Design, Synthesis, and Pharmacological Evaluation of Highly Potent and Selective Dipeptidyl Peptidase-4 Inhibitors

doi:10.1002/ardp.201500082

	Design, Synthesis, and Pharmacological Evaluation of Highly Potent and Selective Dipeptidyl Peptidase-4 Inhibitors
	Jiang, Tao; Zhou, Yuren; Zhu, Jianming; Chen, Zhuxi; Sun, Peng; Zhang, Qiang; Wang, Zhen; Shao, Qiang; Jiang, Xiangrui; Li, Bo
刊名	ARCHIV DER PHARMAZIE
	2015-06
卷号	348 期号:6 页码:399-407
关键词	beta-Homophenylalanine DPP-4 Drug design Inhibitors P2-binding moiety
ISSN号	0365-6233
DOI	10.1002/ardp.201500082
文献子类	Article
英文摘要	The optimization of a series of fused -homophenylalanine inhibitors of dipeptidyl peptidase-4 (DPP-4) is described. Modification on the P2-binding moiety of 6 (IC50=10nM) led to the discovery of -homophenylalanine derivatives containing pyrrolidin-2-ylmethyl amides. The introduction of a sulfamine in the meta position of the phenyl ring improved the potency against DPP-4 (6-12-fold increase). Compound 14k showed DPP-4 inhibitory activity with an IC50 value of 0.87nM. Meanwhile, in vivo experiments exhibited that 14h had an efficiency comparable to sitagliptin at the dose of 10mg/kg.
资助项目	National Natural Science Foundation of China[21373258]
WOS关键词	IV INHIBITOR ; DISCOVERY
WOS研究方向	Pharmacology & Pharmacy ; Chemistry
语种	英语
出版者	WILEY-V C H VERLAG GMBH
WOS记录号	WOS:000355625200003
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/276511]
专题	药物化学研究室药物发现与设计中心药理学第三研究室
通讯作者	Jiang, Xiangrui
作者单位	Chinese Acad Sci, Shanghai Inst Mat Med, Key Lab Receptor Res, Drug Discovery & Design Ctr, Shanghai 201203, Peoples R China
推荐引用方式 GB/T 7714	Jiang, Tao,Zhou, Yuren,Zhu, Jianming,et al. Design, Synthesis, and Pharmacological Evaluation of Highly Potent and Selective Dipeptidyl Peptidase-4 Inhibitors[J]. ARCHIV DER PHARMAZIE,2015,348(6):399-407.
APA	Jiang, Tao.,Zhou, Yuren.,Zhu, Jianming.,Chen, Zhuxi.,Sun, Peng.,...&Shen, Jingshan.(2015).Design, Synthesis, and Pharmacological Evaluation of Highly Potent and Selective Dipeptidyl Peptidase-4 Inhibitors.ARCHIV DER PHARMAZIE,348(6),399-407.
MLA	Jiang, Tao,et al."Design, Synthesis, and Pharmacological Evaluation of Highly Potent and Selective Dipeptidyl Peptidase-4 Inhibitors".ARCHIV DER PHARMAZIE 348.6(2015):399-407.