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Trans-(3S,4S)-Disubstituted Pyrrolidines as Inhibitors of the Human Aspartyl Protease Renin. Part I: Prime Site exploration using an amino linker

Lorthiois, Edwige and Cumin, Frederic and Ehrhardt, Claus and Kosaka, Takatoshi and Sellner, Holger and Ostermann, Nils and Wagner, Beatrix and 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

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