Discovery of novel dual-action antidiabetic agents that inhibit glycogen phosphorylase and activate glucokinase

doi:10.1016/j.ejmech.2012.06.020

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	Discovery of novel dual-action antidiabetic agents that inhibit glycogen phosphorylase and activate glucokinase
	Zhang, Lei 1; Chen, Xiaojie 1; Liu, Jun 2; Zhu, Qingzhang 1; Leng, Ying1 ; Luo, Xiaomin1 ; Jiang, Hualiang1 ; Liu, Hong1
刊名	EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
	2012-12
卷号	58 页码:624-639
关键词	Glycogen phosphorylase inhibitors Glucokinase activators Type 2 diabetes Dual-target-directed Hybrid
ISSN号	0223-5234
DOI	10.1016/j.ejmech.2012.06.020
文献子类	Article
英文摘要	Dual-target-directed agents simultaneously inhibiting glycogen phosphorylase (GP) and activating glucokinase (GK) could decelerate the inflow of glucose from glycogenolysis and accelerate the outflow of glucose in the liver, therefore allow for a better control over hyperglycaemia in a synergetic manner. A series of hybrid compounds were designed by structure-assisted and ligand-based strategies. In vitro bioassays found two novel compounds (1j, 6g) worthy of further optimization on balance of dual action to GP and GK. In addition, for single-target activity, two compounds exhibited more potent GP inhibitory activity and four compounds showed better GK activation than their corresponding references. (C) 2012 Elsevier Masson SAS. All rights reserved.
资助项目	National Basic Research Program of China[2009CB940903] ; National Basic Research Program of China[2012CB518000] ; National Natural Science Foundation of China[20721003] ; National Natural Science Foundation of China[81025017] ; National S&T Major Projects[2012ZX09103-101-072] ; Silver Project[260644]
WOS关键词	PPAR-ALPHA/GAMMA-AGONISTS ; DESIGNING MULTIPLE LIGANDS ; HEPATIC GLUCOSE-PRODUCTION ; TYPE-2 DIABETES THERAPY ; DRUG DISCOVERY ; LIVER ; METABOLISM ; PARADIGM ; ACIDS ; DERIVATIVES
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:000312745100064
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/277854]
专题	药理学第一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药理学第二研究室药物化学研究室
通讯作者	Leng, Ying
作者单位	1.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China; 2.China Pharmaceut Univ, Jiangsu Ctr Drug Screening, Nanjing 210038, Jiangsu, Peoples R China
推荐引用方式 GB/T 7714	Zhang, Lei,Chen, Xiaojie,Liu, Jun,et al. Discovery of novel dual-action antidiabetic agents that inhibit glycogen phosphorylase and activate glucokinase[J]. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,2012,58:624-639.
APA	Zhang, Lei.,Chen, Xiaojie.,Liu, Jun.,Zhu, Qingzhang.,Leng, Ying.,...&Liu, Hong.(2012).Discovery of novel dual-action antidiabetic agents that inhibit glycogen phosphorylase and activate glucokinase.EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,58,624-639.
MLA	Zhang, Lei,et al."Discovery of novel dual-action antidiabetic agents that inhibit glycogen phosphorylase and activate glucokinase".EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY 58(2012):624-639.