2-O-carboxymethylpyrogallol derivatives as PTP1B inhibitors with antihyperglycemic activity

Bharat Raj Bhattarai; Suja Shrestha; Seung Wook Ham; Kwang Rok Kim; Hyae Gyeong Cheon; Keun-Hyeung Lee; Hyeongjin Cho

doi:10.1016/j.bmcl.2007.08.019

2-O-carboxymethylpyrogallol derivatives as PTP1B inhibitors with antihyperglycemic activity

Bioorg Med Chem Lett. 2007 Oct 1;17(19):5357-60. doi: 10.1016/j.bmcl.2007.08.019. Epub 2007 Aug 15.

Authors

Bharat Raj Bhattarai¹, Suja Shrestha, Seung Wook Ham, Kwang Rok Kim, Hyae Gyeong Cheon, Keun-Hyeung Lee, Hyeongjin Cho

Affiliation

¹ Department of Chemistry and Institute of Molecular Cell Biology, Inha University, Incheon 402-751, Republic of Korea.

PMID: 17728130
DOI: 10.1016/j.bmcl.2007.08.019

Abstract

2-O-carboxymethylpyrogallol derivatives (4-17) were synthesized, with their in vitro inhibitory activities against PTP1B and in vivo antihyperglycemic effects examined. Compound 14, the most potent among the series, showed a K(i) value of 1.1 microM against PTP1B, 7-fold lower than that against TC-PTP. When compound 14 was fed to a high-fat diet-induced diabetic mouse model, significant improvements were observed in both the fasting glucose level and glucose tolerance.

Publication types

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

MeSH terms

Animals
Blood Glucose / metabolism
Cell Membrane Permeability / drug effects
Diabetes Mellitus, Type 2 / drug therapy
Dietary Fats
Glucose Tolerance Test
Hyperglycemia / drug therapy*
Hypoglycemic Agents / chemical synthesis*
Hypoglycemic Agents / pharmacology*
Insulin Resistance
Kinetics
Male
Mice
Mice, Inbred C57BL
Protein Tyrosine Phosphatases / antagonists & inhibitors
Structure-Activity Relationship

Substances

Blood Glucose
Dietary Fats
Hypoglycemic Agents
Protein Tyrosine Phosphatases