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Bioorg Med Chem Lett. 2014 Apr 15;24(8):1889-94. doi: 10.1016/j.bmcl.2014.03.015. Epub 2014 Mar 15.

Synthesis and biological evaluation of novel bis-aromatic amides as novel PTP1B inhibitors.

Author information

1
School of Pharmaceutical Science, Jiangnan University, Wuxi 214122, China; State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China. Electronic address: wwenlong2011@163.com.
2
School of Pharmaceutical Science, Jiangnan University, Wuxi 214122, China.
3
State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
4
State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China. Electronic address: jli@mail.shcnc.ac.cn.
5
School of Pharmaceutical Science, Jiangnan University, Wuxi 214122, China; Jiangsu Alpha Biopharmaceuticals, Inc., Wuxi 214122, China. Electronic address: fengbainian@jiangnan.edu.cn.

Abstract

A series of bis-aromatic amides was designed, synthesized, and evaluated as a new class of inhibitors with IC50 values in the micromolar range against protein tyrosine phosphatase 1B (PTP1B). Among them, compound 15 displayed an IC50 value of 2.34±0.08 μM with 5-fold preference over TCPTP. More importantly, the treatment of CHO/HIR cells with compound 15 resulted in increased phosphorylation of insulin receptor (IR), which suggested extensive cellular activity of compound 15. These results provided novel lead compounds for the design of inhibitors of PTP1B as well as other PTPs.

KEYWORDS:

Bis-aromatic amides; Cellular activity; PTP1B inhibitors; Selectivity; Structure–activity relationships (SARs)

PMID:
24684845
DOI:
10.1016/j.bmcl.2014.03.015
[Indexed for MEDLINE]

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