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 H-3 receptor.

The synthesis of N-(cis-4-fluoromethylcyclohexyl)-4-(1(H)-imidazol-4-yl)pip eridine-1-thiocarbonamide (VUF 5000) 3, a fluorinated analogue of the poten t (pA(2) value of 8.9 +/- 0.1, K-i = 4.3 +/- 0.9 nM) histamine H-3 receptor antagonist thioperamide 2 is described. After the establishment of the H-3 antagonistic activity of VUF 5000, pA(2) value = 9.0 +/- 0.2, K-i = 2.3 +/ - 0.5 nM, a four step synthesis for the radiolabelling of VUF 5000 with F-1 8 (half life 110 min) was developed. Within 4 hours of the end of the bomba rtment, [F-18]VUF 5000 was obtained with an average radiochemical yield of 23% (decay corrected) acid a specific activity > 96.2 TBq/mu mol (2.6 Ci/mu mol).