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Molecules 2012, 17(8), 9961-9970; doi:10.3390/molecules17089961
Article

Design and Synthesis of a Series of Pyrido[2,3-d]pyrimidine Derivatives as CCR4 Antagonists

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Received: 26 June 2012; in revised form: 6 August 2012 / Accepted: 13 August 2012 / Published: 20 August 2012
(This article belongs to the Section Medicinal Chemistry)
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Abstract: A series of pyrido[2,3-d]pyrimidine derivatives were designed and synthesized based on known CC chemokine receptor 4 (CCR4) antagonists. The activities of all the newly synthesized compounds were evaluated using a chemotaxis inhibition assay. Compound 6b was proven to be a potent CCR4 antagonist that can block cell chemotaxis induced by macrophage-derived chemokine (MDC), thymus and activation regulated chemokine (TARC), and CKLF1, the natural ligands of CCR4. In addition, compound 6b is more effective than budesonide in the murine rhinitis model. The intravenous injection LD50 of compound 6b is 175 mg/kg and the oral LD50 is greater than 2,000 mg/kg.
Keywords: CC chemokine receptor 4 (CCR4) antagonists; CKLF1; TARC; MDC; inflammatory disease CC chemokine receptor 4 (CCR4) antagonists; CKLF1; TARC; MDC; inflammatory disease
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

Gong, H.; Qi, H.; Sun, W.; Zhang, Y.; Jiang, D.; Xiao, J.; Yang, X.; Wang, Y.; Li, S. Design and Synthesis of a Series of Pyrido[2,3-d]pyrimidine Derivatives as CCR4 Antagonists. Molecules 2012, 17, 9961-9970.

AMA Style

Gong H, Qi H, Sun W, Zhang Y, Jiang D, Xiao J, Yang X, Wang Y, Li S. Design and Synthesis of a Series of Pyrido[2,3-d]pyrimidine Derivatives as CCR4 Antagonists. Molecules. 2012; 17(8):9961-9970.

Chicago/Turabian Style

Gong, Hongwei; Qi, Hui; Sun, Wei; Zhang, Yang; Jiang, Dan; Xiao, Junhai; Yang, Xiaohong; Wang, Ying; Li, Song. 2012. "Design and Synthesis of a Series of Pyrido[2,3-d]pyrimidine Derivatives as CCR4 Antagonists." Molecules 17, no. 8: 9961-9970.


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