Design, synthesis and evaluation of malonic acid-based PTP1B inhibitors.
- Author:
Xin DU
1
;
Shu-En ZHANG
;
Jun-Zheng LIU
;
Fei-Lin NIE
;
Fei YE
;
Jin-Ying TIAN
;
Zhi-Yan XIAO
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.
- Publication Type:Journal Article
- MeSH:
Drug Design;
Enzyme Inhibitors;
chemical synthesis;
chemistry;
pharmacology;
Humans;
Inhibitory Concentration 50;
Malonates;
chemical synthesis;
chemistry;
pharmacology;
Molecular Structure;
Protein Tyrosine Phosphatase, Non-Receptor Type 1;
antagonists & inhibitors;
metabolism;
Structure-Activity Relationship
- From:
Acta Pharmaceutica Sinica
2012;47(3):367-373
- CountryChina
- Language:Chinese
-
Abstract:
Protein tyrosine phosphatase (PTP) 1B is a potential target for the treatment of diabetes and obesity. Phosphotyrosine (pTyr) is the substrate for PTP1B dephosphorylation. Malonic acid moiety was used herein as a mimic of the phosphate group in pTyr, and novel malonic acid derivatives 1-7 were designed, synthesized and evaluated as PTP1B inhibitors. Results from enzymatic assays indicated that compounds 3 and 4 exhibited potent inhibition against human recombinant PTP1B with IC50 values of 7.66 and 1.88 micromol x L(-1), respectively.
