Structure-based parallel medicinal chemistry approach to improve metabolic stability of benzopyran COX-2 inhibitors

被引：7
作者：
Xing, Li [1 ]
Hamper, Bruce C. [1 ]
Fletcher, Theresa R. [1 ]
Wendling, Jay M. [1 ]
Carter, Jeffery [1 ]
Gierse, James K. [1 ]
Liao, Subo [1 ]
机构：
[1] Pfizer Global Res & Dev, St Louis Labs, Chesterfield, MO 63017 USA
来源：
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2011年 / 21卷 / 03期
关键词：
Cyclooxygenase; COX-2; inhibitor; Benzopyran; Structure-based design; Parallel solid phase synthesis; Structure-activity relationship; Computer-assisted molecular modeling; Free energy perturbation; Metabolic stability; NONSTEROIDAL ANTIINFLAMMATORY DRUGS; PROSTAGLANDIN SYNTHESIS; SELECTIVE-INHIBITION; CYCLOOXYGENASE-2; INFLAMMATION; CELECOXIB;
D O I：
10.1016/j.bmcl.2010.12.023
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
Combination of the structure-based design and solid-phase parallel synthesis provided an integrated approach to rapidly develop the structure-activity relationship of benzopyran COX-2 inhibitors. Binding free energies predicted by free energy perturbation theory yielded good agreement with experimental results. New potent and selective lead compounds with improved metabolic properties were identified. (C) 2011 Elsevier Ltd. All rights reserved.
引用
收藏
页码：993 / 996
页数：4
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