期刊
ACS MEDICINAL CHEMISTRY LETTERS
卷 5, 期 1, 页码 78-83出版社
AMER CHEMICAL SOC
DOI: 10.1021/ml4003953
关键词
Platelet-derived growth factor; fluoro-piperidine; fluorine; Pgp
The in silico construction of a PDGFR beta kinase homology model and ensuing medicinal chemistry guided by molecular modeling, led to the identification of potent, small molecule inhibitors of PDGFR Subsequent exploration of structure-activity relationships (SAR) led to the incorporation of a constrained secondary amine to enhance selectivity. Further refinements led to the integration of a fluorine substituted piperidine, which resulted M significant reduction of P-glycoprotein (Pgp) mediated efflux and improved bioavailability. Compound 28 displayed oral exposure in rodents and had a pronounced effect in a pharmacokinetic-pharmacodynamic (PKPD) assay.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据