Design, Synthesis and Biological Evaluation of N,N-Substituted Amine Derivatives as Cholesteryl Ester Transfer Protein Inhibitors

被引：0

作者：

Wang, Xinran ^{[1
]}

Hao, Lijuan ^{[1
]}

Xu, Xuanqi ^{[2
]}

Li, Wei ^{[1
]}

Liu, Chunchi ^{[1
]}

Zhao, Dongmei ^{[1
]}

Cheng, Maosheng ^{[1
]}

机构：

[1] Shenyang Pharmaceut Univ, Key Lab Struct Based Drug Design & Discovery, Minist Educ, Shenyang 110016, Liaoning, Peoples R China

[2] Univ Wisconsin, Dept Chem, Madison, WI 53715 USA

来源：

MOLECULES | 2017年 / 22卷 / 10期

基金：

中国国家自然科学基金;

关键词：

synthesis; N; N-substituted amine derivatives; CETP inhibitors; HDL-C; CORONARY-HEART-DISEASE; RANDOMIZED CLINICAL-TRIAL; HIGH-RISK; LDL CHOLESTEROL; HDL CHOLESTEROL; CETP INHIBITOR; DOUBLE-BLIND; TORCETRAPIB; DALCETRAPIB; ATHEROSCLEROSIS;

D O I：

10.3390/molecules22101658

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

N,N-Substituted amine derivatives were designed by utilizing a bioisosterism strategy. Consequently, twenty-two compounds were synthesized and evaluated for their inhibitory activity against CETP. Structure-activity relationship (SAR) studies indicate that hydrophilic groups at the 2-position of the tetrazole and 3,5-bistrifluoromethyl groups on the benzene ring provide important contributions to the potency. Among these compounds, compound 17 exhibited excellent CETP inhibitory activity (IC50 = 0.38 +/- 0.08 mu M) in vitro. Furthermore, compound 17 was selected for an in vitro metabolic stability study.

引用

页数：15

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