Salts of thiol sulfonamide inhibitors for matrix metalloproteinase 13 (MMP-13)

摘要

A matrix metalloprotease inhibitor compound corresponding to the formula (Ia), (IIa) or (IIIa) useful for the treatment of conditions associated with pathological matrix metalloprotease activities, such as rheumatoid arthritis, osteoarthritis, septic arthritis; corneal, epidermal or gastric ulceration; tumour metastasis, invasion or angiogenesis; periodontal disease; proteinuria; Alzheimers Disease; coronary thrombosis and bone disease. Wherein; R1 is a substituted 5- or 6-membered ring, having a length greater than that of a saturated four carbon chain, and shorter than that of a saturated eighteen carbon chain, and when rotated about an axis drawn through the SO2 -bonded position and the 4-position of a 6-membered ring or the SO2-bonded position and substituent-bonded 3- or position of a 5-membered ring defines a three-dimensional volume whose widest dimension has the width of about one phenyl ring to about three phenyl rings in a direction transverse to that axis to rotation; R2 is selected from the group consisting of hydrido, a C1-6alkyl group, C1-4alkylaryl comprising a single ring, C1-4alkylheteroaryl comprising a single ring, a C2-4alkyl group substituted by amino, mono-substituted amino or di-substituted amino, wherein the substituents on nitrogen are chosen from C1-6alkyl, aralkyl, C5-8cycloalkyl and C1-6alkanoyl, or wherein the two substituents and the nitrogen to which they are attached when taken together form a 5- to 8-membered heterocyclo or heterozaryl ring containing zero or one additional hetero atoms that are nitrogen, oxygen or sulphur; R4 is a hydroxycarbonyl, aminocarbonyl or C1-6alkyl group; W is oxygen or sulphur; and R9 is a C1-6alkyl group, a C1-6alkoxy group, or a single-ringed carbocyclic aryl or heteroaryl group, with the proviso that R2 is hydrido only when R1 is 4-(phenylazo)phenyl.