Trans-(3S, 4S)-Disubstituted pyrrolidines as inhibitors of the human aspartyl protease renin. Part I: Prime site exploration using an amino linker. Issue 8 (15th April 2015)

• Record Type: Journal Article
• Authors: Lorthiois, Edwige; Cumin, Frederic; Ehrhardt, Claus; Kosaka, Takatoshi; Sellner, Holger; Ostermann, Nils; Francotte, Eric; Wagner, Trixie; Maibaum, Jürgen
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 25:Issue 8(2015)
• Page Start: 1782
• Page End: 1786
• Publication Date: 2015-04-15
• Subjects: Hypertension -- Direct renin inhibitor -- Structure guided drug design -- Pyrrolidine; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2015.02.039
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Abstract: Recently, we reported on the discovery of (3 S, 4 S )-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 (3 S )-amino functional group. In particular, analogs bearing the corresponding sulfonamide spacer (50, 51 and54a ) demonstrated a pronounced increase in in vitro potency compared to compound2 .