Over the past 15 years, there has been a steady increase in the number of deaths in the United States from opioid drug overdose. Specifically, the number of deaths attributed to heroin overdose has risen from 2,000 deaths in 2002 to nearly 13,000 deaths in 2015. A combination of the increased availability of prescription opioid painkillers, the increase in Mexican and South American heroin production and the arrival of illicit fentanyl and analogues has led to a major public health crisis. Because opioid based analgesics still play an important role in the management of chronic or severe pain, the need to find a new analgesic with fewer negative side-effects and to find alternative treatment agents to ameliorate addictive diseases have become critical goals. Previous work in our group has identified 9β-hydroxy-<i>N-</i>phenethyl-5-phenylmorphan as the compound with the highest affinity to date for the mu-opioid receptor (MOR) in the 5-phenylmorphan series. We believe that the 8-hydroxyphenylmorphan (PM) derivatives will show similar affinity for both the MOR and delta-opioid receptor (DOR). It is hoped, with some expectation of success from previous studies on a related substrate, that some of these new compounds will act as MOR agonists and DOR antagonists, the combination of interactions that has been said to produce analgesics with fewer side-effects, without tolerance and dependence, and perhaps a different type of treatment agent. The synthesis and chiral resolution of the PM derivatives is presented in the poster.

Synthesis and chiral resolution of <i>N</i>-substituted 8-hydroxyphenylmorphans: Potential ligands for the Mu and delta opioid receptors

254th National Meeting (2017)

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Synthesis and chiral resolution of N-substituted 8-hydroxyphenylmorphans: Potential ligands for the Mu and delta opioid receptors