Merck + Co., Inc.

Wilson B Knight

William K Hagmann

Richard A Mumford

John L Humes

William A Hanlon

Malcolm MacCoss

Shrenik K Shah

Paul E Finke

Alan L Maycock

N-substituted azetidinones are a class of inhibitors of human leukocytes elastase which are known to be useful in the treatment of a wide variety of antiinflammatory and antidegenerative diseases. In inhibiting elastase, the therapeutic agents are shown to form a characteristic stable complex with the enzyme. In the assay disclosed herein, the inhibitor-enzyme complex is advantageously hydrolyzed and specific product(s) of the hydrolysis are measured. The assays are useful in a clinical setting, for determining appropriate dosage and assessing the effectiveness of treatment.

Assay for evaluating inhibition of polymorphonuclear leukocyte elastase

Disclosed are .beta.-lactams of formula I ##STR1## wherein X is a chromogenic or fluorogenic substituted aryl or heteroaryl, which are specific inhibitors of Human leukocyte elastase (HLE). Upon contact with HLE these compounds are cleaved to form a chromogenic or fluorogenic species which may be readily measured by the assay disclosed herein. The assay thus provides a means for direct measurement of the amount of active HLE in a body fluid or other sample.

.beta.-lactams useful in determining the amount of elastase in a

Assay for evaluating inhibition of PMN elastase by N-substituted

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Watchung, NJ, United States of America

Wilson B Knight