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Novel 6?-acylaminomorphinans with analgesic activity.


ABSTRACT: Aminomorphinans are a relatively young class of opioid drugs among which substances of high in vitro efficacy and favorable in vivo action are found. We report the synthesis and pharmacological evaluation of novel 6?-acylaminomorphinans. 6?-Morphinamine and 6?-codeinamine were stereoselectively synthesized by Mitsunobu reaction. The aminomorphinans were subsequently acylated with diversely substituted cinnamic acids. In vitro binding studies on cinnamoyl morphinamines showed moderate affinity for all opiate receptors with some selectivity for mu opioid receptors, while cinnamoyl codeinamines only showed affinity for mu opioid receptors. In vivo analgesia studies showed significant analgesic activity of 6?-cinnamoylmorphinamine mediated by mu and delta receptors. The lead compound was found to be roughly equipotent to morphine (ED?? 3.13 ± 1.09 mg/kg) but devoid of the dangerous side-effect respiratory depression, a major issue associated with traditional opioid therapy.

SUBMITTER: Varadi A 

PROVIDER: S-EPMC3839676 | biostudies-literature | 2013 Nov

REPOSITORIES: biostudies-literature

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Novel 6β-acylaminomorphinans with analgesic activity.

Váradi András A   Hosztafi Sándor S   Le Rouzic Valerie V   Tóth Gergő G   Urai Ákos Á   Noszál Béla B   Pasternak Gavril W GW   Grinnell Steven G SG   Majumdar Susruta S  

European journal of medicinal chemistry 20130922


Aminomorphinans are a relatively young class of opioid drugs among which substances of high in vitro efficacy and favorable in vivo action are found. We report the synthesis and pharmacological evaluation of novel 6β-acylaminomorphinans. 6β-Morphinamine and 6β-codeinamine were stereoselectively synthesized by Mitsunobu reaction. The aminomorphinans were subsequently acylated with diversely substituted cinnamic acids. In vitro binding studies on cinnamoyl morphinamines showed moderate affinity fo  ...[more]

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