Novel benzamido derivatives as PTP1B inhibitors with anti-hyperglycemic and lipid-lowering efficacy

Yanbo Tang; Xiaolin Zhang; Zheng Chen; Wenwen Yin; Guanglei Nan; Jinying Tian; Fei Ye; Zhiyan Xiao

doi:10.1016/j.apsb.2018.05.001

Novel benzamido derivatives as PTP1B inhibitors with anti-hyperglycemic and lipid-lowering efficacy

Acta Pharm Sin B. 2018 Oct;8(6):919-932. doi: 10.1016/j.apsb.2018.05.001. Epub 2018 May 8.

Authors

Yanbo Tang¹, Xiaolin Zhang², Zheng Chen¹, Wenwen Yin¹, Guanglei Nan¹, Jinying Tian², Fei Ye², Zhiyan Xiao¹

Affiliations

¹ Beijing Key Laboratory of Active Substance Discovery and Druggability Evaluation, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
² Beijing Key Laboratory of New Drug Mechanisms and Pharmacological Evaluation Study, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.

Abstract

Based on a non-competitive and selective PTP1B inhibitor reported by us previously, thirty-nine benzamido derivatives were designed and synthesized as novel PTP1B inhibitors. Among them, twelve compounds exhibited IC₅₀ values at micromolar level against human recombinant PTP1B, and most of them exhibited significant selectivity to PTP1B over TC-PTP and CD45. Further evaluation of the most potent compound 27 on high-fat diet (HFD)-induced insulin-resistant (IR) obese mice indicated that 27 could modulate glucose metabolism and ameliorate dyslipidemia simultaneously.

Keywords: Anti-hyperglycemic; Benzamido derivatives; Lipid-lowering; PTP1B inhibitors; Structureactivity relation-ship.