Journal Article

FZJ-2017-05245

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Synthesis and Pharmacological Evaluation of Identified and Putative Metabolites of the A 1 Adenosine Receptor Antagonist 8-Cyclopentyl-3-(3-fluoropropyl)-1-propylxanthine (CPFPX)

Holschbach, M. (Corresponding author)FZJ* ; Bier, D.FZJ* ; Sihver, W. ; Schulze, A.FZJ* ; Neumaier, B.FZJ*

2017
Wiley-VCH Weinheim [u.a.]

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Please use a persistent id in citations: http://hdl.handle.net/2128/16691  doi:10.1002/cmdc.201600592

Abstract: The A1 adenosine receptor (A1AR) antagonist [18F]8-cyclopentyl-3-(3-fluoropropyl)-1-propylxanthine ([18F]CPFPX), used in imaging human brain A1ARs by positron emission tomography (PET), is stable in the brain, but rapidly undergoes transformation into one major (3-(3-fluoropropyl)-8-(3-oxocyclopenten-1-yl)-1-propylxanthine, M1) and several minor metabolites in blood. This report describes the synthesis of putative metabolites of CPFPX as standards for the identification of those metabolites. Analysis by (radio)HPLC revealed that extracts of human liver microsomes incubated with no-carrier-added (n.c.a.)[18F]CPFPX contain the major metabolite, M1, as well as radioactive metabolites corresponding to derivatives functionalized at the cyclopentyl moiety, but no N1-despropyl species or metabolites resulting from functionalization of the N3-fluoropropyl chain. The putative metabolites were found to displace the binding of [3H]CPFPX to the A1AR in pig brain cortex at Ki values between 1.9 and 380 nm and the binding of [3H]ZM241385 to the A2AAR in pig striatum at Ki values >180 nm. One metabolite, a derivative functionalized at the ω-position of the N1-propyl chain, showed high affinity (Ki 2 nm) to and very good selectivity (>9000) for the A1AR.

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Contributing Institute(s):

1. Nuklearchemie (INM-5)

Research Program(s):

1. 573 - Neuroimaging (POF3-573) (POF3-573)

Appears in the scientific report 2017

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Database coverage:
; ; BIOSIS Previews ; Current Contents - Life Sciences ; IF < 5 ; JCR ; NCBI Molecular Biology Database ; SCOPUS ; Science Citation Index ; Science Citation Index Expanded ; Thomson Reuters Master Journal List ; Web of Science Core Collection

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