Heteroatom-linked indanylpyrazines are corticotropin releasing factor type-1 receptor antagonists

Jeffrey W Corbett; Mark R Rauckhorst; Fang Qian; Robert L Hoffman; Christopher S Knauer; Lawrence W Fitzgerald

doi:10.1016/j.bmcl.2007.09.008

Heteroatom-linked indanylpyrazines are corticotropin releasing factor type-1 receptor antagonists

Bioorg Med Chem Lett. 2007 Nov 15;17(22):6250-6. doi: 10.1016/j.bmcl.2007.09.008. Epub 2007 Sep 7.

Authors

Jeffrey W Corbett¹, Mark R Rauckhorst, Fang Qian, Robert L Hoffman, Christopher S Knauer, Lawrence W Fitzgerald

Affiliation

¹ Pfizer Global Research and Development, Eastern Point Road, Groton, CT 06340, USA. jeffrey.w.corbett@pfizer.com

PMID: 17888659
DOI: 10.1016/j.bmcl.2007.09.008

Abstract

Low nanomolar corticotropin releasing factor type-1 (CRF(1)) receptor antagonists containing unique indanylamines were identified from the heteroatom-linked pyrazine chemotype. The most potent indanylpyrazine had a K(i)=11+/-1 nM. The oxygen-linked pyrazinyl derivatives were prepared through a copper-catalyzed coupling of a pyridinone to a bromo- or iodopyrazine.

MeSH terms

Binding, Competitive / drug effects
Catalysis
Copper / chemistry
Drug Evaluation, Preclinical
Humans
Indans / chemistry*
Molecular Structure
Pyrazines / chemistry*
Pyrazines / metabolism
Pyrazines / pharmacology*
Pyridones / chemistry
Receptors, Corticotropin-Releasing Hormone / antagonists & inhibitors*
Receptors, Corticotropin-Releasing Hormone / metabolism
Structure-Activity Relationship

Substances

Indans
Pyrazines
Pyridones
Receptors, Corticotropin-Releasing Hormone
CRF receptor type 1
Copper