Tryptophan-containing dipeptide derivatives as potent PPAR gamma antagonists: Design, synthesis, biological evaluation, and molecular modeling

doi:10.1016/j.ejmech.2008.01.032

	Tryptophan-containing dipeptide derivatives as potent PPAR gamma antagonists: Design, synthesis, biological evaluation, and molecular modeling
	Deng, Guanghui 2; Liu, Zhiguo 2; Ye, Fei 2; Luo, Xiaomin2 ; Zhu, Weiliang2 ; Shen, Xu1,2 ; Liu, Hong2 ; Jiang, Hualiang1,2
刊名	EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
	2008-12
卷号	43 期号:12 页码:2699-2716
关键词	Difficult sequence Dipeptide PPAR SAR Tryptophan
ISSN号	0223-5234
DOI	10.1016/j.ejmech.2008.01.032
文献子类	Article
英文摘要	The discovery of peroxisome proliferator-activated receptor gamma (PPAR gamma) antagonists (also termed "selective PPAR gamma modulators, SPPAR gamma M") is now of a great interest in the treatment of diabetes and obesity. The structure of compound la (G3335, Fig. 1), a novel class of PPAR gamma antagonist, is entirely different from that of other reported PPAR gamma antagonists. A series of 35 novel analogues (1b-1, 9a-d, 13a-t) were designed, synthesized and evaluated against the agonistic effects exerted by rosiglitazone. These results indicated that most functional groups of la were conserved, and six new compounds (1b, 1c, and 9a-d) exhibited strong PPAR gamma antagonistic activities (IC50 values of 5.2-25.8 mu M) against 10 mu M rosiglitazone in the promotion of the PPAR gamma-LBD-CBP (ligand-binding domain and cAMP-response-element binding protein) interaction as investigated by yeast two-hybrid technology based assay. Molecular modeling studies for compounds 1a-d, 1h, 9c-d, and 13a were also presented. (C) 2008 Elsevier Masson SAS. All rights reserved.
资助项目	National Natural Science Foundation of China[20372069] ; National Natural Science Foundation of China[29725203] ; National Natural Science Foundation of China[20472094] ; Key Technologies R&D Program from CAS[2006BAI011302] ; Key Technologies R&D Program from CAS[2005BA711A01] ; 863 Hi-Tech Program of China[2006AA020402] ; 863 Hi-Tech Program of China[2006AA020602]
WOS关键词	ACTIVATED-RECEPTOR-GAMMA ; ADIPOCYTE DIFFERENTIATION ; ANTIDIABETIC ACTIVITY ; INSULIN SENSITIZER ; GENE-EXPRESSION ; LIGAND-BINDING ; IN-VITRO ; MODULATOR ; AGONISTS ; OBESITY
WOS研究方向	Pharmacology & Pharmacy
语种	英语
出版者	ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
WOS记录号	WOS:000261984000008
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/279416]
专题	药物化学研究室中科院受体结构与功能重点实验室新药研究国家重点实验室
通讯作者	Liu, Hong
作者单位	1.E China Univ Sci & Technol, Sch Pharm, Shanghai 200237, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Biol Sci, Grad Sch, State Key Lab Drug Res,Shanghai Inst Mat Med,Drug, Shanghai 201203, Peoples R China;
推荐引用方式 GB/T 7714	Deng, Guanghui,Liu, Zhiguo,Ye, Fei,et al. Tryptophan-containing dipeptide derivatives as potent PPAR gamma antagonists: Design, synthesis, biological evaluation, and molecular modeling[J]. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,2008,43(12):2699-2716.
APA	Deng, Guanghui.,Liu, Zhiguo.,Ye, Fei.,Luo, Xiaomin.,Zhu, Weiliang.,...&Jiang, Hualiang.(2008).Tryptophan-containing dipeptide derivatives as potent PPAR gamma antagonists: Design, synthesis, biological evaluation, and molecular modeling.EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,43(12),2699-2716.
MLA	Deng, Guanghui,et al."Tryptophan-containing dipeptide derivatives as potent PPAR gamma antagonists: Design, synthesis, biological evaluation, and molecular modeling".EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY 43.12(2008):2699-2716.