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.
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页数：15
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