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ID: ALA1135193

Journal: Bioorg Med Chem Lett

Title: N-[2-(Indan-1-yl)-3-mercapto-propionyl] amino acids as highly potent inhibitors of the three vasopeptidases (NEP, ACE, ECE): In vitro and In vivo activities.

Authors: Inguimbert N, Poras H, Teffo F, Beslot F, Selkti M, Tomas A, Scalbert E, Bennejean C, Renard P, Fournié-Zaluski MC, Roques BP.

Abstract: We have previously reported the design of a lead compound 1a for the joint inhibition of neprilysin (NEP, EC 3.4.24.11), angiotensin converting enzyme (ACE, EC 3.4.15.1) and endothelin converting enzyme (ECE-1, EC 3.4.24.71), three metallopeptidases which are implicated in the regulation of fluid homeostasis and vascular tone. We report here the synthesis and biological activities of analogues derived from this lead with inhibitory potencies in the nanomolar range for the three enzymes. Compounds 8b and 15c are the most potent triple inhibitors described to date.

CiteXplore: 12113828

DOI: 10.1016/s0960-894x(02)00248-2