14-amino-4,5-epoxymorphinan derivatives and their pharmacological actions

Abstract

14-Hydroxy-7,8-dihydromorphinone (oxymorphone) and its derivatives (oxycodone, naloxone, naltrexone) have become among the most important clinical agents to have been produced from opium. 14-Aminocodeinone and its 7,8-dihydro and morphinone derivatives are of more recent origin thanks to the work of Professor Gordon Kirby and his collaborators. The 14-amino parent compounds have proved of limited interest but their 14-acylamino- and 14-alkylamino derivatives have been extensively studied. The 4′ -substituted cinnamoylamino-17-cyclopropylmethyl-7,8-dihydronormorphinones, C-CAM and M-CAM are the best available selective MOR irreversible antagonists and the related dihydrocodeinone MC-CAM, 4′-chlorocinnamoylamino-17-cyclopropylmethyl-7,8- dihydronorcodeinone, is a long-acting MOR partial agonist with extended MOR-pseudoirreversible antagonist activity that could be a candidate for pharmacotherapy of opiate abuse/dependence. © 2010 Springer-Verlag Berlin Heidelberg.