Design, Synthesis and Biological Evaluation of Novel Piperazine Derivatives as CCR5 Antagonists

By using a fragment-assembly strategy and bioisosteric-replacement principle, a series of novel piperazine derivatives were designed, synthesized, and evaluated for their cellular target-effector fusion activities and in vitro antiviral activities against HIV-1. Preliminary structure-activity relati...

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Detalles Bibliográficos
Autores principales: Liu, Tao, Weng, Zhiyong, Dong, Xiaowu, Chen, Linjie, Ma, Ling, Cen, Shan, Zhou, Naiming, Hu, Yongzhou
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Research Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3538727/
https://www.ncbi.nlm.nih.gov/pubmed/23308267
http://dx.doi.org/10.1371/journal.pone.0053636
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author Liu, Tao
Weng, Zhiyong
Dong, Xiaowu
Chen, Linjie
Ma, Ling
Cen, Shan
Zhou, Naiming
Hu, Yongzhou
author_facet Liu, Tao
Weng, Zhiyong
Dong, Xiaowu
Chen, Linjie
Ma, Ling
Cen, Shan
Zhou, Naiming
Hu, Yongzhou
author_sort Liu, Tao
collection PubMed
description By using a fragment-assembly strategy and bioisosteric-replacement principle, a series of novel piperazine derivatives were designed, synthesized, and evaluated for their cellular target-effector fusion activities and in vitro antiviral activities against HIV-1. Preliminary structure-activity relationships (SARs) of target compounds were concluded in this study, and five compounds were found to exhibited medium to potent CCR5 fusion activities with IC(50) values in low micromolar level. Among evaluated compounds, 23 h was found to be a CCR5 antagonist with an IC(50) value of 6.29 µM and an anti-HIV-1 inhibitor with an IC(50) value of 0.44 µM.
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spelling pubmed-35387272013-01-10 Design, Synthesis and Biological Evaluation of Novel Piperazine Derivatives as CCR5 Antagonists Liu, Tao Weng, Zhiyong Dong, Xiaowu Chen, Linjie Ma, Ling Cen, Shan Zhou, Naiming Hu, Yongzhou PLoS One Research Article By using a fragment-assembly strategy and bioisosteric-replacement principle, a series of novel piperazine derivatives were designed, synthesized, and evaluated for their cellular target-effector fusion activities and in vitro antiviral activities against HIV-1. Preliminary structure-activity relationships (SARs) of target compounds were concluded in this study, and five compounds were found to exhibited medium to potent CCR5 fusion activities with IC(50) values in low micromolar level. Among evaluated compounds, 23 h was found to be a CCR5 antagonist with an IC(50) value of 6.29 µM and an anti-HIV-1 inhibitor with an IC(50) value of 0.44 µM. Public Library of Science 2013-01-07 /pmc/articles/PMC3538727/ /pubmed/23308267 http://dx.doi.org/10.1371/journal.pone.0053636 Text en © 2013 Liu et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Liu, Tao
Weng, Zhiyong
Dong, Xiaowu
Chen, Linjie
Ma, Ling
Cen, Shan
Zhou, Naiming
Hu, Yongzhou
Design, Synthesis and Biological Evaluation of Novel Piperazine Derivatives as CCR5 Antagonists
title Design, Synthesis and Biological Evaluation of Novel Piperazine Derivatives as CCR5 Antagonists
title_full Design, Synthesis and Biological Evaluation of Novel Piperazine Derivatives as CCR5 Antagonists
title_fullStr Design, Synthesis and Biological Evaluation of Novel Piperazine Derivatives as CCR5 Antagonists
title_full_unstemmed Design, Synthesis and Biological Evaluation of Novel Piperazine Derivatives as CCR5 Antagonists
title_short Design, Synthesis and Biological Evaluation of Novel Piperazine Derivatives as CCR5 Antagonists
title_sort design, synthesis and biological evaluation of novel piperazine derivatives as ccr5 antagonists
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3538727/
https://www.ncbi.nlm.nih.gov/pubmed/23308267
http://dx.doi.org/10.1371/journal.pone.0053636
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