Synthesis, Pharmacology, and Molecular Docking Studies on 6-Desoxo-N-methylmorphinans as Potent mu-Opioid Receptor Agonists.
Article Details
- CitationCopy to clipboard
Dumitrascuta M, Ben Haddou T, Guerrieri E, Noha SM, Schlafer L, Schmidhammer H, Spetea M
Synthesis, Pharmacology, and Molecular Docking Studies on 6-Desoxo-N-methylmorphinans as Potent mu-Opioid Receptor Agonists.
J Med Chem. 2017 Nov 22;60(22):9407-9412. doi: 10.1021/acs.jmedchem.7b01363. Epub 2017 Nov 3.
- PubMed ID
- 29053268 [ View in PubMed]
- Abstract
Position 6 of the morphinan skeleton plays a key role in the mu-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.