Bioorganic and Medicinal Chemistry Letters p. 3059 - 3062 (2002)
Update date:2022-08-04
Topics:
Firooznia, Fariborz
Gude, Candido
Chan, Kenneth
Tan, Jenny
Fink, Cynthia A.
Savage, Paula
Beil, Michael E.
Bruseo, Charles W.
Trapani, Angelo J.
Jeng, Arco Y.
Directed screening of metalloprotease inhibitors identified CGS 30084 (1) as a potent inhibitor of endothelin-converting enzyme-1 (ECE-1) in vitro (IC50=77 nM). Herein we report the syntheses and biological activities of analogues containing modified biphenyl moieties, bearing heterocyclic proximal rings. Compound 20, the thioacetate ethyl ester prodrug derivative of compound 19a, was found to be an orally active and potent inhibitor of ECE-1 activity in rats.
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