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

Article abstract of DOI:10.1002/(SICI)1099-1344(199903)42:3<293::AID-JLCR191>3.0.CO;2-B

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).