Department of Chemistry, MSD, Newhouse, Lanarkshire, UK.
Bioorg Med Chem Lett. 2011 Jun 15;21(12):3813-7. doi: 10.1016/j.bmcl.2011.04.022. Epub 2011 Apr 13.
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), V(2) and OT. Optimised compound 16 shows 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 V(1b)拮抗剂的合成和构效关系（SAR）。2-（6-氨甲基芳基-2-芳基-4-氧代喹唑啉-3（4H）-基）乙酰胺对 V(1b)受体具有低纳摩尔亲和力，对相关受体 V(1a)、V(2)和 OT 具有良好的选择性。优化后的化合物 16 在 HPA 功能障碍的机制模型中具有良好的药代动力学特性和活性。
