Purin-8-ones as corticotropin-releasing hormone (CRH-R1) receptor antagonists.
A series of purin-8-ones was prepared and discovered to have excellent binding affinity to the CRH-R1 receptor. Structure-activity studies focused on amine side-chain optimization, urea substitution and pyridyl isostere incorporation. Thus, the highly potent purin-8-ones show promise as a new class of potential anxiolytics and/or antidepressants.
Beck
J P
JP
DuPont Pharmaceuticals Company, Chemical and Physical Sciences, Wilmington, DE 19880-0500, USA.
Arvanitis
A G
AG
Curry
M A
MA
Rescinito
J T
JT
Fitzgerald
L W
LW
Gilligan
P J
PJ
Zaczek
R
R
Trainor
G L
GL
D014151:Anti-Anxiety Agents / Q000737:chemistry / Q000494:pharmacology; D000928:Antidepressive Agents / Q000737:chemistry / Q000494:pharmacology; D011688:Purinones / Q000737:chemistry / Q000494:pharmacology*; D018019:Receptors, Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship; D000099052:CRF Receptor, Type 1
D014151:Anti-Anxiety Agents; D000928:Antidepressive Agents; D011688:Purinones; D018019:Receptors, Corticotropin-Releasing Hormone; D000099052:CRF Receptor, Type 1