Synthesis and PTP1B/TCPTP Inhibitory Activity Evaluation of Novel 2,5-Disubstituted-1,3,4-thiadiazolamide Derivatives Containing Carbazole/Benzimidazole Moity

doi:10.6023/cjoc201901013

	Synthesis and PTP1B/TCPTP Inhibitory Activity Evaluation of Novel 2,5-Disubstituted-1,3,4-thiadiazolamide Derivatives Containing Carbazole/Benzimidazole Moity
	Li Yingjun 3; Zhao Yue 3; Jin Kun 1; Gao Lixin 2; Sheng Li 2; Liu Xuejie 3; Yang Hongjing 3; Lin Ledi 3; Li Jia 2
刊名	CHINESE JOURNAL OF ORGANIC CHEMISTRY
	2019-09-01
卷号	39 期号:9 页码:2599-2608
关键词	1,3,4-thiadiazolamide carbazole benzimidazole synthesis PTP1B inhibitor molecular docking density functional theory (DFT) study
ISSN号	0253-2786
DOI	10.6023/cjoc201901013
通讯作者	Li Yingjun(chemlab.lnnu@163.com) ; Li Jia(jli@simm.ac.cn)
英文摘要	A series of novel 2,5-disubstituted-1,3,4-thiadiazolamide derivatives containing carbazole/benzimidazole moity were synthesized. Their structures were characterized by IR, H-1 NMR, C-13 NMR spectra and elemental analysis. All synthesized target compounds were evaluated for the inhibitory activities against protein tyrosine phosphatase 1B (PTP1B) and T-cell protein tyrosine phosphatase (TCPTP). The structure-activity relationship was discussed. The results showed that most of compounds had good inhibitory activity against PTP1B over the highly homologous TCPTP, and 2-(9-carbazolylmethylene)-5-(3-chlorobenzoylamino)-1,3,4-thiadiazole (5c) displayed the highest inhibitory activity against PTP1B [IC50=(2.43 +/- 0.43) mu g/mL]. The inhibitory activities of 2-(9- carbazolylmethylene)-5-(4-methylbenzoylamino)-1,3,4-thiadiazole (5b) and 5c against PTP1B were higher than that of positive control oleanolic acid. Molecular docking and density functional theory (DFT) calculations of the target compound 5c were performed. The docking result showed that compound 5c and PTP1B enzyme formed a stable complex by hydrogen bonds, hydrophobic and pi-pi interactions.
资助项目	Natural Science Foundation of Liaoning Province[20102126]
WOS关键词	PROTEIN-TYROSINE PHOSPHATASES ; BENZIMIDAZOLE DERIVATIVES ; BIOLOGICAL EVALUATION ; PTP1B INHIBITORS ; DISCOVERY ; 1,3,4-THIADIAZOLES ; ANTIOXIDANT ; THIADIAZOLE ; SELECTIVITY ; POTENT
WOS研究方向	Chemistry
语种	英语
出版者	SCIENCE PRESS
WOS记录号	WOS:000489272700025
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/282619]
专题	中国科学院上海药物研究所
通讯作者	Li Yingjun; Li Jia
作者单位	1.Dalian Univ Technol, State Key Lab Fine Chem, Dalian 116012, Peoples R China 2.Chinese Acad Sci, Natl Ctr Drug Screening, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China 3.Liaoning Normal Univ, Coll Chem & Chem Engn, Dalian 116029, Peoples R China
推荐引用方式 GB/T 7714	Li Yingjun,Zhao Yue,Jin Kun,et al. Synthesis and PTP1B/TCPTP Inhibitory Activity Evaluation of Novel 2,5-Disubstituted-1,3,4-thiadiazolamide Derivatives Containing Carbazole/Benzimidazole Moity[J]. CHINESE JOURNAL OF ORGANIC CHEMISTRY,2019,39(9):2599-2608.
APA	Li Yingjun.,Zhao Yue.,Jin Kun.,Gao Lixin.,Sheng Li.,...&Li Jia.(2019).Synthesis and PTP1B/TCPTP Inhibitory Activity Evaluation of Novel 2,5-Disubstituted-1,3,4-thiadiazolamide Derivatives Containing Carbazole/Benzimidazole Moity.CHINESE JOURNAL OF ORGANIC CHEMISTRY,39(9),2599-2608.
MLA	Li Yingjun,et al."Synthesis and PTP1B/TCPTP Inhibitory Activity Evaluation of Novel 2,5-Disubstituted-1,3,4-thiadiazolamide Derivatives Containing Carbazole/Benzimidazole Moity".CHINESE JOURNAL OF ORGANIC CHEMISTRY 39.9(2019):2599-2608.