Author/Authors :
Daniel D. Holsworth، نويسنده , , Mehran Jalaie، نويسنده , , Thomas Belliotti، نويسنده , , Cuiman Cai، نويسنده , , Wendy Collard، نويسنده , , Suzie Ferreira، نويسنده , , Noel A. Powell، نويسنده , , Michael Stier، نويسنده , , Erli Zhang، نويسنده , , Pat McConnell، نويسنده , , Igor Mochalkin، نويسنده , , MICHAEL J. RYAN، نويسنده , , john bryant، نويسنده , , Tingsheng Li، نويسنده , , Aparna Kasani، نويسنده , , Rajendra Subedi، نويسنده , , Samarendra N. Maiti، نويسنده , , Jeremy J. Edmunds، نويسنده ,
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 (IC50: 91–650 nM) against renin while remaining ‘Rule-of-five’ compliant.
Keywords :
renin inhibitor , hypertension , 2 , Structure based drug design , renin–angiotensin system , ras , Scaffold hopping , Conformational overlap , 4-Diaminopyrimidine
