Sterling Winthrop Inc.

Sanofi Sa

Robert C Wahl

Bruce Edward Tomczuk

Ashis Kumar Saha

Ewell R Cook

Alan M Mathiowetz

Madhusudhan R Gowravaram

Jeffrey Johnson

Barry A Morgan

Thomas D Gordon

Jasbir Singh

James A Gainor

This disclosure relates to a novel class of hydroxamic and carboxylic acid based matrix metalloproteinase inhibitor derivatives. The disclosure further relates to pharmaceutical compositions containing such compounds and to the use of such compounds and compositions in the treatment of matrix metalloproteinase induced diseases.

Hydroxamic acid and carboxylic acid derivatives, process for their

Compounds having the structural formula ##STR1## wherein X is HONH or HO and especially wherein the carbon atom bearing CH.sub.2 R.sup.1 has the R-configuration, the carbon atom bearing CH.sub.2 R.sup.2 has the S-configuration, R.sup.1 is isopropyl, R.sup.2 is 3-indolyl, m is 2, n is 0, p is 2 and R.sup.3 and R.sup.4 taken alone are each methyl or R.sup.3 and R.sup.4 taken together with N are morpholino and pharmaceutically acceptable acid addition salts or solvates or acid addition salts-solvates thereof, which are matrix-metalloprotease inhibitors useful in treatment of disease in which matrix-metalloprotease promoted connective tissue remodelling is a causative factor, for example, rheumatoid arthritis and cancer, and a method of preparation and method of use thereof and methods of preparation of intermediates therefor are disclosed.

Succinamide derivative matrix-metalloprotease inhibitors

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Collegeville, PA, United States of America

Robert C Wahl