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Bioorg Med Chem. 2015 Aug 1;23(15):4891-8. doi: 10.1016/j.bmc.2015.05.032. Epub 2015 Jun 9.

Discovery of novel, potent, selective and cellular active ADC type PTP1B inhibitors via fragment-docking-oriented de novel design.

Author information

1
School of Chemistry and Pharmaceutical Engineering, Qilu University of Technology, 3501 Daxue Road, Jinan 250353, China. Electronic address: ylduyjs@163.com.
2
School of Chemistry and Pharmaceutical Engineering, Qilu University of Technology, 3501 Daxue Road, Jinan 250353, China.
3
Brunswick Laboratories (China), 5 Xing Han Road, Suzhou 215021, China.
4
State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu Chong Zhi Road, Shanghai 201203, China.
5
Clinical Pharmacy Laboratory, Huashan Hospital, Fudan University, 12 Wu Lu Mu Qi M Road, Shanghai 200040, China. Electronic address: qyli1234@163.com.

Abstract

Fragment-docking-oriented de novel design for both the catalytic site and the C phosphotyrosine binding site led to the discovery of novel scaffold and chemical easy N-(2,5-diethoxy-phenyl)-methanesulfonamide based phosphotyrosine mimetics that when incorporated into ureas are high potent and selective inhibitors of protein tyrosine phosphatase 1B. Among them, compound 15 was shown to be the most potent PTP1B inhibitor with great selectivity over the highly homologous T-cell protein tyrosine phosphatase.

KEYWORDS:

Insulin signaling; N-(2,5-Diethoxy-phenyl)-methanesulfonamide; Protein tyrosine phosphatase 1B inhibitor; Type 2 diabetes mellitus

PMID:
26100442
DOI:
10.1016/j.bmc.2015.05.032
[Indexed for MEDLINE]

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