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ID: ALA1681774

Journal: Bioorg Med Chem Lett

Title: Synthesis and SAR studies of novel 2-(4-oxo-2-aryl-quinazolin-3(4H)-yl)acetamide vasopressin V1b receptor antagonists.

Authors: Napier SE, Letourneau JJ, Ansari N, Auld DS, Baker J, Best S, Campbell-Wan L, Chan JH, Craighead M, Desai H, Goan KA, Ho KK, Hulskotte EG, MacSweeney CP, Milne R, Morphy JR, Neagu I, Ohlmeyer MH, Peeters AW, Presland J, Riviello C, Ruigt GS, Thomson FJ, Zanetakos HA, Zhao J, Webb ML.

Abstract: Synthesis and structure-activity relationships (SAR) of a novel series of vasopressin V(1b) (V(3)) antagonists are described. 2-(4-Oxo-2-aryl-quinazolin-3(4H)-yl)acetamides have been identified with low nanomolar affinity for the V(1b) receptor and good selectivity with respect to related receptors V(1a), V(2) and oxytocin (OT). Optimised compound 12j demonstrates a good pharmacokinetic profile and activity in a mechanistic model of HPA dysfunction.

CiteXplore: 21353540

DOI: 10.1016/j.bmcl.2010.12.081