Metazocine

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Metazocine
Metazocine.png
Systematic (IUPAC) name
(2R,6R,11R)-3,6,11-trimethyl-1,2,3,4,5,6-hexahydro-2,6-methanobenzo[d]azocin-8-ol
Clinical data
  • US 2
?
Identifiers
3734-52-9 N
None
PubChem CID 62518
ChemSpider 56292 YesY
UNII XD53YGT34W YesY
ChEMBL CHEMBL257661 N
Chemical data
Formula C15H21NO
231.333 g/mol
 N (what is this?)  (verify)

Metazocine is an opioid analgesic related to pentazocine. While metazocine has significant analgesic effects,[1] mediated through a mixed agonist–antagonist action[2] at the mu opioid receptor,[3] its clinical use is limited by dysphoric and hallucinogenic effects which are most likely caused by activity at kappa opioid receptors (where it is a high-efficacy agonist)[4] and/or sigma receptors.[5][6]

Syntheses[edit]

The prototype benzomorphan, metazocine (5), can be obtained from a variation of the morphinan synthesis.

Metazocine synthesis:[7][8]

Thus, Rxn of the Grignard reagent from p-methoxybenzyl chloride (1) with the lutidine methiodide (2) affords the benzylated dihydropyridine (3). (The addition to the most hindered position is rather puzzling.) Reduction of the enamine π-bond leads to the tetrahydropyridine (4). Cyclization by means of acid leads directly to the benzomorphan ring system (5). Demethylation of the aromatic ring system affords the phenol. Although this last compound is in fact a relatively potent analgesic, it is not available commercially as a drug.

See also[edit]

References[edit]

  1. ^ Hori M, Ban M, Imai E, Iwata N, Suzuki Y, Baba Y, Morita T, Fujimura H, Nozaki M, Niwa M. Novel nonnarcotic analgesics with an improved therapeutic ratio. Structure-activity relationships of 8-(methylthio)- and 8-(acylthio)-1,2,3,4,5,6-hexahydro-2,6-methano-3-benzazocines. Journal of Medicinal Chemistry. 1985 Nov;28(11):1656-61.
  2. ^ Berzetei-Gurske I, Loew GH. The novel antagonist profile of (-)metazocine. Progress in Clinical and Biological Research. 1990;328:33-6.
  3. ^ Gharagozlou P, Demirci H, David Clark J, Lameh J. Activity of opioid ligands in cells expressing cloned mu opioid receptors. BMC Pharmacology. 2003 Jan 4;3:1.
  4. ^ Gharagozlou P, Hashemi E, DeLorey TM, Clark JD, Lameh J. Pharmacological profiles of opioid ligands at kappa opioid receptors. BMC Pharmacology. 2006 Jan 25;6:3.
  5. ^ Shannon HE. Pharmacological analysis of the phencyclidine-like discriminative stimulus properties of narcotic derivatives in rats. Journal of Pharmacology and Experimental Therapeutics. 1982 Jul;222(1):146-51.
  6. ^ Slifer BL, Balster RL, May EL. Reinforcing and phencyclidine-like stimulus properties of enantiomers of metazocine. Pharmacology, Biochemistry and Behaviour. 1986 Oct;25(4):785-9.
  7. ^ May, E. L.; Fry, E. M. (1957). "Structures Related to Morphine. VIII. Further Syntheses in the Benzomorphan Series*1,2". The Journal of Organic Chemistry 22 (11): 1366. doi:10.1021/jo01362a017.  edit
  8. ^ May, E. L.; Ager, J. H. (1959). "Structures Related to Morphine. XI.1Analogs and a Diastereoisomer of 2'-Hydroxy-2,5,9-trimethyl-6,7-benzomorphan". The Journal of Organic Chemistry 24 (10): 1432. doi:10.1021/jo01092a011.  edit