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Synthesis and Biological Evaluation of Substituted Desloratadines as Potent Arginine Vasopressin V2 Receptor Antagonists

Twenty-one non-peptide substituted desloratadine class compounds were synthesized as novel arginine vasopressin receptor antagonists from desloratadine via successive acylation, reduction and acylation reactions. Their structures were characterized by (1)H-NMR and HRMS, their biological activity was...

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Detalles Bibliográficos
Autores principales: Mu, Shuai, Liu, Ying, Gong, Min, Liu, Deng-Ke, Liu, Chang-Xiao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6271649/
https://www.ncbi.nlm.nih.gov/pubmed/24566331
http://dx.doi.org/10.3390/molecules19022694
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author Mu, Shuai
Liu, Ying
Gong, Min
Liu, Deng-Ke
Liu, Chang-Xiao
author_facet Mu, Shuai
Liu, Ying
Gong, Min
Liu, Deng-Ke
Liu, Chang-Xiao
author_sort Mu, Shuai
collection PubMed
description Twenty-one non-peptide substituted desloratadine class compounds were synthesized as novel arginine vasopressin receptor antagonists from desloratadine via successive acylation, reduction and acylation reactions. Their structures were characterized by (1)H-NMR and HRMS, their biological activity was evaluated by in vitro and in vivo studies. The in vitro binding assay and cAMP accumulation assay indicated that these compounds are potent selective V2 receptor antagonists. Among them compounds 1n, 1t and 1v exhibited both high affinity and promising selectivity for V2 receptors. The in vivo diuretic assay demonstrated that 1t presented remarkable diuretic activity. In conclusion, 1t is a potent novel AVP V2 receptor antagonist candidate.
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spelling pubmed-62716492018-12-20 Synthesis and Biological Evaluation of Substituted Desloratadines as Potent Arginine Vasopressin V2 Receptor Antagonists Mu, Shuai Liu, Ying Gong, Min Liu, Deng-Ke Liu, Chang-Xiao Molecules Article Twenty-one non-peptide substituted desloratadine class compounds were synthesized as novel arginine vasopressin receptor antagonists from desloratadine via successive acylation, reduction and acylation reactions. Their structures were characterized by (1)H-NMR and HRMS, their biological activity was evaluated by in vitro and in vivo studies. The in vitro binding assay and cAMP accumulation assay indicated that these compounds are potent selective V2 receptor antagonists. Among them compounds 1n, 1t and 1v exhibited both high affinity and promising selectivity for V2 receptors. The in vivo diuretic assay demonstrated that 1t presented remarkable diuretic activity. In conclusion, 1t is a potent novel AVP V2 receptor antagonist candidate. MDPI 2014-02-24 /pmc/articles/PMC6271649/ /pubmed/24566331 http://dx.doi.org/10.3390/molecules19022694 Text en © 2014 by the authors. Licensee MDPI, Basel, Switzerland. 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
Mu, Shuai
Liu, Ying
Gong, Min
Liu, Deng-Ke
Liu, Chang-Xiao
Synthesis and Biological Evaluation of Substituted Desloratadines as Potent Arginine Vasopressin V2 Receptor Antagonists
title Synthesis and Biological Evaluation of Substituted Desloratadines as Potent Arginine Vasopressin V2 Receptor Antagonists
title_full Synthesis and Biological Evaluation of Substituted Desloratadines as Potent Arginine Vasopressin V2 Receptor Antagonists
title_fullStr Synthesis and Biological Evaluation of Substituted Desloratadines as Potent Arginine Vasopressin V2 Receptor Antagonists
title_full_unstemmed Synthesis and Biological Evaluation of Substituted Desloratadines as Potent Arginine Vasopressin V2 Receptor Antagonists
title_short Synthesis and Biological Evaluation of Substituted Desloratadines as Potent Arginine Vasopressin V2 Receptor Antagonists
title_sort synthesis and biological evaluation of substituted desloratadines as potent arginine vasopressin v2 receptor antagonists
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6271649/
https://www.ncbi.nlm.nih.gov/pubmed/24566331
http://dx.doi.org/10.3390/molecules19022694
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