Lorthiois, Edwige, Cumin, Frederic, Ehrhardt, Claus, Kosaka, Takatoshi, Sellner, Holger, Ostermann, Nils, Wagner, Beatrix, Maibaum, Juergen Klaus and Francotte, Eric (2014) Trans-(3S,4S)-Disubstituted Pyrrolidines as Inhibitors of the Human Aspartyl Protease Renin. Part I: Prime Site exploration using an amino linker. Bioorganic and medicinal chemistry letters, 25 (8). pp. 1782-1786. ISSN 0960894X

Abstract

Recently, we reported on the discovery of (3S,4S)-disubstituted pyrrolidines (e.g. 2) as inhibitors of the human aspartyl protease renin. In our effort to further expand the scope of this novel class of direct renin inhibitors, a new sub-series was designed in which the prime site substituents are linked to the pyrrolidine core by a (3S)-amino functional group. In particular, analogs bearing the corresponding sulfonamide spacer (50, 51 and 54a) demonstrated a pronounced increase in in vitro potency compared to compound 2.

Item Type:	Article
Keywords:	Hypertension, direct renin inhibitor, structure guided drug design, pyrrolidine
Date Deposited:	13 Oct 2015 13:11
Last Modified:	04 Jul 2016 23:45
URI:	https://oak.novartis.com/id/eprint/24498