Synthesis of 5-Phenyl-1,3,4-thiadiazole Derivatives and Their Biochemical Evaluation against Src Homology 2 Domain-Containing Protein Tyrosine Phosphatase 1 (SHP1)

被引：5

作者：

Yu, Lijie ^{[1
]}

Feng, Bo ^{[2
,3
,4
]}

Wang, Zhijia ^{[1
]}

Gao, Lixin ^{[1
,2
]}

Zhang, Chun ^{[1
,5
]}

Rajendran, Satheeshkumar ^{[1
]}

Li, Jia ^{[2
]}

Zhou, Yubo ^{[2
,3
,4
]}

Wang, Wenlong ^{[1
]}

机构：

[1] Jiangnan Univ, Sch Pharmaceut Sci, Wuxi 214122, Jiangsu, Peoples R China

[2] Chinese Acad Sci, Natl Ctr Drug Screening, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China

[3] Chinese Acad Sci, Zhongshan Inst Drug Discovery, Inst Drug Discovery, Zhongshan 528400, Guangdong, Peoples R China

[4] Chinese Acad Sci, Zhongshan Inst Drug Discovery, Inst Dev, Zhongshan 528400, Guangdong, Peoples R China

[5] Nanjing Univ, Sch Chem & Chem Engn, Nanjing 210023, Peoples R China

来源：

CHINESE JOURNAL OF ORGANIC CHEMISTRY | 2021年 / 41卷 / 08期

基金：

中国国家自然科学基金;

关键词：

5-phenyl-1,3,4-thiadiazole derivatives; Src homology 2 domain-containing protein tyrosine phosphatase 1 (SHP1); inhibitors; structure-activity relationships; BIOLOGICAL EVALUATION; INHIBITORS; SPECIFICITY; SUBSTRATE; PTP1B;

D O I：

10.6023/cjoc202104041

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

The Src homology 2 domain-containing protein tyrosine phosphatase 1 (SHP1) is a convergent node for oncogenic cell-signaling cascades. Consequently, SHP1 represents a potential target for drug development in cancer treatment. Meanwhile only countable SHP1 inhibitors have been reported. A new type of SHP1 inhibitors with 5-phenyl-1,3,4-thiadiazole scaffold was developed. The representative compound 5b exhibited SHP1 inhibitory activity with IC50 of (1.33 +/- 0.16) mu mol/L, exhibited about 2-fold selectivity for SHP1 over SHP2, and had no detectable activity against PTP1B and TCPTP, and offered a novel scaffold to develop new SHP1 inhibitors.

引用

页码：3097 / 3105

页数：9

共 37 条

[11] Synthesis, antioxidant and antiproliferative activities of 1,3,4-thiadiazoles derived from phenolic acids
Jakovljevic, Katarina
Matic, Ivana Z.
Stanojkovic, Tatjana
Krivokuca, Ana
Markovic, Violeta
Joksovic, Milan D.
Mihailovic, Nevena
Niciforovic, Marija
Joksovic, Ljubinka
[J]. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2017, 27 (16) : 3709 - 3715
[12] Krishnan N, 2014, NAT CHEM BIOL, V10, P558, DOI [10.1038/NCHEMBIO.1528, 10.1038/nchembio.1528]
[13] Novel SHP-1 Inhibitors Tyrosine Phosphatase Inhibitor-1 and Analogs with Preclinical Anti-Tumor Activities as Tolerated Oral Agents
Kundu, Suman
Fan, Keke
Cao, Mingli
Lindner, Daniel J.
Zhao, Zhizhaung Joe
Borden, Ernest
Yi, Taolin
[J]. JOURNAL OF IMMUNOLOGY, 2010, 184 (11): : 6529 - 6536
[14] Inhibition protein tyrosine phosphatases by an oxovanadium glutamate complex, Na2[VO(Glu)2(CH3OH)](Glu = glutamate)
Lu, Liping
Wang, Sulian
Zhu, Miaoli
Liu, Zhiwei
Guo, Maolin
Xing, Shu
Fu, Xueqi
[J]. BIOMETALS, 2010, 23 (06) : 1139 - 1147
[15] A specific mechanism of nonspecific inhibition
McGovern, SL
Helfand, BT
Feng, B
Shoichet, BK
[J]. JOURNAL OF MEDICINAL CHEMISTRY, 2003, 46 (20) : 4265 - 4272
[16] Mfe C, 2019, J MOL STRUCT, V1179, P11
[17] AutoDock4 and AutoDockTools4: Automated Docking with Selective Receptor Flexibility
Morris, Garrett M.
Huey, Ruth
Lindstrom, William
Sanner, Michel F.
Belew, Richard K.
Goodsell, David S.
Olson, Arthur J.
[J]. JOURNAL OF COMPUTATIONAL CHEMISTRY, 2009, 30 (16) : 2785 - 2791
[18] Robb MA, 2016, Gaussian 09, Revision E.01
[19] 5-Hydroxy-2-Methyl-1,4-Naphthoquinone, a Vitamin K3 Analogue, Suppresses STAT3 Activation Pathway through Induction of Protein Tyrosine Phosphatase, SHP-1: Potential Role in Chemosensitization
Sandur, Santosh K.
Pandey, Manoj K.
Sung, Bokyung
Aggarwal, Bharat B.
[J]. MOLECULAR CANCER RESEARCH, 2010, 8 (01) : 107 - 118
[20] Synthesis and biological evaluation of heterocyclic bis-aryl amides as novel Src homology 2 domain containing protein tyrosine phosphatase-2 (SHP2) inhibitors
Satheeshkumar, Rajendran
Zhu, Rui
Feng, Bo
Huang, Chao
Gao, Ya
Gao, Li-Xin
Shen, Chao
Hou, Ting-Jun
Xu, Lei
Li, Jia
Zhu, Yun-Long
Zhou, Yu-Bo
Wang, Wen-Long
[J]. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2020, 30 (11)

← 1 2 3 4 →