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Bioorg Med Chem Lett. 2015 Nov 15;25(22):5111-4. doi: 10.1016/j.bmcl.2015.10.010. Epub 2015 Oct 8.

Synthesis, binding affinity, radiolabeling, and microPET evaluation of 4-(2-substituted-4-substituted)-8-(dialkylamino)-6-methyl-1-substituted-3,4-dihydropyrido[2,3-b]pyrazin-2(1H)-ones as ligands for brain corticotropin-releasing factor type-1 (CRF1) receptors.

Author information

1
Center for Systems Imaging, Department of Radiology and Imaging Sciences, Emory University, WWHC 209, 1841 Clifton Rd NE, Atlanta, GA 30329, USA. Electronic address: jstehou@emory.edu.
2
Department of Psychiatry and Behavioral Sciences, Emory University, Atlanta, GA, USA.
3
Center for Systems Imaging, Department of Radiology and Imaging Sciences, Emory University, WWHC 209, 1841 Clifton Rd NE, Atlanta, GA 30329, USA.
4
Psychiatric Research Institute, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
5
Center for Systems Imaging, Department of Radiology and Imaging Sciences, Emory University, WWHC 209, 1841 Clifton Rd NE, Atlanta, GA 30329, USA; Department of Psychiatry and Behavioral Sciences, Emory University, Atlanta, GA, USA.

Abstract

Compounds 1-14 were synthesized in a search for high-affinity CRF1 receptor ligands that could be radiolabeled with (11)C or (18)F for use as positron emission tomography (PET) radiotracers. Derivatives of 2 were developed which contained amide N-fluoroalkyl substituents. Compounds [(18)F]24 and [(18)F]25 were found to have appropriate lipophilicities of logP7.4=2.2 but microPET imaging with [(18)F]25 demonstrated limited brain uptake.

KEYWORDS:

CRF-1 receptor; Corticotropin-releasing factor; Fluorine-18; PET imaging; Positron emission tomography

PMID:
26456805
PMCID:
PMC4628894
DOI:
10.1016/j.bmcl.2015.10.010
[Indexed for MEDLINE]
Free PMC Article

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