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

Molecules

Libao Xu³  Yang Zhang¹  Wenjie Dai⁴  Ying Wang¹  Dan Jiang²  Lili Wang²  Junhai Xiao²  Xiaohong Yang³ 

[1] Department of Immunology, School of Basic Medical Sciences, Key Laboratory of Medical Immunology, Ministry of Health, Peking University Health Science Center, Beijing 100191, China; E-Mails:;Laboratory of Computer-Aided Drug Design & Discovery, Beijing Institute of Pharmacology & Toxicology, Beijing 100850, China; E-Mails:;School of Pharmaceutical Sciences, Jilin University, Changchun 130021, China; E-Mails:;Shenyang Pharmaceutical University, 103 Wenhua Road, Shenhe District, Shenyang 110016, China; E-Mail:

关键词: antagonists;    pyrimidine amides;    synthesis;    structure-activity relationship;   

DOI  :  10.3390/molecules19033539

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2014 by the authors; licensee MDPI, Basel, Switzerland.