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Systematic (IUPAC) name
CAS Registry Number 69815-38-9
ATC code None
ChemSpider 21476727
Chemical data
Formula C19H25NO2
Molecular mass 299.41 g/mol

Proxorphan is an opioid analgesic and antitussive drug of the morphinan family that was never marketed.[1] It acts as a κ-opioid receptor partial agonist and to a lesser extent as a μ-opioid receptor partial agonist.[2][3][4][5]


T. A. Montzka, J. D. Matiskella and R. A. Partyka, U.S. Patent 4,246,413; Chem. Abstr. 95, 43442z (1981).

Starting material for this preparation is ketoester 1, available by one of the classical benzomorphan syntheses.[6] Condensation with the ylide from Triethyl phosphonoacetate (HWE reaction) affords diester 2. Catalytic hydrogenation proceeds from the less hindered face to afford the corresponding saturated diester (3). The esters are then reduced by means of LiAlH4 to give the glycol (4); this undergoes internal ether formation on treatment with acid to form the pyran ring of 5. Von Braun reaction with BrCN (or ethyl chloroformate) followed by saponification of the intermediate leads to the 2° amine (6). This is converted to the cyclopropylmethyl derivative 8 by acylation with cyclopropylcarbonyl chloride[7][8] followed by reduction of the thus formed amide (7) with LiAlH4. Cleave of the O-methyl ether with sodium Ethanethiol affords proxorphan (9).

See also[edit]


  1. ^ David J. Triggle (1997). Dictionary of pharmacological agents. London: Chapman & Hall. ISBN 0-412-46630-9. 
  2. ^ Leander JD (October 1983). "Further study of kappa opioids on increased urination". The Journal of Pharmacology and Experimental Therapeutics 227 (1): 35–41. PMID 6137557. 
  3. ^ Hayes AG, Birch PJ (August 1988). "Reversal by beta-funaltrexamine and 16-methyl cyprenorphine of the antinociceptive effects of opioid agonists in the mouse and guinea-pig". Neuropharmacology 27 (8): 813–6. doi:10.1016/0028-3908(88)90096-2. PMID 3216959. 
  4. ^ Picker MJ, Dykstra LA (May 1989). "Discriminative stimulus effects of mu and kappa opioids in the pigeon: analysis of the effects of full and partial mu and kappa agonists". The Journal of Pharmacology and Experimental Therapeutics 249 (2): 557–66. PMID 2566680. 
  5. ^ Picker MJ, Craft RM, Negus SS, et al. (November 1992). "Intermediate efficacy mu opioids: examination of their morphine-like stimulus effects and response rate-decreasing effects in morphine-tolerant rats". The Journal of Pharmacology and Experimental Therapeutics 263 (2): 668–81. PMID 1331411. 
  6. ^ doi:10.1039/JR9470000399
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  7. ^
  8. ^ U.S. Patent 5,504,245