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Molecules 2014, 19(3), 3539-3551; doi:10.3390/molecules19033539
Article

Design, Synthesis and SAR Study of Novel Trisubstituted Pyrimidine Amide Derivatives as CCR4 Antagonists

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Received: 26 January 2014; in revised form: 17 March 2014 / Accepted: 18 March 2014 / Published: 21 March 2014
(This article belongs to the Section Medicinal Chemistry)
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Abstract: 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 IC50 values of 0.064, 0.077 and 0.069 μM, respectively, showed higher or similar activity compared with compound 1 (IC50 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.
Keywords: antagonists; pyrimidine amides; synthesis; structure-activity relationship antagonists; pyrimidine amides; synthesis; structure-activity relationship
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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MDPI and ACS Style

Xu, L.; Zhang, Y.; Dai, W.; Wang, Y.; Jiang, D.; Wang, L.; Xiao, J.; Yang, X.; Li, S. Design, Synthesis and SAR Study of Novel Trisubstituted Pyrimidine Amide Derivatives as CCR4 Antagonists. Molecules 2014, 19, 3539-3551.

AMA Style

Xu L, Zhang Y, Dai W, Wang Y, Jiang D, Wang L, Xiao J, Yang X, Li S. Design, Synthesis and SAR Study of Novel Trisubstituted Pyrimidine Amide Derivatives as CCR4 Antagonists. Molecules. 2014; 19(3):3539-3551.

Chicago/Turabian Style

Xu, Libao; Zhang, Yang; Dai, Wenjie; Wang, Ying; Jiang, Dan; Wang, Lili; Xiao, Junhai; Yang, Xiaohong; Li, Song. 2014. "Design, Synthesis and SAR Study of Novel Trisubstituted Pyrimidine Amide Derivatives as CCR4 Antagonists." Molecules 19, no. 3: 3539-3551.


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