N-Phenethylnormorphine is an
opioidanalgesic 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]
^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.
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10.1021/jo01103a615.
^DeGraw JI, Lawson JA, Crase JL, Johnson HL, Ellis M, Uyeno ET, et al. (May 1978). "Analgesics. 1. Synthesis and analgesic properties of N-sec-alkyl- and N-tert-alkylnormorphines". Journal of Medicinal Chemistry. 21 (5): 415–22.
doi:
10.1021/jm00203a002.
PMID207868.
^Subramanian G, Paterlini MG, Portoghese PS, Ferguson DM (February 2000). "Molecular docking reveals a novel binding site model for fentanyl at the mu-opioid receptor". Journal of Medicinal Chemistry. 43 (3): 381–91.
doi:
10.1021/jm9903702.
PMID10669565.
^McFadyen I, Metzger T, Subramanian G, Poda G, Jorvig E, Ferguson DM (2002). Molecular modeling of opioid receptor-ligand complexes. Progress in Medicinal Chemistry. Vol. 40. pp. 107–35.
doi:
10.1016/S0079-6468(08)70083-3.
ISBN9780444510549.
PMID12516524.