Introduction of a 6-cyano group in 14-oxygenated N-methylmorphinans influences in vitro and in vivo pharmacological activities

Abstract

Background Being a disabling symptom of many medical conditions, effective pain control is one of the most important therapeutic priorities. Morphine and other opioid drugs produce analgesia primarily through μ opioid (MOP) receptors, which mediate beneficial but also the nonbeneficial actions. Appropriate identification of novel opioid analgesics may reduce complications and improve patient compliance. It was reported that hydrazones, oximes, carbazones and semicarbazone derivatives of morphinan-6-ones, e.g. dihydromorphinone or oxymorphone, exhibit high affinity at the MOP receptor [1]. Since most of these structures show high antinociceptive potency while having less pronounced side effects, it remains a promising task to convert the carbonyl group of morphinan-6-ones into various functionalities. In this study, we aimed to investigate the effect of the replacement of the 6-keto function with a 6-cyano group on in vitro and in vivo pharmacological profiles.