N-Phenethylnormorphine Explained

N-Phenethylnormorphine is an opioid analgesic drug derived from morphine by replacing the N-methyl group with β-phenethyl.^[1] It is around eight to fourteen times more potent than morphine as a result of this modification,^[2] in contrast to most other N-substituted derivatives of morphine, which are substantially less active, or act as antagonists.^[3] Binding studies have helped to explain the increased potency of N-phenethylnormorphine, showing that the phenethyl group extends out to reach an additional binding point deeper inside the μ-opioid receptor cleft, analogous to the binding of the phenethyl group on fentanyl.^{[4] [5]}

See also

• 14-Cinnamoyloxycodeinone
• 14-Phenylpropoxymetopon
• 7-PET
• MR-2096
• N-Phenethyl-14-ethoxymetopon
• N-Phenethylnordesomorphine
• Phenomorphan
• RAM-378
• Ro4-1539

Notes and References

1. Small L, Eddy N, Ager J, May E . 1958 . Notes: An Improved Synthesis of N-Phenethylnormorphine and Analogs . Journal of Organic Chemistry . 23 . 9 . 1387–1388 . 10.1021/jo01103a615 .
2. Eddy NB . The search for new analgesics . Journal of Chronic Diseases . 4 . 1 . 59–71 . July 1956 . 13332043 . 10.1016/0021-9681(56)90007-8 .
3. DeGraw JI, Lawson JA, Crase JL, Johnson HL, Ellis M, Uyeno ET, Loew GH, Berkowitz DS . 6 . Analgesics. 1. Synthesis and analgesic properties of N-sec-alkyl- and N-tert-alkylnormorphines . Journal of Medicinal Chemistry . 21 . 5 . 415–22 . May 1978 . 207868 . 10.1021/jm00203a002 .
4. Subramanian G, Paterlini MG, Portoghese PS, Ferguson DM . Molecular docking reveals a novel binding site model for fentanyl at the mu-opioid receptor . Journal of Medicinal Chemistry . 43 . 3 . 381–91 . February 2000 . 10669565 . 10.1021/jm9903702 .
5. Book: McFadyen I, Metzger T, Subramanian G, Poda G, Jorvig E, Ferguson DM . Molecular modeling of opioid receptor-ligand complexes . 40 . 107–35 . 2002 . 12516524 . 10.1016/S0079-6468(08)70083-3 . 9780444510549 . Progress in Medicinal Chemistry .