Potential CRF1R PET imaging agents: N-fluoroalkyl-8-(6-methoxy-2-methylpyridin-3-yl)-2,7-dimethyl-N-alkylpyrazolo[1,5-a][1,3,5]triazin-4-amines

Dmitry Zuev; Ronald J Mattson; Hong Huang; Gail K Mattson; Larisa Zueva; Julia M Nielsen; Edward S Kozlowski; Xiaohua Stella Huang; Dedong Wu; Qi Gao; Nicholas J Lodge; Joanne J Bronson; John E Macor

doi:10.1016/j.bmcl.2011.02.050

Potential CRF1R PET imaging agents: N-fluoroalkyl-8-(6-methoxy-2-methylpyridin-3-yl)-2,7-dimethyl-N-alkylpyrazolo[1,5-a][1,3,5]triazin-4-amines

Bioorg Med Chem Lett. 2011 Apr 15;21(8):2484-8. doi: 10.1016/j.bmcl.2011.02.050. Epub 2011 Feb 17.

Authors

Dmitry Zuev¹, Ronald J Mattson, Hong Huang, Gail K Mattson, Larisa Zueva, Julia M Nielsen, Edward S Kozlowski, Xiaohua Stella Huang, Dedong Wu, Qi Gao, Nicholas J Lodge, Joanne J Bronson, John E Macor

Affiliation

¹ Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492, USA. dmitry.zuev@bms.com

PMID: 21411322
DOI: 10.1016/j.bmcl.2011.02.050

Abstract

A series of N-fluoroalkyl-8-(6-methoxy-2-methylpyridin-3-yl)-2,7-dimethyl-N-alkylpyrazolo[1,5-a][1,3,5]triazin-4-amines were prepared and evaluated as potential CRF(1)R PET imaging agents. Optimization of their CRF(1)R binding potencies and octanol-phosphate buffer phase distribution coefficients resulted in discovery of analog 7e (IC(50)=6.5 nM, logD=3.5).

MeSH terms

Amines / chemical synthesis
Amines / chemistry*
Crystallography, X-Ray
Molecular Conformation
Positron-Emission Tomography
Pyrazoles / chemical synthesis
Pyrazoles / chemistry*
Receptors, Corticotropin-Releasing Hormone / chemistry*
Receptors, Corticotropin-Releasing Hormone / metabolism
Triazines / chemical synthesis
Triazines / chemistry*

Substances

Amines
Pyrazoles
Receptors, Corticotropin-Releasing Hormone
Triazines
CRF receptor type 1