl groups;
• wherein R5 and R6 each independently represent H, C1-6 alkyl or C1-4 alkylaryl;
• or
• a pharmaceutically acceptable salt thereof.

A method for treating idiopathic pulmonary fibrosis, which comprises administering to a human subject in need thereof an effective amount of a compound of formula (Ia) or (Ib):

• wherein:
• T is absent or represents —O—, —S—, —NR16 or —CR16R17;
• --- represents optional bonds;
• G1 and G2 each independently represents —CH— or —N—;
• A represents bond, —C1-6alkyl or —CH═CH—C1-4alkyl;
• B represents bond, —O—, —S—, —SO—, —SO2—, —CO—, —CR7R8, —CO2R14, —CONR14R15, —N(COR14)(COR15), —N(SO2R14)(COR15), or —NR14R15;
• wherein:
• R7 and R8 each independently represent H, halo, C1-6 alkyl or C1-4 alkylaryl;
• R14 and R15 each independently represent H, C1-6 alkyl, C1-4 alkylaryl or C1-4 alkylheteroaryl or together with the functionality to which they are attached R14 and R15 form a heterocyclic or fused heterocyclic group which contain one or more further atoms selected from C, O, N or S;
• D represents bond, or —C1-6 alkyl;
• E represents substituted aryl or substituted or unsubstituted heteroaryl;
• wherein heteroaryl is selected from mono- or bicyclic heterocyclic aromatic containing 1-3 hetero atoms selected from nitrogen, oxygen and sulphur;
• wherein aryl or heteroaryl is substituted by one or more substituents selected from C1-6 alkyl, C2-6 alkenyl, halogen, C1-6 alkoxy, cyano, hydroxy, nitro, amino, —N(CH3)2, —NHCOC1-6 alkyl, —OCF3, —CF3, —COOC1-6 alkyl, —OCHCF2, —SCF3, —CONR5R6, —SO2N(CH3)2, —SO2CH3 or —SCH3 groups, or unsubstituted or substituted fused cycloalkyl or heterocyclic rings;
• wherein fused cycloalkyl or heterocyclic rings optionally are substituted by carbonyl groups;
• wherein R5 and R6 each independently represent H, C1-6 alkyl or C1-4 alkylaryl;
• R18 and R19 each independently represents halo, cyano, nitro, —OR16, —SR16, —COR16, —NR17COR16, —CONR16R17, optionally substituted phenoxy or —C1-6alkyl optionally substituted by —OR16;
• wherein:
• R16 represents H, —C1-6 alkyl or —C1-4 alkylaryl;
• R17 represents H or —C1-6 alkyl;
• m and n each independently represents 0 or an integer 1, 2 or 3;
• or
• a pharmaceutically acceptable salt thereof.

A method for treating idiopathic pulmonary fibrosis, which comprises administering to a human subject in need thereof an effective amount of a compound of formula (Ic):

• wherein:
• A represents bond, —C1-6alkyl or —CH═CH—C1-4alkyl;
• B represents bond, —O—, —S—, —SO—, —SO2—, —CO—, —CR7R8, —CO2R14, —CONR14R15, —N(COR14)(COR15), —N(SO2R14)(COR15), or —NR14R15;
• wherein R7 and R8 each independently represent H, halo, C1-6 alkyl or C1-4 alkylaryl;
• wherein R14 and R15 each independently represent H, C1-6 alkyl, C1-4 alkylaryl or C1-4 alkylheteroaryl or together with the functionality to which they are attached R14 and R15 form a heterocyclic or fused heterocyclic group which contain one or more further atoms selected from C, O, N and S;
• D represents bond, or —C1-6 alkyl;
• E represents substituted aryl or substituted or unsubstituted heteroaryl;
• wherein heteroaryl is selected from mono- or bicyclic heterocyclic aromatic containing 1-3 hetero atoms selected from nitrogen, oxygen and sulphur;
• wherein aryl or heteroaryl is substituted by one or more substituents selected from C1-6 alkyl, C2-6 alkenyl, halogen, C1-6 alkoxy, cyano, hydroxy, nitro, amino, —N(CH3)2, —NHCOC1-6 alkyl, —OCF3, —CF3, —COOC1-6 alkyl, —OCHCF2, —SCF3, —CONR5R6, —SO2N(CH3)2, —SO2CH3 or —SCH3 groups, or unsubstituted or substituted fused cycloalkyl or heterocyclic rings, wherein fused cycloalkyl or heterocyclic rings optionally are substituted by carbonyl groups;
• wherein R5 and R6 each independently represent H, C1-6 alkyl or C1-4 alkylaryl;
• R18 represents halo, cyano, nitro, —OR16, —SR16, —COR16, —NR17COR16, —CONR16R17, optionally substituted phenoxy or —C1-6alkyl optionally substituted by —OR16;
• wherein:
• R16 represents H, —C1-6 alkyl or —C1-4 alkylaryl;
• R17 represents H or —C1-6 alkyl;
• m and n each independently represents 0 or an integer 1, 2 or 3;
• or
• a pharmaceutically acceptable salt thereof.

A method for treating idiopathic pulmonary fibrosis, which comprises administering to a human subject in need thereof an effective amount of a compound of formula (Id):

• wherein:
• R20 represents a substituted or unsubstituted aryl or heteroaryl group selected from phenyl, benzofuraryl and pyrimidinyl;
• and
• represents a substituted aryl or a substituted or unsubstituted heteroaryl group comprising at least one nitrogen atom;
• wherein heteroaryl is selected from mono- or bicyclic heterocyclic aromatic containing 1-3 hetero atoms selected from nitrogen, oxygen and sulphur;
• wherein aryl or heteroaryl is substituted by one or more substituents selected from C1-6 alkyl, C2-6 alkenyl, halogen, C1-6 alkoxy, cyano, hydroxy, nitro, amino, —N(CH3)2, —NHCOC1-6 alkyl, —OCF3, —CF3, —COOC1-6 alkyl, —OCHCF2, —SCF3, —CONR5R6, —SO2N(CH3)2, —SO2CH3 or —SCH3 groups, or unsubstituted or substituted fused cycloalkyl or heterocyclic rings, wherein fused cycloalkyl or heterocyclic rings optionally are substituted by carbonyl groups;
• wherein R5 and R6 each independently represent H, C1-6 alkyl or C1-4 alkylaryl;
• or
• a pharmaceutically acceptable salt thereof.