Derivatives of 1,4-bis(3-hydroxycarbonyl-4-hydroxyl)styrylbenzene as PTP1B inhibitors with hypoglycemic activity.
Disalicylic acid derivatives with stilbene and bis-styrylbenzene skeleton were synthesized as PTP1B inhibitors. The most potent in this series exhibited a submicromolar IC(50) value. One of the compounds 7b was tested in an animal model for its efficacy as an anti-diabetic or an anti-obesity agent. In feeding compound 7b to diet-induced obese mice, no significant differences in weight gain and food consumption were observed between the drug-treated and the obese control mice. However, 7b significantly lowered the fasting glucose level and improved the glucose tolerance in the obesity-induced diabetic mice.
Shrestha
Suja
S
Department of Chemistry and Institute of Molecular Cell Biology, Inha University, Yonghyun-dong, Nam-ku, Incheon 402-751, Republic of Korea.
Bhattarai
Bharat Raj
BR
Kafle
Bhooshan
B
Lee
Keun-Hyeung
KH
Cho
Hyeongjin
H
D000818:Animals; D019440:Anti-Obesity Agents / Q000138:chemical synthesis / Q000494:pharmacology / Q000627:therapeutic use*; D001786:Blood Glucose / Q000032:analysis / Q000378:metabolism; D004195:Disease Models, Animal; D005215:Fasting; D005951:Glucose Tolerance Test; D006943:Hyperglycemia / Q000188:drug therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D009765:Obesity / Q000188:drug therapy*; D012459:Salicylates / Q000138:chemical synthesis / Q000494:pharmacology / Q000627:therapeutic use*; D013267:Stilbenes / Q000138:chemical synthesis / Q000494:pharmacology / Q000627:therapeutic use*; D013329:Structure-Activity Relationship; D013343:Styrenes / Q000138:chemical synthesis / Q000494:pharmacology / Q000627:therapeutic use*; D015430:Weight Gain / Q000187:drug effects*
D019440:Anti-Obesity Agents; D001786:Blood Glucose; D012459:Salicylates; D013267:Stilbenes; D013343:Styrenes; C014182:salicylsalicylic acid