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Design, Synthesis, and Biological Evaluation of N,N-Disubstituted-4-arylthiazole-2-methylamine Derivatives as Cholesteryl Ester Transfer Inhibitors
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 li...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6150381/ https://www.ncbi.nlm.nih.gov/pubmed/29112169 http://dx.doi.org/10.3390/molecules22111925 |
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author | Wang, Xinran Lin, Xuehua Xu, Xuanqi Li, Wei Hao, Lijuan Liu, Chunchi Zhao, Dongmei Cheng, Maosheng |
author_facet | Wang, Xinran Lin, Xuehua Xu, Xuanqi Li, Wei Hao, Lijuan Liu, Chunchi Zhao, Dongmei Cheng, Maosheng |
author_sort | Wang, Xinran |
collection | PubMed |
description | 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 (IC(50) = 0.79 ± 0.02 μM) in vitro and showed an acceptable metabolic stability. |
format | Online Article Text |
id | pubmed-6150381 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-61503812018-11-13 Design, Synthesis, and Biological Evaluation of N,N-Disubstituted-4-arylthiazole-2-methylamine Derivatives as Cholesteryl Ester Transfer Inhibitors Wang, Xinran Lin, Xuehua Xu, Xuanqi Li, Wei Hao, Lijuan Liu, Chunchi Zhao, Dongmei Cheng, Maosheng Molecules Article 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 (IC(50) = 0.79 ± 0.02 μM) in vitro and showed an acceptable metabolic stability. MDPI 2017-11-07 /pmc/articles/PMC6150381/ /pubmed/29112169 http://dx.doi.org/10.3390/molecules22111925 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 Lin, Xuehua Xu, Xuanqi Li, Wei Hao, Lijuan Liu, Chunchi Zhao, Dongmei Cheng, Maosheng Design, Synthesis, and Biological Evaluation of N,N-Disubstituted-4-arylthiazole-2-methylamine Derivatives as Cholesteryl Ester Transfer Inhibitors |
title | Design, Synthesis, and Biological Evaluation of N,N-Disubstituted-4-arylthiazole-2-methylamine Derivatives as Cholesteryl Ester Transfer Inhibitors |
title_full | Design, Synthesis, and Biological Evaluation of N,N-Disubstituted-4-arylthiazole-2-methylamine Derivatives as Cholesteryl Ester Transfer Inhibitors |
title_fullStr | Design, Synthesis, and Biological Evaluation of N,N-Disubstituted-4-arylthiazole-2-methylamine Derivatives as Cholesteryl Ester Transfer Inhibitors |
title_full_unstemmed | Design, Synthesis, and Biological Evaluation of N,N-Disubstituted-4-arylthiazole-2-methylamine Derivatives as Cholesteryl Ester Transfer Inhibitors |
title_short | Design, Synthesis, and Biological Evaluation of N,N-Disubstituted-4-arylthiazole-2-methylamine Derivatives as Cholesteryl Ester Transfer Inhibitors |
title_sort | design, synthesis, and biological evaluation of n,n-disubstituted-4-arylthiazole-2-methylamine derivatives as cholesteryl ester transfer inhibitors |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6150381/ https://www.ncbi.nlm.nih.gov/pubmed/29112169 http://dx.doi.org/10.3390/molecules22111925 |
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