噻唑类似物作为强效硬脂酰辅酶 A 去饱和酶抑制剂的 SAR 和优化。
SAR and optimization of thiazole analogs as potent stearoyl-CoA desaturase inhibitors.
机构信息
Department of Medicinal Chemistry, Merck Frosst Centre for Therapeutic Research, 16711 TransCanada Hwy, Kirkland, Quebec, Canada H9H 3L1.
出版信息
Bioorg Med Chem Lett. 2010 Mar 1;20(5):1593-7. doi: 10.1016/j.bmcl.2010.01.083. Epub 2010 Jan 21.
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 IC(50)=1nM) 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 0.2mg/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.
硬脂酰辅酶 A 去饱和酶（SCD）活性升高与多种代谢紊乱有关，包括肥胖和 2 型糖尿病。化合物 3j 是一种有效的 SCD 抑制剂（人 HepG2 IC（50）=1nM），是通过对先导噻唑化合物 MF-152 的优化得到的，其效力提高了 100 多倍。在以 0.2mg/kg 进行的为期 4 周的慢性口服给药中，3j 使高脂饮食喂养的小鼠体重增加得到了强有力的 24%预防，同时改善了胰岛素和葡萄糖水平的代谢谱。
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