| Literature DB >> 17574423 |
Noel A Powell1, Fred L Ciske, Cuiman Cai, Daniel D Holsworth, Ken Mennen, Chad A Van Huis, Mehran Jalaie, Jacqueline Day, Michelle Mastronardi, Pat McConnell, Igor Mochalkin, Erli Zhang, Michael J Ryan, John Bryant, Wendy Collard, Suzie Ferreira, Chungang Gu, Roxane Collins, Jeremy J Edmunds.
Abstract
We report the design and synthesis of a series of 6-(2,4-diaminopyrimidinyl)-1,4-benzoxazin-3-ones as orally bioavailable small molecule inhibitors of renin. Compounds with a 2-methyl-2-aryl substitution pattern exhibit potent renin inhibition and good permeability, solubility, and metabolic stability. Oral bioavailability was found to be dependent on metabolic clearance and cellular permeability, and was optimized through modulation of the sidechain that binds in the S3(sp) subsite.Entities:
Mesh：
Substances：
Year: 2007 PMID： 17574423 DOI： 10.1016/j.bmc.2007.05.069
Source DB: PubMed Journal: Bioorg Med Chem ISSN： 0968-0896 Impact factor: 3.641