Oxymorphone analogue

It is N-allyl analogue of oxymorphone, have a high affinity for mu receptor and lower affinity at delta and kappa sites. It selectively antagonizes the respiratory depression produced by opioids. After intravenous administration, it antagonizes all actions of morphine. It also blocks the actions of endogenous opioid peptides. 

Catalytic hydrogenation of the hydrolysis product leads to the orally active compound oxycodenone (7-1), which is used in a number of analgesic drugs. Cleavage of the methyl ether to the free phenol leads to one of the most potent close analogues of morphine, oxymorphone (7-2) [5]. Note that both of these compounds carry the hazards of classical opiate dependence liability. 

Naltrexone and nalmefene are structurally related to naloxone. Naltrexone is the /V-cyclopropy I methyl analogue of oxymorphone while nalmefene is the /V-allyl analogue. They have similar pharmacological properties to naloxone but with longer durations of action, with elimination half-lives in excess of 8 hours. They also have significant oral availability. They are used mainly in the management of addicts. 

EN 1639A UM 792 Nalorex " Trexan ) is one of the phenanthrene series and an analogue of oxymorphone and thebaine, and is also an analogue of the antagonist naloxone. It is a (largely subtype-unselective) opioid RECEPTOR antagonist, and is used orally in detoxification treatment for formerly opioid-dependent individuals to help prevent relapse. 

The 17 - N- a 11 y I - (n a I o x o n e. 3a) and 17 - /V-c v c lop I opv I m e t h v I (naltrexone, 3b) analogues of oxymorphone (2d) are the prototype opioid receptor antagonists with some selectivity for MOR. They have entered clinical practice as treatments for narcotic overdose (naloxone) and alcoholism or opioid abuse/dependence (naltrexone). The 17-quatemary derivative of naltrexone, methylnaltrexone (4) has recently been introduced into clinical practice as a treatment for opiate-induced bowel dysfunction [1],... 

Recently a great deal of attention has been focused on the oxymorphone series (III) of morphine derivatives with an axial OH substituent on the C14 position of hydro-morphone. One reason for this interest is that the N-allyl derivative in this series, naloxone (IIIB) has been found to be a pure antagonist, much more potent than its morphine analogue, nalorphine (IB) and with more morphine-like, rather than nalorphine-like side effects and low addiction capacity. The addition of an OH group on Cl4 also causes an apparent two-fold increase in potency from hydromorphone to oxymorphone. Similarly, a six-fold increase in apparent analgesic potency is observed in going from hydrocodone (IIB) to oxycodone (IIIC) [1]. 

---