Substituted tetraazaacenaphthylenes as potent CRF1 receptor antagonists for the treatment of depression and anxiety

Bioorg Med Chem Lett. 2005 Aug 15;15(16):3713-6. doi: 10.1016/j.bmcl.2005.05.040.


Two isomers of the hexahydro-tetraazaacenaphthylene templates (1 and 2) are presented as novel, potent, and selective corticotropin releasing factor-1 (CRF1) receptor antagonists. In this paper, we report the affinity and SAR of a series of compounds, as well as pharmacokinetic characterization of a chosen set. The anxiolitic activity of a selected example (2ba) in the rat pup vocalization model is also presented.

MeSH terms

  • Acenaphthenes / chemical synthesis
  • Acenaphthenes / pharmacology*
  • Acenaphthenes / therapeutic use*
  • Animals
  • Anxiety / drug therapy*
  • Depression / drug therapy*
  • Disease Models, Animal
  • Drug Evaluation, Preclinical
  • Molecular Structure
  • Rats
  • Rats, Wistar
  • Receptors, Corticotropin-Releasing Hormone / antagonists & inhibitors*
  • Structure-Activity Relationship


  • Acenaphthenes
  • Receptors, Corticotropin-Releasing Hormone
  • CRF receptor type 1