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

Chin. J. Org. Chem. ›› 2019, Vol. 39 ›› Issue (9): 2599-2608.DOI: 10.6023/cjoc201901013 Previous Articles Next Articles

ARTICLE

含咔唑/苯并咪唑环的2,5-二取代-1,3,4-噻二唑酰胺衍生物的合成及对PTP1B/TCPTP抑制活性的评价

李英俊^a, 赵月^a, 靳焜^b, 高立信^c, 盛丽^c, 刘雪洁^a, 杨鸿境^a, 林乐弟^a, 李佳^c

a 辽宁师范大学化学化工学院大连 116029;
b 大连理工大学精细化工国家重点实验室大连 116012;
c 中国科学院上海药物研究所国家新药筛选中心药物研究国家重点实验室上海 201203

收稿日期:2019-01-10 修回日期:2019-04-12 发布日期:2019-04-16
通讯作者: 李英俊, 李佳 E-mail:chemlab.lnnu@163.com;jli@simm.ac.cn
基金资助:
辽宁省自然科学基金（No.20102126）资助项目.

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

Li Yingjun^a, Zhao Yue^a, Jin Kun^b, Gao Lixin^c, Sheng Li^c, Liu Xuejie^a, Yang Hongjing^a, Lin Ledi^a, Li Jia^c

a College of Chemistry and Chemical Engineering, Liaoning Normal University, Dalian 116029;
b State Key Laboratory of Fine Chemicals, Dalian University of Technology, Dalian 116012;
c National Center for Drug Screening, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203

Received:2019-01-10 Revised:2019-04-12 Published:2019-04-16
Contact: 10.6023/cjoc201901013 E-mail:chemlab.lnnu@163.com;jli@simm.ac.cn
Supported by:
Project supported by the Natural Science Foundation of Liaoning Province (No. 20102126).

1. Synthesis and PTP1B/TCPTP Inhibitory Activity Evaluation of Novel 2,5-Disubstituted-1,3,4-thiadiazolamide Derivatives Containing Carbazole/Benzimidazole Moity.PDF(6897KB)

Abstract

A series of novel 2,5-disubstituted-1,3,4-thiadiazolamide derivatives containing carbazole/benzimidazole moity were synthesized. Their structures were characterized by IR, ¹H NMR, ¹³C 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) μg/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 π-π interactions.

Key words: 1,3,4-thiadiazolamide, carbazole, benzimidazole, synthesis, PTP1B inhibitor, molecular docking, density functional theory (DFT) study

Cite this article

Li Yingjun, Zhao Yue, Jin Kun, Gao Lixin, Sheng Li, Liu Xuejie, Yang Hongjing, Lin Ledi, Li Jia. Synthesis and PTP1B/TCPTP Inhibitory Activity Evaluation of Novel 2,5-Disubstituted-1,3,4-thiadiazolamide Derivatives Containing Carbazole/Benzimidazole Moity[J]. Chin. J. Org. Chem., 2019, 39(9): 2599-2608.

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含咔唑/苯并咪唑环的2,5-二取代-1,3,4-噻二唑酰胺衍生物的合成及对PTP1B/TCPTP抑制活性的评价

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

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