SAR and optimization of thiazole analogs as potent stearoyl-CoA desaturase inhibitors

详细信息    查看全文

• 作者：Yeeman K. Ramtohul ; Cameron Black ; Chi-Chung Chan ; Sheldon Crane ; Jocelyne Guay ; Sé ; bastien Guiral ; Zheng Huang ; Renata Oballa ; Li-Jing Xu ; Lei Zhang ; Chun Sing Li
• 关键词：SCD inhibitors ; Desaturation index ; Body weight gain prevention ; Insulin and glucose sensitivity
• 刊名：Bioorganic and Medicinal Chemistry Letters
• 出版年：2010
• 出版时间：1 March 2010
• 年：2010
• 卷：20
• 期：5
• 页码：1593-1597
• 全文大小：1736 K

文摘

Elevated stearoyl-CoA desaturase (SCD) activity has been linked to a number of metabolic disorders including obesity and type II diabetes. Compound 3j, a potent SCD inhibitor (human HepG2 IC₅₀ = 1 nM) was identified from the optimization of a lead thiazole compound MF-152 with over 100-fold improvement in potency. In a 4-week chronic oral dosing at 0.2 mg/kg, 3j gave a robust 24 % prevention of body weight gain in mice fed on a high fat diet accompanied with an improved metabolic profile on insulin and glucose levels.