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ID: ALA3400139

Journal: Bioorg Med Chem Lett

Title: trans-(3S,4S)-Disubstituted pyrrolidines as inhibitors of the human aspartyl protease renin. Part I: prime site exploration using an amino linker.

Authors: Lorthiois E, Cumin F, Ehrhardt C, Kosaka T, Sellner H, Ostermann N, Francotte E, Wagner T, Maibaum J.

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.

CiteXplore: 25782742

DOI: 10.1016/j.bmcl.2015.02.039