Synthesis and biological activity of oxo-7H-benzo[e]perimidine-4-carboxylic acid derivatives as potent, nonpeptide corticotropin releasing factor (CRF) receptor antagonists

D R Luthin; A K Rabinovich; D R Bhumralkar; K L Youngblood; R A Bychowski; D S Dhanoa; J M May

doi:10.1016/s0960-894x(99)00075-x

Synthesis and biological activity of oxo-7H-benzo[e]perimidine-4-carboxylic acid derivatives as potent, nonpeptide corticotropin releasing factor (CRF) receptor antagonists

Bioorg Med Chem Lett. 1999 Mar 8;9(5):765-70. doi: 10.1016/s0960-894x(99)00075-x.

Authors

D R Luthin¹, A K Rabinovich, D R Bhumralkar, K L Youngblood, R A Bychowski, D S Dhanoa, J M May

Affiliation

¹ Alanex Corporation, A Subsidiary of Agouron Pharmaceuticals, Inc., San Diego, CA 92121, USA.

PMID: 10201844
DOI: 10.1016/s0960-894x(99)00075-x

Abstract

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.

MeSH terms

Adrenocorticotropic Hormone / metabolism
Animals
Carboxylic Acids / chemical synthesis*
Carboxylic Acids / pharmacology
Cells, Cultured
Cyclic AMP / metabolism
Humans
Male
Pituitary Gland / drug effects*
Pituitary Gland / metabolism
Quinazolines / chemical synthesis*
Quinazolines / pharmacology
Rats
Receptors, Corticotropin-Releasing Hormone / antagonists & inhibitors*
Transfection

Substances

Carboxylic Acids
Quinazolines
Receptors, Corticotropin-Releasing Hormone
oxo-7H-benzo(e)perimidine-4-carboxylic acid
Adrenocorticotropic Hormone
Cyclic AMP