Department of Chemistry, MSD, Newhouse, Lanarkshire, UK.
Bioorg Med Chem Lett. 2011 Mar 15;21(6):1871-5. doi: 10.1016/j.bmcl.2010.12.081. Epub 2010 Dec 21.
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.
描述了一系列新型血管加压素 V1b(V3)拮抗剂的合成和构效关系(SAR)。已经鉴定出 2-(4-氧代-2-芳基-喹唑啉-3(4H)-基)乙酰胺，它们对 V1b 受体具有低纳摩尔亲和力，并且相对于相关受体 V1a、V2 和催产素(OT)具有良好的选择性。优化后的化合物 12j 在 HPA 功能障碍的机制模型中表现出良好的药代动力学特性和活性。
