Design and synthesis of a new class of malonyl-CoA decarboxylase inhibitors with anti-obesity and anti-diabetic activities.

Abstract

A new series of thiazole-substituted 1,1,1,3,3,3-hexafluoro-2-propanols were prepared and evaluated as malonyl-CoA decarboxylase (MCD) inhibitors. Key analogs caused dose-dependent decreases in food intake and body weight in obese mice. Acute treatment with these compounds also led to a drop in elevated blood glucose in a murine model of type II diabetes.

• Authors: Haifeng Tang, Yan Yan, Zhe Feng, Reynalda K de Jesus, Lihu Yang, Dorothy A Levorse, Karen A Owens, Taro E Akiyama, Raynald Bergeron, Gino A Castriota, Thomas W Doebber, Kenneth P Ellsworth, Michael E Lassman, Cai Li, Margaret S Wu, Bei B Zhang, Kevin T Chapman, Sander G Mills, Joel P Berger, Alexander Pasternak
• Journal: Bioorganic & medicinal chemistry letters (Bioorg Med Chem Lett) Vol. 20 Issue 20 Pg. 6088-92 (Oct 15 2010) ISSN: 1464-3405 [Electronic] England
• PMID: 20832306 (Publication Type: Journal Article)
• Copyright: Published by Elsevier Ltd.

Chemical References

• Anti-Obesity Agents
• Blood Glucose
• Hypoglycemic Agents
• Propanols
• Thiazoles
• hexafluoroisopropanol
• Carboxy-Lyases
• malonyl-CoA decarboxylase

Topics

• Animals
• Anti-Obesity Agents (chemical synthesis, chemistry, pharmacology, therapeutic use)
• Blood Glucose (drug effects)
• Body Weight (drug effects)
• Carboxy-Lyases (antagonists & inhibitors, metabolism)
• Diabetes Mellitus, Type 2 (drug therapy)
• Drug Design
• Eating (drug effects)
• Humans
• Hypoglycemic Agents (chemical synthesis, chemistry, pharmacology, therapeutic use)
• Mice
• Mice, Inbred C57BL
• Obesity (drug therapy)
• Propanols (chemical synthesis, chemistry, pharmacology, therapeutic use)
• Thiazoles (chemical synthesis, chemistry, pharmacology, therapeutic use)