000836122 001__ 836122 000836122 005__ 20220930130127.0 000836122 0247_ $$2doi$$a10.1002/cmdc.201600592 000836122 0247_ $$2ISSN$$a1860-7179 000836122 0247_ $$2ISSN$$a1860-7187 000836122 0247_ $$2WOS$$aWOS:000403007000007 000836122 0247_ $$2Handle$$a2128/16691 000836122 0247_ $$2altmetric$$aaltmetric:19843323 000836122 0247_ $$2pmid$$apmid:28217962 000836122 037__ $$aFZJ-2017-05245 000836122 041__ $$aEnglish 000836122 082__ $$a540 000836122 1001_ $$0P:(DE-Juel1)131824$$aHolschbach, Marcus$$b0$$eCorresponding author$$ufzj 000836122 245__ $$aSynthesis and Pharmacological Evaluation of Identified and Putative Metabolites of the A 1 Adenosine Receptor Antagonist 8-Cyclopentyl-3-(3-fluoropropyl)-1-propylxanthine (CPFPX) 000836122 260__ $$aWeinheim [u.a.]$$bWiley-VCH$$c2017 000836122 3367_ $$2DRIVER$$aarticle 000836122 3367_ $$2DataCite$$aOutput Types/Journal article 000836122 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1516720369_21766 000836122 3367_ $$2BibTeX$$aARTICLE 000836122 3367_ $$2ORCID$$aJOURNAL_ARTICLE 000836122 3367_ $$00$$2EndNote$$aJournal Article 000836122 520__ $$aThe 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. 000836122 536__ $$0G:(DE-HGF)POF3-573$$a573 - Neuroimaging (POF3-573)$$cPOF3-573$$fPOF III$$x0 000836122 588__ $$aDataset connected to CrossRef 000836122 7001_ $$0P:(DE-Juel1)131810$$aBier, Dirk$$b1$$ufzj 000836122 7001_ $$0P:(DE-HGF)0$$aSihver, Wiebke$$b2 000836122 7001_ $$0P:(DE-Juel1)131847$$aSchulze, Annette$$b3$$ufzj 000836122 7001_ $$0P:(DE-Juel1)166419$$aNeumaier, Bernd$$b4$$ufzj 000836122 773__ $$0PERI:(DE-600)2209649-8$$a10.1002/cmdc.201600592$$gVol. 12, no. 10, p. 770 - 784$$n10$$p770 - 784$$tChemMedChem$$v12$$x1860-7179$$y2017 000836122 8564_ $$uhttps://juser.fz-juelich.de/record/836122/files/XanthinMetabolite_30_peerreviewed.pdf$$yPublished on 2017-05-22. Available in OpenAccess from 2018-05-22.$$zStatID:(DE-HGF)0510 000836122 8564_ $$uhttps://juser.fz-juelich.de/record/836122/files/XanthinMetabolite_30_peerreviewed.gif?subformat=icon$$xicon$$yPublished on 2017-05-22. Available in OpenAccess from 2018-05-22.$$zStatID:(DE-HGF)0510 000836122 8564_ $$uhttps://juser.fz-juelich.de/record/836122/files/XanthinMetabolite_30_peerreviewed.jpg?subformat=icon-1440$$xicon-1440$$yPublished on 2017-05-22. Available in OpenAccess from 2018-05-22.$$zStatID:(DE-HGF)0510 000836122 8564_ $$uhttps://juser.fz-juelich.de/record/836122/files/XanthinMetabolite_30_peerreviewed.jpg?subformat=icon-180$$xicon-180$$yPublished on 2017-05-22. Available in OpenAccess from 2018-05-22.$$zStatID:(DE-HGF)0510 000836122 8564_ $$uhttps://juser.fz-juelich.de/record/836122/files/XanthinMetabolite_30_peerreviewed.jpg?subformat=icon-640$$xicon-640$$yPublished on 2017-05-22. 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