Discovery of novel pyridyl carboxamides as potent CCR5 antagonists and optimization of their pharmacokinetic profile in rats.
Basic Information
ID: ALA1914281
Journal: Bioorg Med Chem Lett
Title: Discovery of novel pyridyl carboxamides as potent CCR5 antagonists and optimization of their pharmacokinetic profile in rats.
Authors: Duan M, Kazmierski WM, Chong PY, Deanda F, Edelstein M, Ferris R, Peckham J, Wheelan P, Xiong Z, Zhang H, Nishizawa R, Takaoka Y.
Abstract: A novel series of pyridyl carboxamide-based CCR5 inhibitors was designed, synthesized, and demonstrated to be highly potent against HIV-1 infection in both HOS and PBL assays. Attempts to evaluate this series of compounds in a rat PK model revealed its instability in rat plasma. A hypothesis for this liability was proposed, and strategies to overcome this issue were pursued, leading to discovery of highly potent 40 and 41, which featured dramatically improved rat PK profiles.
CiteXplore: 21920742
DOI: 10.1016/j.bmcl.2011.08.080
Patent ID: ┄