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)

US4775759A · kind A · utility

Assignee

• The United States of America, as represented by the Department of Health and Human Services · US

Inventors

• Kenner C. Rice · Bethesda, US
• Candace B. Pert · Potomac, US
• Terrence R. Burke, Jr. · Kirkwood, US
• Steven M. Larson · New York, US
• William C. Eckelman · Rockville, US
• Michael A. Channing · Annapolis, US

Key dates

• Filing date: Nov 27, 1984
• Grant date: Oct 4, 1988
• Expiry date: Nov 27, 2004

Classification

• Technology area (CPC A): Human Necessities
• CPC primary: A61K2123/00
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

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.-fluoromorphin an (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 .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.