Synthesis and oral efficacy of a 4-(butylethylamino)pyrrolo[2,3-d]pyrimidine: a centrally active corticotropin-releasing factor1 receptor antagonist

Y L Chen; R S Mansbach; S M Winter; E Brooks; J Collins; M L Corman; A R Dunaiskis; W S Faraci; R J Gallaschun; A Schmidt; D W Schulz

doi:10.1021/jm960861b

Synthesis and oral efficacy of a 4-(butylethylamino)pyrrolo[2,3-d]pyrimidine: a centrally active corticotropin-releasing factor1 receptor antagonist

J Med Chem. 1997 May 23;40(11):1749-54. doi: 10.1021/jm960861b.

Authors

Y L Chen¹, R S Mansbach, S M Winter, E Brooks, J Collins, M L Corman, A R Dunaiskis, W S Faraci, R J Gallaschun, A Schmidt, D W Schulz

Affiliation

¹ Medicinal Chemistry Department, Pfizer Inc., Groton, Connecticut 06340, USA. yuhpyng_l_chen@groton.pfizer.com.

PMID: 9171885
DOI: 10.1021/jm960861b

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.

MeSH terms

Animals
Anti-Anxiety Agents / pharmacology
Fear
Male
Molecular Structure
Pyrimidines / chemical synthesis*
Pyrimidines / pharmacokinetics
Pyrimidines / pharmacology
Pyrroles / chemical synthesis*
Pyrroles / pharmacokinetics
Pyrroles / pharmacology
Rats
Rats, Sprague-Dawley
Receptors, Corticotropin-Releasing Hormone / antagonists & inhibitors*
Receptors, Corticotropin-Releasing Hormone / metabolism
Reflex, Startle / drug effects
Structure-Activity Relationship

Substances

Anti-Anxiety Agents
CP 154526
Pyrimidines
Pyrroles
Receptors, Corticotropin-Releasing Hormone