Design and synthesis of new potent PTP1B inhibitors with the skeleton of 2-substituted imino-3-substituted-5-heteroarylidene-1,3-thiazolidine-4-one: Part I

doi:10.1016/j.ejmech.2016.05.060

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	Design and synthesis of new potent PTP1B inhibitors with the skeleton of 2-substituted imino-3-substituted-5-heteroarylidene-1,3-thiazolidine-4-one: Part I
	Meng, Ge 1; Zheng, Meilin 1; Wang, Mei 1; Tong, Jing 1; Ge, Weijuan 1; Zhang, Jiehe 1; Zheng, Aqun 2; Li, Jingya3 ; Gao, Lixin 3; Li, Jia3
刊名	EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
	2016-10-21
卷号	122 页码:756-769
关键词	1,3-Thiazolidine-4-one PTP1B Pyrrole Pyridine Dock SAR
ISSN号	0223-5234
DOI	10.1016/j.ejmech.2016.05.060
文献子类	Article
英文摘要	A new series of 2-substituted imino-3-substituted-5- heteroarylidene-1,3-thiazolidine 4 ones as the potent bidentate PTP1B inhibitors were designed and synthesized in this paper. All of the new compounds were characterized and identified by spectra analysis. The biological screening test against PTP1B showed that some of these compounds have the positive inhibitory activity against PTP1B. The activity of the compounds with 5-substituted pyrrole on 5-postion of 1,3-thiazolidine-4-one are more potent than that of those compounds with 5-substituted pyridine group. Compound 14b, 14h and 14i showed IC50 values of 8.66 mu M, 6.83 mu M and 6.09 mu M against PTP1B, respectively. Docking analysis of these active compounds with PTP1B showed the possible interaction modes of these biheterocyclic compounds with the active sites of PTP1B. The inhibition tests against oncogenetic CDC25B were also conducted on this set of compounds to evaluate the selectivity and possible anti-neoplastic activity. Compound 14b also showed the lowest IC50 of 1.66 mu M against CDC25B among all the possible inhibitors, including 14g, 14h, 14i and 15c. Some pharmacological parameters including VolSurf, steric and electric descriptors of all the compounds were calculated to give some hints about the relative relationship with the biological activity. The result of this study might give some light on designing the possible anti-cancer drugs targeting at phosphatases. The most active compound 14i might be used as the lead compound for further structure modification of the new low molecular weight PTP1B inhibitors with the N-containing heterocyclic skeleton. (C) 2016 Published by Elsevier Masson SAS.
资助项目	Shaanxi Province Science and Technology Research and Development Program of China, International Cooperation[2013KW31-04]
WOS关键词	TYROSINE-PHOSPHATASE 1B ; CDC25B PHOSPHATASE ; PTP-1B INHIBITORS ; SUBSTRATE-SPECIFICITY ; SELECTIVE INHIBITOR ; STRUCTURAL BASIS ; TRANSGENIC MICE ; SMALL-MOLECULE ; DISCOVERY ; OVEREXPRESSION
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:000383003900063
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/275851]
专题	国家新药筛选中心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物安全性评价中心
通讯作者	Meng, Ge; Li, Jia
作者单位	1.Xi An Jiao Tong Univ, Hlth Sci Ctr, Sch Pharm, 76 Yanta West Rd, Xian 710061, Shaanxi, Peoples R China; 2.Xi An Jiao Tong Univ, Sch Sci, 28 Xianning West Rd, Xian 710049, Shaanxi, Peoples R China; 3.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China
推荐引用方式 GB/T 7714	Meng, Ge,Zheng, Meilin,Wang, Mei,et al. Design and synthesis of new potent PTP1B inhibitors with the skeleton of 2-substituted imino-3-substituted-5-heteroarylidene-1,3-thiazolidine-4-one: Part I[J]. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,2016,122:756-769.
APA	Meng, Ge.,Zheng, Meilin.,Wang, Mei.,Tong, Jing.,Ge, Weijuan.,...&Li, Jia.(2016).Design and synthesis of new potent PTP1B inhibitors with the skeleton of 2-substituted imino-3-substituted-5-heteroarylidene-1,3-thiazolidine-4-one: Part I.EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,122,756-769.
MLA	Meng, Ge,et al."Design and synthesis of new potent PTP1B inhibitors with the skeleton of 2-substituted imino-3-substituted-5-heteroarylidene-1,3-thiazolidine-4-one: Part I".EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY 122(2016):756-769.