Novel benzamido derivatives as PTP1B inhibitors with anti-hyperglycemic and lipid-lowering efficacy.
10.1016/j.apsb.2018.05.001
- Author:
Yanbo TANG
1
;
Xiaolin ZHANG
2
;
Zheng CHEN
1
;
Wenwen YIN
1
;
Guanglei NAN
1
;
Jinying TIAN
2
;
Fei YE
2
;
Zhiyan XIAO
1
Author Information
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.
- Publication Type:Journal Article
- Keywords:
Anti-hyperglycemic;
Benzamido derivatives;
Lipid-lowering;
PTP1B inhibitors;
Structureactivity relation-ship
- From:
Acta Pharmaceutica Sinica B
2018;8(6):919-932
- CountryChina
- Language:English
-
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 IC 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 on high-fat diet (HFD)-induced insulin-resistant (IR) obese mice indicated that could modulate glucose metabolism and ameliorate dyslipidemia simultaneously.
