title: Synthesis and biological evaluation of substituted desloratadines as potent arginine vasopressin V2 receptor antagonists.
abstract: 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.
authors.affiliation: School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, China. mushuai2005@163.com.
authors.forename: Shuai
authors.initials: S
authors.lastname: Mu
authors.affiliation: Tianjin Key Laboratory of Molecular Design and Drug Discovery, Tianjin Institute of Pharmaceutical Research, Tianjin 300193, China. liuy6@tjipr.com.
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Tianjin Key Laboratory of Molecular Design and Drug Discovery, Tianjin Institute of Pharmaceutical Research, Tianjin 300193, China. gongm@tjipr.com.
authors.forename: Min
authors.initials: M
authors.lastname: Gong
authors.affiliation: Tianjin Key Laboratory of Molecular Design and Drug Discovery, Tianjin Institute of Pharmaceutical Research, Tianjin 300193, China. liudk@tianjinipr.com.
authors.forename: Deng-Ke
authors.initials: DK
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Drug Delivery Technology and Pharmacokinetics, Tianjin Institute of Pharmaceutical Research, Tianjin 300193, China. liuchangxiao@163.com.
authors.forename: Chang-Xiao
authors.initials: CX
authors.lastname: Liu
mesh_terms: D000818:Animals; D065092:Antidiuretic Hormone Receptor Antagonists; D001681:Biological Assay; D002460:Cell Line; D006801:Humans; D017336:Loratadine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D051381:Rats; D017483:Receptors, Vasopressin / Q000378:metabolism; D013329:Structure-Activity Relationship; D014667:Vasopressins / Q000378:metabolism
chemical_list: C585768:AVPR2 protein, human; D065092:Antidiuretic Hormone Receptor Antagonists; D017483:Receptors, Vasopressin; D014667:Vasopressins; D017336:Loratadine; C121345:desloratadine