Design, Synthesis, and Biological Evaluation of N,N-Disubstituted-4-Arylthiazole-2-Methylamine Derivatives as Cholesteryl Ester Transfer Inhibitors

Molecules

Xuanqi Xu¹  Lijuan Hao²  Wei Li²  Maosheng Cheng²  Xinran Wang²  Chunchi Liu²  Xuehua Lin²  Dongmei Zhao² 

[1] Department of Chemistry, University of Wisconsin-Madison, Madison, WI 53715, USA;Key Laboratory of Structure-Based Drug Design & Discovery of Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, China;

关键词: synthesis;    N,N-disubstituted-4-arylthiazole-2-methylamine derivatives;    CETP inhibitors;   

DOI  :  10.3390/molecules22111925

来源: DOAJ

【 摘 要 】

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 5 was discovered as a moderate CETP inhibitor. The replacement of the amide linker by heterocyclic aromatics and then a series of N,N-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 30 exhibited excellent CETP inhibitory activity (IC50 = 0.79 ± 0.02 μM) in vitro and showed an acceptable metabolic stability.

【 授权许可】

Unknown