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

摘要

Fluorinated derivatives 3,14-dihydroxy-4,5 alpha -epoxy-6 beta -fluoro-17-methylmorphinan ("fluorooxymorphone"; FOXY, compound 10) and 17-cyclopropylmethyl-3,14-dihydroxy-4,5 alpha -epoxy-6 beta -fluoromorphinan (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 alpha -triflate functions in 8 and 16. The synthetic procedures were suitable for the production of the corresponding positron emitting 18F-labeled analogs 18F-FOXY and 18F-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.