Synthesis, in vitro pharmacology and radiosynthesis of N-(cis-4-fluoromethylcyclohexyl)-4-(1(H)-imidazol-4-yl)piperidine-1 -thiocarbonamide (VUF 5000), a potential pet ligand for the histamine H3 receptor

Albert D. Windhorst*, Henk Timmerman, Wiro M P B Menge, Rob Leurs, Jacobus D M Herscheid

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

The synthesis of N-(cis-4-fluoromethylcyclohexyl)-4-(1(H)-imidazol-4-yl)piperidine-1 -thiocarbonamide (VUF 5000) 3, a fluorinated analogue of the potent (pA2 value of 8.9 ± 0.1, K(i) = 4.3 ± 0.9 nM) histamine H3 receptor antagonist thioperamide 2 is described. After the establishment of the H3 antagonistic activity of VUF 5000, pA2 value = 9.0 ± 0.2, K(i) = 2.3 ± 0.5 nM, a four step synthesis for the radiolabelling of VUF 5000 with 18F (half life 110 min) was developed. Within 4 hours of the end of the bombartment, [18F]VUF 5000 was obtained with an average radiochemical yield of 23% (decay corrected) and a specific activity > 96.2 TBq/μmol (2.6 Ci/μmol).

Original languageEnglish
Pages (from-to)293-307
Number of pages15
JournalJournal of Labelled Compounds and Radiopharmaceuticals
Volume42
Issue number3
DOIs
Publication statusPublished - 1 Jan 1999

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