Pyrazolo-[1,5-a]-1,3,5-triazine corticotropin-releasing factor (CRF) receptor ligands

Paul J Gilligan; Beverly K Folmer; Richard A Hartz; Stephanie Koch; Kausik K Nanda; Stephen Andreuski; Lawrence Fitzgerald; Keith Miller; William J Marshall

doi:10.1016/s0968-0896(03)00398-5

Pyrazolo-[1,5-a]-1,3,5-triazine corticotropin-releasing factor (CRF) receptor ligands

Bioorg Med Chem. 2003 Sep 1;11(18):4093-102. doi: 10.1016/s0968-0896(03)00398-5.

Authors

Paul J Gilligan¹, Beverly K Folmer, Richard A Hartz, Stephanie Koch, Kausik K Nanda, Stephen Andreuski, Lawrence Fitzgerald, Keith Miller, William J Marshall

Affiliation

¹ Bristol-Myers Squibb Co., Discovery Chemistry Department and E.I. DuPont de Nemours and Co., Central Research and Development Department, Experimental Station, Wilmington, DE 19880-0500, USA. [email protected]

PMID: 12927871
DOI: 10.1016/s0968-0896(03)00398-5

Abstract

The syntheses and rat CRF receptor binding affinities of 'retro-pyrazolotriazine' corticotropin-releasing factor (CRF) ligands 4 are reported. Some have high affinity for rat CRF receptors (K(i)< or =10 nM). The data provide additional support for the hypothesis that it is possible to interchange isosteric cores with similar electronic properties in the design of high-affinity CRF receptor ligands, provided the peripheral pharmacophore elements are maintained in the same three-dimensional array.

MeSH terms

Animals
Binding Sites
Cell Membrane / drug effects
Cell Membrane / metabolism
Corticotropin-Releasing Hormone / chemistry
Corticotropin-Releasing Hormone / pharmacology
In Vitro Techniques
Ligands
Models, Molecular
Molecular Structure
Pyrazoles / chemistry*
Rats
Receptors, Corticotropin-Releasing Hormone / classification
Receptors, Corticotropin-Releasing Hormone / drug effects*
Triazines / chemical synthesis*
Triazines / pharmacology

Substances

Ligands
Pyrazoles
Receptors, Corticotropin-Releasing Hormone
Triazines
Corticotropin-Releasing Hormone