Key Laboratory of Structure-Based Drug Design & Discovery of Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, China.
Department of Chemistry, University of Wisconsin-Madison, Madison, WI 53715, USA.
Molecules. 2017 Nov 7;22(11):1925. doi: 10.3390/molecules22111925.
Cholesteryl ester transfer protein (CETP) has been identified as a potential target for cardiovascular disease (CVD) for its important role in the reverse cholesteryl transfer (RCT) process. In our previous work, compound was discovered as a moderate CETP inhibitor. The replacement of the amide linker by heterocyclic aromatics and then a series of ,-substituted-4-arylthiazole-2-methylamine derivatives were designed by utilizing a conformational restriction strategy. Thirty-six compounds were synthesized and evaluated for their CETP inhibitory activities. Structure-activity relationship studies indicate that electron donor groups substituted ring A, and electron-withdrawing groups at the 4-position of ring B were critical for potency. Among these compounds, compound exhibited excellent CETP inhibitory activity (IC = 0.79 ± 0.02 μM) in vitro and showed an acceptable metabolic stability.
胆固醇酯转移蛋白 (CETP) 在胆固醇逆转运 (RCT) 过程中发挥重要作用，因此被确定为心血管疾病 (CVD) 的潜在治疗靶点。在我们之前的工作中，发现化合物 是一种中等强度的 CETP 抑制剂。本研究利用构象限制策略，通过用杂环芳烃取代酰胺键，设计并合成了一系列,-取代-4-芳基噻唑-2-甲胺衍生物。共合成了 36 个化合物，并对其 CETP 抑制活性进行了评价。构效关系研究表明，A 环中取代的供电子基团和 B 环 4 位取代的吸电子基团对于活性至关重要。在这些化合物中，化合物 表现出优异的 CETP 抑制活性（IC = 0.79 ± 0.02 μM），体外代谢稳定性良好。
