Synthesis and biodistribution of [11C]R107474, a new radiolabeled alpha2-adrenoceptor antagonist

Bioorganic & Medicinal Chemistry
M Van der MeyJ E Leysen

Abstract

R107474, 2-methyl-3-[2-(1,2,3,4-tetrahydrobenzo[4,5]furo[3,2-c]pyridin-2-yl)ethyl]-4H-pyrido[1,2-a]pyrimidin-4-one, was investigated using in vitro and in vivo receptor assays and proved to be a potent and relatively selective alpha(2)-adrenoceptor antagonist. Performed assays in vitro were inhibition of binding to a large number of neurotransmitter receptor sites, drug receptor binding sites, ion channel binding sites, peptide receptor binding sites, and the monoamine transporters in membrane preparations of brain tissue or of cells expressing the cloned human receptors. The compound has subnanomolar affinity for halpha(2A)- and halpha(2C)-adrenoceptors (K(i) = 0.13 and 0.15 nM, respectively) and showed nanomolar affinity for the halpha(2B)-adrenoceptors and 5-hydroxytryptamine(7) (h5-HT(7)) receptors (K(i) = 1 and 5 nM, respectively). R107474 interacted weakly (K(i) values ranging between 81 and 920 nM) with dopamine-hD(2L), -hD(3) and -hD(4), h5-HT(1D)-, h5-HT(1F)-, h5-HT(2A)-, h5-HT(2C)-, and h5-HT(5A) receptors. The compound, tested up to 10 microM, interacted only at micromolar concentrations or not at all with any of the other receptor or transporter binding sites tested in this study. In vivo alpha(2A)- and alpha(2C)-ad...Continue Reading

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Citations

Apr 30, 2015·Psychopharmacology·Sjoerd J FinnemaSarah Grimwood
Dec 19, 2014·The International Journal of Neuropsychopharmacology·Sjoerd J FinnemaChrister Halldin
Feb 24, 2018·Angewandte Chemie·Yu-Feng LiangLutz Ackermann
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Sep 10, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Santosh Reddy AlluriKun-Eek Kil
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