Potent and selective oxindole-based vasopressin 1b receptor antagonists with improved pharmacokinetic properties

Bioorg Med Chem Lett. 2011 Jun 15;21(12):3828-31. doi: 10.1016/j.bmcl.2011.03.012. Epub 2011 Mar 6.


Herein we report the discovery of a novel series of vasopressin 1b (V1b) receptor antagonists, starting from potent but metabolically labile oxindole SSR149415. Masking the proline N,N-dimethyl amide moiety as an oxazole and attaching a benzylic amine moiety to the northern phenyl ring resulted in potent and selective V1b receptor antagonists with improved metabolic stability and improved pharmacokinetic properties in rat. Compound 18c was found to be efficacious in a rat model of anti-depressant activity.

MeSH terms

  • Animals
  • Antidepressive Agents / chemical synthesis*
  • Antidepressive Agents / chemistry
  • Antidepressive Agents / pharmacokinetics*
  • Antidepressive Agents / pharmacology
  • Antidiuretic Hormone Receptor Antagonists*
  • Disease Models, Animal
  • Indoles / chemical synthesis*
  • Indoles / chemistry
  • Indoles / pharmacokinetics*
  • Indoles / pharmacology
  • Molecular Structure
  • Oxindoles
  • Protein Binding / drug effects
  • Rats


  • Antidepressive Agents
  • Antidiuretic Hormone Receptor Antagonists
  • Indoles
  • Oxindoles
  • 2-oxindole