Discovery of renin inhibitors containing a simple aspartate binding moiety that imparts reduced P450 inhibition. Issue 21 (1st November 2017)

• Record Type: Journal Article
• Authors: Lawhorn, Brian G.; Tran, Tritin; Hong, Victor S.; Morgan, Lisa A.; Le, BaoChau T.; Harpel, Mark R.; Jolivette, Larry; Diaz, Elsie; Schwartz, Benjamin; Gross, Jeffrey W.; Tomaszek, Thaddeus; Semus, Simon; Concha, Nestor; Smallwood, Angela; Holt, Dennis A.; Kallander, Lara S.
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 27:Issue 21(2017)
• Page Start: 4838
• Page End: 4843
• Publication Date: 2017-11-01
• Subjects: Renin inhibitors -- Cyp3A4 -- Biphenyl -- Hypertension -- X-ray crystallography; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2017.09.046
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Abstract: Discovery of potent renin inhibitors which contain a simplified alkylamino Asp-binding group and exhibit improved selectivity for renin over Cyp3A4 is described. Structure-function results in this series are rationalized based on analysis of selected compounds bound to renin, and the contribution of each molecular feature leading to the reduced P450 inhibition is quantified.