Among
opioids,
morphinans play an important role as therapeutically valuable drugs. They include
pain relieving agents such as naturally occurring
alkaloids (e.g.
morphine,
codeine), semisynthetic derivatives (e.g.
oxycodone,
oxymorphone,
buprenorphine), and synthetic analogs (e.g.
levorphanol). Currently used
opioid analgesics also share a number of severe side effects, limiting their clinical usefulness. The antagonist
morphinans,
naloxone and
naltrexone are used to treat
opioid overdose,
opioid dependence, and
alcoholism. All these
opioid drugs produce their biological actions through three receptor types, mu, delta, and kappa, belonging to the
G-protein-coupled receptor family. Considerable effort has been put forward to understand the appropriate use of
opioid analgesics, while medicinal chemistry and
opioid pharmacology have been continuously engaged in the search for safer, more efficacious and nonaddicting
opioid compounds, with the final goal to reduce complications and to improve patient compliance. Toward this goal, recent advances in chemistry,
ligand-based structure activity relationships and pharmacology of 14-alkoxymorphinans are reviewed in this chapter. Current developments of different structural patterns of 14-alkoxymorphinans as research tools and their potential therapeutic opportunities are also summarized.