Synthesis and oral efficacy of a 4-(butylethylamino)pyrrolo[2,3-d]pyrimidine: a centrally active corticotropin-releasing factor1 receptor antagonist.
The syntheses of a centrally active nonpeptide CRF1 receptor antagonist 2, butylethyl[2,5-dimethyl-7-(2,4,6-trimethylphenyl)-7H-pyrrolo [2,3-d]pyrimidin-4-yl]amine (CP-154,526), and its analogs 11-14 and [3H]-2 are reported. The in vitro CRF1 receptor binding affinity in the series 2, the pharmacokinetic properties of 2 in rats, and the anxiolytic-like effects of orally administered 2 are presented.
Chen
Y L
YL
Medicinal Chemistry Department, Pfizer Inc., Groton, Connecticut 06340, USA. yuhpyng_l_chen@groton.pfizer.com.
Mansbach
R S
RS
Winter
S M
SM
Brooks
E
E
Collins
J
J
Corman
M L
ML
Dunaiskis
A R
AR
Faraci
W S
WS
Gallaschun
R J
RJ
Schmidt
A
A
Schulz
D W
DW
D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology; D005239:Fear; D008297:Male; D015394:Molecular Structure; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D011758:Pyrroles / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018019:Receptors, Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013216:Reflex, Startle / Q000187:drug effects; D013329:Structure-Activity Relationship
D014151:Anti-Anxiety Agents; C101628:CP 154526; D011743:Pyrimidines; D011758:Pyrroles; D018019:Receptors, Corticotropin-Releasing Hormone