Arginine vasopressin (AVP) is a neuropeptide that plays an important role in the neuroendocrine and behavioral responses to stressors. Previous reports have indicated that antagonism of an AVP receptor subtype V1b receptor elicited antidepressant- and anxiolytic-like effects in animal models. Here, we present the design, synthesis, and SAR of novel V1b receptor antagonists, 1,2,4-triazol-3-one derivatives, which were optimized with a focus on balance between V1b receptor binding affinity and liver metabolic stability. These efforts led to the discovery of a potent and selective V1b receptor antagonist THY1773 that showed promise as a drug candidate for augmentation of antidepressant therapy in a recent clinical trial for patients who had inadequate response to current antidepressant treatment.

Discovery of a novel V1b receptor antagonist THY1773 for potential treatment of depression

Macromolecular Chemistry: The Second Century

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ACS Spring 2020 National Meeting & Expo

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.