Design, Synthesis, and Biological Evaluation of (2R,αS)-3,4-Dihydro-2-[3-(1,1,2,2-tetrafluoroethoxy)phenyl]-5-[3-(trifluoromethoxy)-phenyl]-α-(trifluoromethyl)-1(2H)-quinolineethanol as Potent and Orally Active Cholesteryl Ester Transfer Protein Inhibitor

被引：39

作者：

Kuo, Gee-Hong ^{[1
]}

Rano, Thomas ^{[1
]}

Pelton, Patricia ^{[1
]}

Demarest, Keith T. ^{[1
]}

Gibbs, Alan C. ^{[1
]}

Murray, William V. ^{[1
]}

Damiano, Bruce P. ^{[1
]}

Connelly, Margery A. ^{[1
]}

机构：

[1] Johnson & Johnson Pharmaceut Res & Dev LLC, Drug Discovery Div, Cranbury, NJ 08512 USA

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2009年 / 52卷 / 06期

关键词：

HIGH-DENSITY LIPOPROTEIN; TORCETRAPIB; DISEASE; TRIALS; ATHEROSCLEROSIS; DYSLIPIDEMIA; THERAPIES; HDL;

D O I：

10.1021/jm801319d

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

With the goal of identifying a CETP inhibitor with high in vitro potency and optimal in vivo efficacy, a conformationally constrained molecule was designed based on the highly potent and flexible 13. The synthetic chemistry efforts led to the discovery of the potent and selective 12. In high-fat fed hamsters, human CETP transgenic mice, and cynomolgus monkeys, the in vivo efficacy of 12 for raising HDL-C was demonstrated to be comparable to torcetrapib.

引用

页码：1768 / 1772

页数：5

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