Arginine vasopressin (AVP) is a neuropeptide that plays a primary role in the neuroendcrine and behavioral responses to stressors. Previous reports have indicated that an AVP receptor subtype V1b receptor antagonist elicited antidepressant- and anxiolytic-like effects in animal model. In order to clarify the potential role of selective V1b receptor antagonists, we performed optimization of a 1,3-dihydro-2H-indol-2-one scaffold to identify original tool compounds for pharmacological evaluation. The compounds showed excellent antagonistic activity against the V1b receptor and have favorable pharmakokinetic profiles. A representative compound exhibited antidepressant- and anxiolytic effects in several animal models including forced swimming and social interaction test.   We will present the synthesis and SAR study of 1,3-dihydro-2H-indol-2-one derivatives, and in addition, the in vivo effects of the representative compounds in these animal models.

1,3-Dihydro-2<i>H</i>-indol-2-one derivatives as novel vasopressin V1b antagonists: Lead optimization and pharmacological effects of the potent V1b antagonists in animal models

244th National Meeting (2012)

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1,3-Dihydro-2H-indol-2-one derivatives as novel vasopressin V1b antagonists: Lead optimization and pharmacological effects of the potent V1b antagonists in animal models