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.
Luthin
D R
DR
Alanex Corporation, A Subsidiary of Agouron Pharmaceuticals, Inc., San Diego, CA 92121, USA.
Rabinovich
A K
AK
Bhumralkar
D R
DR
Youngblood
K L
KL
Bychowski
R A
RA
Dhanoa
D S
DS
May
J M
JM
D000324:Adrenocorticotropic Hormone / Q000378:metabolism; D000818:Animals; D002264:Carboxylic Acids / Q000138:chemical synthesis* / Q000494:pharmacology; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D006801:Humans; D008297:Male; D010902:Pituitary Gland / Q000187:drug effects* / Q000378:metabolism; D011799:Quinazolines / Q000138:chemical synthesis* / Q000494:pharmacology; D051381:Rats; D018019:Receptors, Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors*; D014162:Transfection
D002264:Carboxylic Acids; D011799:Quinazolines; D018019:Receptors, Corticotropin-Releasing Hormone; C119128:oxo-7H-benzo(e)perimidine-4-carboxylic acid; D000324:Adrenocorticotropic Hormone; D000242:Cyclic AMP