Structure-based drug design of a novel family of chalcones as PPARα agonists:virtual screening,synthesis,and biological activities in vitro

作     者：Xiang-hua LI~(2,3),Han-jun ZOU~(2,3),An-hui WU~2,Yang-liang YE~2,Jian-hua SHEN~(2,4)~2 Drug Discovery and Design Center,State Key Laboratory of Drug Research,Shanghai Institute of Materia Medica,Chinese Academy ofSciences,Shanghai 201203,China 

作者机构：Drug Discovery and Design Center State Key Laboratory of Drug Research Shanghai Institute of Materia Medica Chinese Academy of Sciences Shanghai China 

出 版 物：《Acta Pharmacologica Sinica》 (中国药理学报(英文版))

年 卷 期：2007年第28卷第12期

页      面：2040-2052页

核心收录：

学科分类：1007[医学-药学(可授医学、理学学位)] 10[医学] 

基　　金：Project supported by grants from the National Natural Science Foundation of China(№ 30623008) the Dengshan Project from the Shanghai Science and Technology Commission(№ 064319015) 

主　　题：peroxisome proliferator-activated receptors drug design virtual screening 

摘      要：Aim:To design and synthesize a novel class of peroxisome proliferator-activatedreceptors (PPAR)α agonists,which is obtained by the combination of the classi-cal fibratehead group,a linker with appropriate length and a ***:Thirty seven compounds were designed and identified employing the virtualscreening *** compounds were then selected for synthesis and bioas-say according to the virtual screening results,structural similarity,and ***:Six new compounds (4b and 4d-h) were synthesized *** were found to be potent PPARα agonists,compound 4 h being themost prominent with a 50% effective concentration value of 0.06 μmol/***:This study provides a promising novel family of chalcones with a potentialhypolipidemic effect.