SYNTHESIS AND OPIOID ACTIVITIES OF SOME NALTREXONE OXIME ETHERS

A series of alkyl, cycloalkyl, aryl, and aralkyl ethers of naltrexone oxime was prepared. The compounds were examined in binding assays for mu, delta and kappa opioid receptor affinity. In addition, the naltrex one oxime ethers were studied in animal models that measure opioid ago nist and antagonist activity. These studies led to the discovery of se veral compounds, notably phenethyl 3e and phenylpropyl 3f ethers of na ltrexone, which have a 10-fold increase in potency at the kappa opioid receptor with potent mu and kappa agonist properties in vivo.