title: Synthesis and oral efficacy of a 4-(butylethylamino)pyrrolo[2,3-d]pyrimidine: a centrally active corticotropin-releasing factor1 receptor antagonist.
abstract: 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.
authors.affiliation: Medicinal Chemistry Department, Pfizer Inc., Groton, Connecticut 06340, USA. yuhpyng_l_chen@groton.pfizer.com.
authors.forename: Y L
authors.initials: YL
authors.lastname: Chen
authors.forename: R S
authors.initials: RS
authors.lastname: Mansbach
authors.forename: S M
authors.initials: SM
authors.lastname: Winter
authors.forename: E
authors.initials: E
authors.lastname: Brooks
authors.forename: J
authors.initials: J
authors.lastname: Collins
authors.forename: M L
authors.initials: ML
authors.lastname: Corman
authors.forename: A R
authors.initials: AR
authors.lastname: Dunaiskis
authors.forename: W S
authors.initials: WS
authors.lastname: Faraci
authors.forename: R J
authors.initials: RJ
authors.lastname: Gallaschun
authors.forename: A
authors.initials: A
authors.lastname: Schmidt
authors.forename: D W
authors.initials: DW
authors.lastname: Schulz
mesh_terms: 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
chemical_list: D014151:Anti-Anxiety Agents; C101628:CP 154526; D011743:Pyrimidines; D011758:Pyrroles; D018019:Receptors, Corticotropin-Releasing Hormone