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

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 tha...

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Autores principales: Gong, Hongwei, Qi, Hui, Sun, Wei, Zhang, Yang, Jiang, Dan, Xiao, Junhai, Yang, Xiaohong, Wang, Ying, Li, Song
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2012
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6268086/
https://www.ncbi.nlm.nih.gov/pubmed/22907157
http://dx.doi.org/10.3390/molecules17089961
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author Gong, Hongwei
Qi, Hui
Sun, Wei
Zhang, Yang
Jiang, Dan
Xiao, Junhai
Yang, Xiaohong
Wang, Ying
Li, Song
author_facet Gong, Hongwei
Qi, Hui
Sun, Wei
Zhang, Yang
Jiang, Dan
Xiao, Junhai
Yang, Xiaohong
Wang, Ying
Li, Song
author_sort Gong, Hongwei
collection PubMed
description 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 LD(50) of compound 6b is 175 mg/kg and the oral LD(50) is greater than 2,000 mg/kg.
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spelling pubmed-62680862018-12-12 Design and Synthesis of a Series of Pyrido[2,3-d]pyrimidine Derivatives as CCR4 Antagonists Gong, Hongwei Qi, Hui Sun, Wei Zhang, Yang Jiang, Dan Xiao, Junhai Yang, Xiaohong Wang, Ying Li, Song Molecules Article 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 LD(50) of compound 6b is 175 mg/kg and the oral LD(50) is greater than 2,000 mg/kg. MDPI 2012-08-20 /pmc/articles/PMC6268086/ /pubmed/22907157 http://dx.doi.org/10.3390/molecules17089961 Text en © 2012 by the authors; licensee MDPI, Basel, Switzerland. http://creativecommons.org/licenses/by/3.0/ 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
Gong, Hongwei
Qi, Hui
Sun, Wei
Zhang, Yang
Jiang, Dan
Xiao, Junhai
Yang, Xiaohong
Wang, Ying
Li, Song
Design and Synthesis of a Series of Pyrido[2,3-d]pyrimidine Derivatives as CCR4 Antagonists
title Design and Synthesis of a Series of Pyrido[2,3-d]pyrimidine Derivatives as CCR4 Antagonists
title_full Design and Synthesis of a Series of Pyrido[2,3-d]pyrimidine Derivatives as CCR4 Antagonists
title_fullStr Design and Synthesis of a Series of Pyrido[2,3-d]pyrimidine Derivatives as CCR4 Antagonists
title_full_unstemmed Design and Synthesis of a Series of Pyrido[2,3-d]pyrimidine Derivatives as CCR4 Antagonists
title_short Design and Synthesis of a Series of Pyrido[2,3-d]pyrimidine Derivatives as CCR4 Antagonists
title_sort design and synthesis of a series of pyrido[2,3-d]pyrimidine derivatives as ccr4 antagonists
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6268086/
https://www.ncbi.nlm.nih.gov/pubmed/22907157
http://dx.doi.org/10.3390/molecules17089961
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