Design and synthesis of 3-(2-pyridyl)pyrazolo[1,5-a]pyrimidines as potent CRF1 receptor antagonists

Charles Q Huang; Keith M Wilcoxen; Dimitri E Grigoriadis; James R McCarthy; Chen Chen

doi:10.1016/j.bmcl.2004.05.056

Design and synthesis of 3-(2-pyridyl)pyrazolo[1,5-a]pyrimidines as potent CRF1 receptor antagonists

Bioorg Med Chem Lett. 2004 Aug 2;14(15):3943-7. doi: 10.1016/j.bmcl.2004.05.056.

Authors

Charles Q Huang¹, Keith M Wilcoxen, Dimitri E Grigoriadis, James R McCarthy, Chen Chen

Affiliation

¹ Department of Medicinal Chemistry and Department of Pharmacology, Neurocrine Biosciences, Inc., 10555 Science Center Drive, San Diego, CA 92129, USA. chuang@neurocrine.com

PMID: 15225703
DOI: 10.1016/j.bmcl.2004.05.056

Abstract

A series of 3-(2-pyridyl)pyrazolo[1,5-a]pyrimidines was designed and synthesized as antagonists for the corticotrophin-releasing factor-1 (CRF(1)) receptor. Several compounds such as 20c (K(i)=10 nM) exhibited good binding affinities at the CRF(1) receptor. In addition, 20c had adequate solubility in water.

MeSH terms

Drug Design
Kinetics
Models, Molecular
Molecular Structure
Pyrazoles / chemical synthesis*
Pyrazoles / chemistry
Pyrazoles / pharmacology
Pyrimidines / chemical synthesis*
Pyrimidines / chemistry
Pyrimidines / pharmacology
Receptors, Corticotropin-Releasing Hormone / antagonists & inhibitors*
Structure-Activity Relationship

Substances

4-(3-pentylamino)-2,7-dimethyl-8-(2-methyl-4-methoxyphenyl)pyrazolo(1,5-a)pyrimidine
Pyrazoles
Pyrimidines
Receptors, Corticotropin-Releasing Hormone
CRF receptor type 1