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Design, Synthesis and SAR Study of Novel Trisubstituted Pyrimidine Amide Derivatives as CCR4 Antagonists
The design, synthesis and structure-activity relationship studies of some novel trisubstituted pyrimidine amide derivatives prepared as CCR4 antagonists are described. The activities of these compounds were evaluated by the CCR4-MDC chemotaxis inhibition assay. Compound 1, which we have previously r...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6271259/ https://www.ncbi.nlm.nih.gov/pubmed/24662072 http://dx.doi.org/10.3390/molecules19033539 |
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author | Xu, Libao Zhang, Yang Dai, Wenjie Wang, Ying Jiang, Dan Wang, Lili Xiao, Junhai Yang, Xiaohong Li, Song |
author_facet | Xu, Libao Zhang, Yang Dai, Wenjie Wang, Ying Jiang, Dan Wang, Lili Xiao, Junhai Yang, Xiaohong Li, Song |
author_sort | Xu, Libao |
collection | PubMed |
description | The design, synthesis and structure-activity relationship studies of some novel trisubstituted pyrimidine amide derivatives prepared as CCR4 antagonists are described. The activities of these compounds were evaluated by the CCR4-MDC chemotaxis inhibition assay. Compound 1, which we have previously reported as a potent antagonist of CCR4, was employed as the positive control. The results indicated that most of the synthesized compounds exhibited some chemotaxis inhibition activity against CCR4. Of these new compounds, compounds 6c, 12a and 12b, with IC(50 )values of 0.064, 0.077 and 0.069 μM, respectively, showed higher or similar activity compared with compound 1 (IC(50) of 0.078 μM). These compounds provide a basis for further structural modifications. The systematic structure-activity relationship of these trisubstituted pyrimidine amide derivatives was discussed based on the obtained experimental data. The results from the SAR study may be useful for identifying more potent CCR4 antagonists. |
format | Online Article Text |
id | pubmed-6271259 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-62712592018-12-20 Design, Synthesis and SAR Study of Novel Trisubstituted Pyrimidine Amide Derivatives as CCR4 Antagonists Xu, Libao Zhang, Yang Dai, Wenjie Wang, Ying Jiang, Dan Wang, Lili Xiao, Junhai Yang, Xiaohong Li, Song Molecules Article The design, synthesis and structure-activity relationship studies of some novel trisubstituted pyrimidine amide derivatives prepared as CCR4 antagonists are described. The activities of these compounds were evaluated by the CCR4-MDC chemotaxis inhibition assay. Compound 1, which we have previously reported as a potent antagonist of CCR4, was employed as the positive control. The results indicated that most of the synthesized compounds exhibited some chemotaxis inhibition activity against CCR4. Of these new compounds, compounds 6c, 12a and 12b, with IC(50 )values of 0.064, 0.077 and 0.069 μM, respectively, showed higher or similar activity compared with compound 1 (IC(50) of 0.078 μM). These compounds provide a basis for further structural modifications. The systematic structure-activity relationship of these trisubstituted pyrimidine amide derivatives was discussed based on the obtained experimental data. The results from the SAR study may be useful for identifying more potent CCR4 antagonists. MDPI 2014-03-21 /pmc/articles/PMC6271259/ /pubmed/24662072 http://dx.doi.org/10.3390/molecules19033539 Text en © 2014 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 license (http://creativecommons.org/licenses/by/3.0/). |
spellingShingle | Article Xu, Libao Zhang, Yang Dai, Wenjie Wang, Ying Jiang, Dan Wang, Lili Xiao, Junhai Yang, Xiaohong Li, Song Design, Synthesis and SAR Study of Novel Trisubstituted Pyrimidine Amide Derivatives as CCR4 Antagonists |
title | Design, Synthesis and SAR Study of Novel Trisubstituted Pyrimidine Amide Derivatives as CCR4 Antagonists |
title_full | Design, Synthesis and SAR Study of Novel Trisubstituted Pyrimidine Amide Derivatives as CCR4 Antagonists |
title_fullStr | Design, Synthesis and SAR Study of Novel Trisubstituted Pyrimidine Amide Derivatives as CCR4 Antagonists |
title_full_unstemmed | Design, Synthesis and SAR Study of Novel Trisubstituted Pyrimidine Amide Derivatives as CCR4 Antagonists |
title_short | Design, Synthesis and SAR Study of Novel Trisubstituted Pyrimidine Amide Derivatives as CCR4 Antagonists |
title_sort | design, synthesis and sar study of novel trisubstituted pyrimidine amide derivatives as ccr4 antagonists |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6271259/ https://www.ncbi.nlm.nih.gov/pubmed/24662072 http://dx.doi.org/10.3390/molecules19033539 |
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