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Synthesis, Pharmacology, and Molecular Docking Studies on 6-Desoxo-N-methylmorphinans as Potent ?-Opioid Receptor Agonists.

ABSTRACT: Position 6 of the morphinan skeleton plays a key role in the ?-opioid receptor (MOR) activity in vitro and in vivo. We describe the consequence of the 6-carbonyl group deletion in N-methylmorphinan-6-ones 1-4 on ligand-MOR interaction, signaling, and antinociception. While 6-desoxo compounds 1a, 2a, and 4a show similar profiles to their 6-keto counterparts, the 6-desoxo-14-benzyloxy substituted 3a displays significantly increased MOR binding and agonist potency and a distinct binding mode compared with its analogue 3.

SUBMITTER: Dumitrascuta M

PROVIDER: S-EPMC5706069 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

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Synthesis, Pharmacology, and Molecular Docking Studies on 6-Desoxo-N-methylmorphinans as Potent μ-Opioid Receptor Agonists.

Dumitrascuta Maria M Ben Haddou Tanila T Guerrieri Elena E Noha Stefan M SM Schläfer Lea L Schmidhammer Helmut H Spetea Mariana M

Journal of medicinal chemistry 20171103 22

Position 6 of the morphinan skeleton plays a key role in the μ-opioid receptor (MOR) activity in vitro and in vivo. We describe the consequence of the 6-carbonyl group deletion in N-methylmorphinan-6-ones 1-4 on ligand-MOR interaction, signaling, and antinociception. While 6-desoxo compounds 1a, 2a, and 4a show similar profiles to their 6-keto counterparts, the 6-desoxo-14-benzyloxy substituted 3a displays significantly increased MOR binding and agonist potency and a distinct binding mode compar ...[more]

PMID: 29053268

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