Synthesis and Biological Activity of Oxo-7H-benzo[e]perimidine-4-carboxylic Acid Derivatives as Potent, Nonpeptide Corticotropin Releasing Factor (CRF) Receptor Antagonists.

A novel series of derivatives of oxo-7H-benzo[e]perimidine-4-carboxylic acid (I) potently displaced radioligand binding of 125I-CRF to both CRF1 and CRF2 receptors. The members of this series antagonized CRF-stimulated cAMP formation and CRF-stimulated corticotropin release from rat pituitary in vivo. These are the first nonpeptide antagonists to show activity at both CRF1 and CRF2 receptors.