Design and optimization of a substituted amino propanamide series of renin inhibitors for the treatment of hypertension.
Basic Information
ID: ALA1156309
Journal: Bioorg Med Chem Lett
Title: Design and optimization of a substituted amino propanamide series of renin inhibitors for the treatment of hypertension.
Authors: Chen A, Bayly C, Bezençon O, Richard-Bildstein S, Dubé D, Dubé L, Gagné S, Gallant M, Gaudreault M, Grimm E, Houle R, Lacombe P, Laliberté S, Lévesque JF, Liu S, MacDonald D, Mackay B, Martin D, McKay D, Powell D, Remen L, Soisson S, Toulmond S.
Abstract: The discovery and SAR of a new series of substituted amino propanamide renin inhibitors are herein described. This work has led to the preparation of compounds with in vitro and in vivo profiles suitable for further development. Specifically, challenges pertaining to oral bioavailability, covalent binding and time-dependent CYP 3A4 inhibition were overcome thereby culminating in the identification of compound 50 as an optimized renin inhibitor with good efficacy in the hypertensive double-transgenic rat model.
CiteXplore: 20206513
DOI: 10.1016/j.bmcl.2010.02.036
Patent ID: ┄