Synthesis and utilization of 17-methyl and 17-cyclopropylmethyl-3, 14- dihydroxy-4,5-epoxy 6-fluoromorphinans (foxy and cyclofoxy) as (18F)-labeled opioid ligands for position emission transaxial tomography (PETT)

摘要

Fluorinated derivatives 3,14-dihydroxy-4,5-epoxy-6- fluoro- 17-methylmorphinan ("fluorooxymorphone"; FOXY, compound 10) and 17- cyclopropylmethyl-3,14-dihydroxy-4,5-epoxy-6-fluoromorphina n (CYCLOFOXY, compound 18) are prepared based upon the structures of the potent opioid agonist oxymorphone 4 and the antagonist naltrexone 11, respectively. Fluorine was introduced in the final stages of synthesis by a facile nucleophilic displacement with fluoride ion of the 6- triflate functions in 8 and 16. The synthetic procedures were suitable for the production of the corresponding positron emitting .sup.18 F- labeled analogs .sup.18 F-FOXY and .sup.18 F-CYCLOFOXY, which are useful for in vivo studies of the opioid receptor system using positron emission transaxial tomography. In addition, the tritiation of FOXY (10) to high specific activity is noted.