[Design, synthesis and evaluation of malonic acid-based PTP1B inhibitors]

Xin Du; Shu-En Zhang; Jun-Zheng Liu; Fei-Lin Nie; Fei Ye; Jin-Ying Tian; Zhi-Yan Xiao

[Design, synthesis and evaluation of malonic acid-based PTP1B inhibitors]

Yao Xue Xue Bao. 2012 Mar;47(3):367-73.

[Article in Chinese]

Authors

Xin Du¹, Shu-En Zhang, Jun-Zheng Liu, Fei-Lin Nie, Fei Ye, Jin-Ying Tian, Zhi-Yan Xiao

Affiliation

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.

PMID: 22645761

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.

Publication types

English Abstract
Research Support, Non-U.S. Gov't

MeSH terms

Drug Design*
Enzyme Inhibitors / chemical synthesis*
Enzyme Inhibitors / chemistry
Enzyme Inhibitors / pharmacology
Humans
Inhibitory Concentration 50
Malonates / chemical synthesis*
Malonates / chemistry
Malonates / pharmacology
Molecular Structure
Protein Tyrosine Phosphatase, Non-Receptor Type 1 / antagonists & inhibitors*
Protein Tyrosine Phosphatase, Non-Receptor Type 1 / metabolism
Structure-Activity Relationship

Substances

Enzyme Inhibitors
Malonates
malonic acid
Protein Tyrosine Phosphatase, Non-Receptor Type 1