- Discovery of 6-ethyl-2,4-diaminopyrimidine-based small molecule renin inhibitors.
Discovery of 6-ethyl-2,4-diaminopyrimidine-based small molecule renin inhibitors.
Bioorganic & medicinal chemistry letters (2007-05-08)
Daniel D Holsworth, Mehran Jalaie, Thomas Belliotti, Cuiman Cai, Wendy Collard, Suzie Ferreira, Noel A Powell, Michael Stier, Erli Zhang, Pat McConnell, Igor Mochalkin, Michael J Ryan, John Bryant, Tingsheng Li, Aparna Kasani, Rajendra Subedi, Samarendra N Maiti, Jeremy J Edmunds
PMID17482464
ABSTRACT
Novel 2,4-diaminopyrimidine-based small molecule renin inhibitors are disclosed. Through high throughput screening, parallel synthesis, X-ray crystallography, and structure based drug design, we have developed the first non-chiral, non-peptidic, small molecular template to possess moderate potency against renin. The designed compounds consist of a novel 6-ethyl-5-(1,2,3,4-tetrahydroquinolin-7-yl)pyrimidine-2,4-diamine ring system that exhibit moderate potency (IC(50): 91-650 nM) against renin while remaining 'Rule-of-five' compliant.
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