Title of article :
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
Author/Authors :
Nicolas Inguimbert، نويسنده , , Hervé Poras، نويسنده , , Franck Teffo، نويسنده , , Françoise Beslot، نويسنده , , Mohamed Selkti، نويسنده , , Alain Tomas، نويسنده , , Elizabeth Scalbert، نويسنده , , Caroline Bennejean، نويسنده , , Pierre Renard، نويسنده , , Marie-Claude Fournie-Zaluski، نويسنده , , Bernard-Pierre Roques، نويسنده ,
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.
