152699-63-3

Selective MMP-13 inhibitors are isophthalic acid derivatives of the formula wherein: R1, R2, and R3 independently are hydrogen, halo, hydroxy, C1-C6 alkyl, C1-C6 alkoxy, C2-C6 alkenyl, C2-C6 alkynyl, NO2, NR4R5, CN, or CF3; E is independently O or S; A and B independently are OR4 or NR4R5; each R4 and R5 independently are H, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, (CH2)n aryl, (CH2)n cycloalkyl, (CH2)n heteroaryl, or R4 and R5 when taken together with the nitrogen to which they are attached complete a 3- to 8-membered ring, optionally containing a heteroatom selected from O, S, or NH, and optionally substituted or unsubstituted; n is 0 to 6; or a pharmaceutically acceptable salt thereof. The compounds are useful for treating diseases in a mammal that are mediated by MMP enzymes.

Compounds of formula (I) and their pharmaceutically active salts are gastrin and CCK receptor ligands, where Ar is a monocyclic aromatic group, R 1 is halo, amino, nitro, cyano, sulphamoyl, sulphonyl, trifluoromethyl, C 1 to C 3 alkyl, C 1 to C 3 alkylamino, C 1 to C 3 dialkylamino, phenyl, substituted phenyl, C 1 to C. sub.3 alkoxy, hydroxy, esterified hydroxy, C 1 to C 3 hydroxyalkyl, C 1 to C 3 alkylcarboxyamino, carboxy, esterified carboxy and amidated carboxy, m is 0, 1, 2, 3, or 4, provided that m is not more than 2 unless R 1 is exclusively halo, x+y=0 or 1, R 2 and R 4 independently are II, or C 1 to C 3 alkyl, R 3 is H or C 1 to C 15 hydrocarbyl, where one or more hydrogen atoms of die hydrocarbyl group may be replaced by a halogen atom, and where up to two of the carbon atoms may be replaced by a nitrogen, oxygen or sulphur atom, provided that R 3 does not contain a--O--O--group, R 5 is H or C 1 to C 3 alkyl, U is a cyclic moiety, selected from the group consisting of aryl, aromatic heterocyclic, non-aromatic heterocyclic, and cycloalkyl groups, where the aryl or aromatic group contains up to 3 substituents selected from the group consisting of halo, amino, nitro, cyano, sulphamoyl, sulphonyl, trifluoromethyl, C. sub.1 to C 3 alkyl, C 1 to C 3 alkylamino, C 1 to C 3 dialkylamino, phenyl, C 1 to C 3 alkoxy, hydroxy, esterified hydroxy, C 1 to C 3 hydroxyalkyl, C 1 to C 3 alkylcarboxyamino, carboxy, esterified carboxy and amidated carboxy, Z is a group of the formula (IIa) or (IIb) where R. sup.6 is H or C 1 to C. sub.3 alkyl, X is--CO 2 H, esterified carboxy, amidated carboxy, tetrazolyl, hydroxy, cyano, amidino,--CH 2 OH,--SO 2 NHCOR 7,--SONHCOR 7,--COR 7,--NHSO 2 R 7,--CONHSO 2 R. sup.7,--NHCOR 7 or--SO 2 NHR 8, where R. sup. 7 is C 1 to C 6, alkyl, C 1 to C 6 aryl or substituted aryl, and R 8 is--OH,--CN, C 1 to C 6 alkyl, C 1 to C. sub.6 haloalkyl, aryl or substituted aryl, Y is H or a group selected from those recited above for X, and a is 0, 1, or 2. STR1

Compounds of formula (Ia), (Ib), or (Ic), wherein A represents a group having two fused rings, or a group of formula (Id), R 1 (m) represents up to 6 substituents, K represents--O--,--S--,--CH 2--,--N(R 2)--or--N(COR 2)--, in which R 2 is H or C 1 to C 3 alkyl, W is a carbonyl, sulfonyl or sulfinyl group, provided that at least one of W and X contains carbonyl, Y and Z are as given in the description, and their pharmaceutically acceptable salts are ligands at CCK and/or gastrin receptors. STR1

The compounds of the formula I STR1 and their pharmaceutical acceptable salts, which are defined herein, are ligands for cholecystokinin and/or gastrin receptors.