Dual metalloprotease inhibitors: mercaptoacetyl-based fused heterocyclic dipeptide mimetics as inhibitors of angiotensin-converting enzyme and neutral …

…, MP Cimarusti, T Dejneka, WA Slusarchyk…

Index: Robl, Jeffrey A.; Sun, Chong-Qing; Stevenson, Jay; Ryono, Denis E.; Simpkins, Ligaya M.; Cimarusti, Maria P.; Dejneka, Tamara; Slusarchyk, William A.; Chao, Sam; Stratton, Leslie; Misra, Raj N.; Bednarz, Mark S.; Asaad, Magdi M.; Cheung, Hong Son; Abboa-Offei, Benoni E.; Smith, Patricia L.; Mathers, Parker D.; Fox, Maxine; Schaeffer, Thomas R.; Seymour, Andrea A.; Trippodo, Nick C. Journal of Medicinal Chemistry, 1997 , vol. 40, # 11 p. 1570 - 1577

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Citation Number: 196

Abstract

A series of 7, 6-and 7, 5-fused bicyclic thiazepinones and oxazepinones were generated and incorporated as conformationally restricted dipeptide surrogates in mercaptoacyl dipeptides. These compounds are potent inhibitors of angiotensin-converting enzyme (ACE) and neutral endopeptidase (NEP) both in vitro and in vivo. Compound 1a, a 7, 6-fused bicyclic thiazepinone, demonstrated excellent blood pressure lowering in a variety of ...