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

Molecules

Shuai Mu²  Ying Liu¹  Min Gong¹  Deng-Ke Liu¹ 

[1] Tianjin Key Laboratory of Molecular Design and Drug Discovery, Tianjin Institute of Pharmaceutical Research, Tianjin 300193, China; E-Mails:;School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, China; E-Mail:

关键词: substituted desloratadine;    synthesis;    arginine vasopressin receptor antagonists;    biological activity;   

DOI  :  10.3390/molecules19022694

来源: mdpi

【 摘 要 】

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 ¹H-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.

【 授权许可】

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