Patent of the Week - Vasopressin Inhibitors

A series of V3 antagonists were disclosed in patent 7807686 by Organon, which after a couple of mergers (what's new) is now part of the Merck/ Merck Sharp Dohme organization. The compounds share a common scaffold as shown on the left.

The compounds are aimed to CNS disorders which are characterized by abnormal hypothalamo-pituitary-adrenal axis negative feedback mechanisms, among them depression. V₃ receptor does play a functional role in control of pituitary adrenocorticotropic hormone release. The V_1a receptor, predominantly found on liver and vascular tissue and the V₂ receptor, predominantly found on kidney tissue have peripheral activity. Interaction at these receptors mediate the pressor and antidiuretic actions of Vasopressin.Only a qualitative sense of the affinity is provided.