10-ketonaltrexone and 10-ketooxymorphone

Article abstract of DOI:10.1021/jm00145a024

Ethylketocyclazocine has greater κ/μ selectivity than cyclazocine in brain binding assays. 10-Ketonaltrexone (11) and 10-ketooxymorphone (10) were prepared from naltrexone 3-methyl ether and oxycodone, respectively. Bioassays in the myenteric plexus longitudinal muscle preparation of the guinea pig ileum and in the mouse vas deferens, in addition to brain binding assays, demonstrated that 10 and 11 were far less potent than naltrexone and oxymorphone at μ sites and also had little affinity for κ and δ sites. It is concluded that introduction of the 10-keto group in naltrexone and oxymorphone diminished opioid effects at all binding sites.