Back to Search
Start Over
Synthesis, structure-activity relationships, and in vivo evaluation of N3-phenylpyrazinones as novel corticotropin-releasing factor-1 (CRF1) receptor antagonists
- Source :
- Journal of medicinal chemistry. 52(14)
- Publication Year :
- 2009
-
Abstract
- Evidence suggests that corticotropin-releasing factor-1 (CRF(1)) receptor antagonists may offer therapeutic potential for the treatment of diseases associated with elevated levels of CRF such as anxiety and depression. A pyrazinone-based chemotype of CRF(1) receptor antagonists was discovered. Structure-activity relationship studies led to the identification of numerous potent analogues including 12p, a highly potent and selective CRF(1) receptor antagonist with an IC(50) value of 0.26 nM. The pharmacokinetic properties of 12p were assessed in rats and Cynomolgus monkeys. Compound 12p was efficacious in the defensive withdrawal test (an animal model of anxiety) in rats. The synthesis, structure-activity relationships and in vivo properties of compounds within the pyrazinone chemotype are described.
- Subjects :
- Male
Chemistry
medicine.drug_class
Antagonist
Pharmacology
Receptor antagonist
Receptors, Corticotropin-Releasing Hormone
In vitro
Rats
Rats, Sprague-Dawley
Macaca fascicularis
Structure-Activity Relationship
Pharmacokinetics
In vivo
Cell culture
Cell Line, Tumor
Pyrazines
Drug Discovery
medicine
Molecular Medicine
Structure–activity relationship
Animals
Humans
Receptor
Subjects
Details
- ISSN :
- 15204804
- Volume :
- 52
- Issue :
- 14
- Database :
- OpenAIRE
- Journal :
- Journal of medicinal chemistry
- Accession number :
- edsair.doi.dedup.....acf6fce28b1a442887f7f1287fe1f47b