Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
1361740 | Bioorganic & Medicinal Chemistry Letters | 2011 | 8 Pages |
Abstract
Structure-based design led to the discovery of a novel class of renin inhibitors in which an unprecedented phenyl ring filling the S1 site is attached to the phenyl ring filling the S3 pocket. Optimization for several parameters including potency in the presence of human plasma, selectivity against CYP3A4 inhibition and improved rat oral bioavailability led to the identification of 8d which demonstrated antihypertensive efficacy in a transgenic rat model of human hypertension.
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Physical Sciences and Engineering
Chemistry
Organic Chemistry
Authors
Jing Yuan, Robert D. Simpson, Wei Zhao, Colin M. Tice, Zhenrong Xu, Salvacion Cacatian, Lanqi Jia, Patrick T. Flaherty, Joan Guo, Alexey Ishchenko, Zhongren Wu, Brian M. McKeever, Boyd B. Scott, Yuri Bukhtiyarov, Jennifer Berbaum, Reshma Panemangalore,