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

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...

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Autores principales: Wang, Xinran, Hao, Lijuan, Xu, Xuanqi, Li, Wei, Liu, Chunchi, Zhao, Dongmei, Cheng, Maosheng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2017
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6151529/
https://www.ncbi.nlm.nih.gov/pubmed/28972557
http://dx.doi.org/10.3390/molecules22101658
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author Wang, Xinran
Hao, Lijuan
Xu, Xuanqi
Li, Wei
Liu, Chunchi
Zhao, Dongmei
Cheng, Maosheng
author_facet Wang, Xinran
Hao, Lijuan
Xu, Xuanqi
Li, Wei
Liu, Chunchi
Zhao, Dongmei
Cheng, Maosheng
author_sort Wang, Xinran
collection PubMed
description 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 (IC(50) = 0.38 ± 0.08 μM) in vitro. Furthermore, compound 17 was selected for an in vitro metabolic stability study.
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spelling pubmed-61515292018-11-13 Design, Synthesis and Biological Evaluation of N,N-Substituted Amine Derivatives as Cholesteryl Ester Transfer Protein Inhibitors Wang, Xinran Hao, Lijuan Xu, Xuanqi Li, Wei Liu, Chunchi Zhao, Dongmei Cheng, Maosheng Molecules Article 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 (IC(50) = 0.38 ± 0.08 μM) in vitro. Furthermore, compound 17 was selected for an in vitro metabolic stability study. MDPI 2017-10-03 /pmc/articles/PMC6151529/ /pubmed/28972557 http://dx.doi.org/10.3390/molecules22101658 Text en © 2017 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Wang, Xinran
Hao, Lijuan
Xu, Xuanqi
Li, Wei
Liu, Chunchi
Zhao, Dongmei
Cheng, Maosheng
Design, Synthesis and Biological Evaluation of N,N-Substituted Amine Derivatives as Cholesteryl Ester Transfer Protein Inhibitors
title Design, Synthesis and Biological Evaluation of N,N-Substituted Amine Derivatives as Cholesteryl Ester Transfer Protein Inhibitors
title_full Design, Synthesis and Biological Evaluation of N,N-Substituted Amine Derivatives as Cholesteryl Ester Transfer Protein Inhibitors
title_fullStr Design, Synthesis and Biological Evaluation of N,N-Substituted Amine Derivatives as Cholesteryl Ester Transfer Protein Inhibitors
title_full_unstemmed Design, Synthesis and Biological Evaluation of N,N-Substituted Amine Derivatives as Cholesteryl Ester Transfer Protein Inhibitors
title_short Design, Synthesis and Biological Evaluation of N,N-Substituted Amine Derivatives as Cholesteryl Ester Transfer Protein Inhibitors
title_sort design, synthesis and biological evaluation of n,n-substituted amine derivatives as cholesteryl ester transfer protein inhibitors
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6151529/
https://www.ncbi.nlm.nih.gov/pubmed/28972557
http://dx.doi.org/10.3390/molecules22101658
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