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Bioorg Med Chem Lett. 2012 Apr 15;22(8):2670-4. doi: 10.1016/j.bmcl.2012.03.014. Epub 2012 Mar 11.

Design and synthesis of potent, isoxazole-containing renin inhibitors.

Author information

1
Merck Frosst Centre for Therapeutic Research, Kirkland, Québec, Canada. pierre-andre_fournier@merck.com

Abstract

The design and optimization of a novel isoxazole S(1) linker for renin inhibitor is described herein. This effort culminated in the identification of compound 18, an orally bioavailable, sub-nanomolar renin inhibitor even in the presence of human plasma. When compound 18 was found to inhibit CYP3A4 in a time dependent manner, two strategies were pursued that successfully delivered equipotent compounds with minimal TDI potential.

PMID:
22450130
DOI:
10.1016/j.bmcl.2012.03.014
[Indexed for MEDLINE]

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