Dicarboxylic acid dipeptide neutral endopeptidase inhibitors

…, RD Ghai, R deJesus, C Diefenbacher…

Index: Ksander, Gary M.; Ghai, Raj D.; deJesus, Reynalda; Diefenbacher, Clive G.; Yuan, Andrew; et al. Journal of Medicinal Chemistry, 1995 ,  vol. 38,  # 10  p. 1689 - 1700

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Citation Number: 37

Abstract

The synthesis of three series of dicarboxylic acid dipeptide neutral endopeptidase 24.11 (NEP) inhibitors is described. In particular, the amino butyramide 21a exhibited potent NEP inhibitory activity (IC50= 5.0 nM) in vitro and in vivo. Blood levels of 21s were determined using an ex vivo method by measuring plasma inhibitory activity in conscious rats, mongrel dogs, and cynomolgus monkeys. Free drug concentrations were 10-1500 times greater ...