Synthesis and SAR studies of novel 2-(6-aminomethylaryl-2-aryl-4-oxo-quinazolin-3(4H)-yl)acetamide Vasopressin V_1b receptor antagonists

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• 作者：Susan E. Napier^a ; ; ^{susan.napier@spcorp.com"" rel=""nofollow} ; ^{susannapier67@googlemail.com"" rel=""nofollow} ; Jeffrey J. Letourneau^b ; ^{Jeffrey_letourneau@yahoo.com"" rel=""nofollow} ; Nasrin Ansari^b ; Douglas S. Auld^b ; James Baker^c ; Stuart Best^c ; Leigh Campbell-Wan^c ; Ray Chan^b ; Mark Craighead^d ; Hema Desai^b ; Koc-Kan Ho^b ; Cliona MacSweeney^c ; Rachel Milne^d ; J. Richard Morphy^a ; Irina Neagu^b ; Michael H.J. Ohlmeyer^b ; Jack Pick^a ; Jeremy Presland^a ; Chris Riviello^b ; Heather A. Zanetakos^b ; Jiuqiao Zhao^b ; Maria L. Webb^b
• 关键词：V1b ; HPA ; Antagonist
• 刊名：Bioorganic and Medicinal Chemistry Letters
• 出版年：2011
• 出版时间：15 June 2011
• 年：2011
• 卷：21
• 期：12
• 页码：3813-3817
• 全文大小：1929 K

文摘

Synthesis and structure–activity relationships (SAR) of a novel series of vasopressin V_1b antagonists are described. 2-(6-Aminomethylaryl-2-aryl-4-oxo-quinazolin-3(4H)-yl)acetamide have been identified with low nanomolar affinity for the V_1b receptor and good selectivity with respect to related receptors V_1a, V₂ and OT. Optimised compound 16 shows a good pharmacokinetic profile and activity in a mechanistic model of HPA dysfunction.