2-O-carboxymethylpyrogallol derivatives as PTP1B inhibitors with antihyperglycemic activity.
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.
Bhattarai
Bharat Raj
BR
Department of Chemistry and Institute of Molecular Cell Biology, Inha University, Incheon 402-751, Republic of Korea.
Shrestha
Suja
S
Ham
Seung Wook
SW
Kim
Kwang Rok
KR
Cheon
Hyae Gyeong
HG
Lee
Keun-Hyeung
KH
Cho
Hyeongjin
H
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002463:Cell Membrane Permeability / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy; D004041:Dietary Fats; D005951:Glucose Tolerance Test; D006943:Hyperglycemia / Q000188:drug therapy*; D007004:Hypoglycemic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D007333:Insulin Resistance; D007700:Kinetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors; D013329:Structure-Activity Relationship
D001786:Blood Glucose; D004041:Dietary Fats; D007004:Hypoglycemic Agents; D017027:Protein Tyrosine Phosphatases