Effect of a 6-cyano substituent in 14-oxygenated N-methylmorphinans on opioid receptor binding and antinociceptive potency

Journal of Medicinal Chemistry

Volumn 48, Issue 15, 2005, Pages 5052-5055

  Spetea, Mariana ^a,b   Greiner, Elisabeth ^a   Aceto, Mario D ^c   Harris, Louis S ^c   Coop, Andrew ^d   Schmidhammer, Helmut ^a  

^a UNIVERSITY OF INNSBRUCK   (Austria)

^b INNSBRUCK MEDICAL UNIVERSITY   (Austria)

^c VIRGINIA COMMONWEALTH UNIVERSITY SCHOOL OF MEDICINE   (United States)

^d UNIVERSITY OF MARYLAND SCHOOL OF PHARMACY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

14 HYDROXY 6 CYANOMORPHINAN; 14 HYDROXY 6 KETOMORPHINAN; 5,6 DIDEHYDRO 14BETA HYDROXY 3,4 DIMETHOXY 17 METHYLMORPHINAN 6 CARBONITRILE; ANTINOCICEPTIVE AGENT; BRIDGED COMPOUND; DELTA OPIATE RECEPTOR; DELTORPHIN; ENKEPHALIN[2 DEXTRO ALANINE 4 METHYLPHENYLALANINE 5 GLYCINE]; KAPPA OPIATE RECEPTOR; KETONE DERIVATIVE; METHYL GROUP; MORPHINAN DERIVATIVE; MORPHINE; MU OPIATE RECEPTOR; N METHYL N [7 (1 PYRROLIDINYL) 1 OXASPIRO[4.5]DEC 8 YL]BENZENEACETAMIDE; NITRILE; OXYCODONE; OXYGEN DERIVATIVE; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANTINOCICEPTION; ARTICLE; BINDING AFFINITY; CONTROLLED STUDY; DRUG POTENCY; DRUG RECEPTOR BINDING; DRUG SELECTIVITY; DRUG SYNTHESIS; HOT PLATE TEST; IN VIVO STUDY; MALE; MOUSE; NONHUMAN; RAT; STRUCTURE ACTIVITY RELATION; TAIL FLICK TEST; WRITHING TEST;

ANALGESICS; ANIMALS; BRAIN; MICE; MICE, INBRED ICR; MORPHINANS; NITRILES; RATS; RECEPTORS, OPIOID; RECEPTORS, OPIOID, DELTA; RECEPTORS, OPIOID, KAPPA; RECEPTORS, OPIOID, MU; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 22744454428     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm0580205     Document Type: Article

References (28)

1. Schmidhammer, H.; Aeppli, L.; Atwell, L.; Fritsch, F.; Jacobson, A. E.; Nebuchla, M.; Sperk, G. Synthesis and Biological Evaluation of 14-Alkoxymorphinans. 1. Highly Potent Opioid Agonists in the Series of (-)-14-Methoxy-N-methylmorphinan-6-ones. J. Med. Chem. 1984, 27, 1575-1579.
2. Spetea, M.; Schüllner, F.; Moisa, R. C.; Berzetei-Gurske, I. P.; Schraml, B.; Dörfler, C.; Aceto, M. D.; Harris, L. S.; Coop, A.; Schmidhammer H. Synthesis and Biological Evaluation of 14-Alkoxymorphinans. 21. Novel 4-Alkoxy and 14-Phenylpropoxy Derivatives of the μ Opioid Receptor Antagonist Cyprodime. J. Med. Chem. 2004, 47, 3242-3247.
3. Pasternak, G. W.; Hahn, E. F. Long-acting Opiate Agonists and Antagonists: 14-Hydroxydihydromorphinone Hydrazones. J. Med. Chem. 1980, 23, 674-676.
4. 3H]-Oxymorphazone to Rat Brain Membranes. Life Sci. 1987, 40, 1579-1588.
5. 3H]-Naloxone Binding Sites by C-6 Derivatives of Morphinan-6-ones. Life Sci. 1991, 48, 439-451.
6. Spetea, M.; Friedmann, T.; Riba, P.; Schütz, J.; Wunder, G.; Langer, T.; Schmidhammer, H.; Fürst S. In Vitro Opioid Activity Profiles of 6-Amino Acid Substituted Derivatives of 14-O-Methyloxymorphone. Eur. J. Pharmacol. 2004, 483, 301-308.
7. 3H] Binding Sites in Rat Brain. Pharm. Res. 1992, 25, 31-32.
8. Schmidhammer H. 14-Alkoxymorphinans - A Series of Highly Potent Opioid Agonists, Antagonists, and Partial Agonists. Curr. Topics Med. Chem. 1993, 1, 261-276.
9. Fürst, S.; Hosztafi, S.; Friedmann, T. Structure-Activity Relationships of Synthetic and Semisynthetic Opioid Agonists and Antagonists. Curr. Med. Chem. 1995, 1, 423-440.
10. Fürst, S.; Riba, P.; Friedmann, T.; Timar, J.; Al-Khrasani, M.; Obara, I.; Makuch, W.; Spetea, M.; Schütz, J.; Przewlocki, R.; Przewlocka, B.; Schmidhammer, H. Peripheral versus Central Antinociceptive Actions of 6-Amino Acid-substituted Derivatives of 14-O-Methyloxymorphone in Acute and Inflammatory Pain in the Rat. J. Pharmacol. Exp. Ther. 2005, 312, 609-618.
11. Greiner, E.; Schottenberger, H.; Wurst, K.; Schmidhammer, H. Novel Class of Morphinans with Acrylonitrile Incorporated Substructures as Key Intermediates for Non-oxygen-bridged Opioid Ligands. J. Am. Chem. Soc. 2001, 123, 3840-3841.
12. Seki, I.; Takagi, H.; Kobayashi, S. Pharmacological Studies on Morphine Derivatives. 3. On the Chemical Structure-Activity Relationships of 14-Hydroxymorphine Derivatives. Yakugaku Zasshi 1964, 84, 280-286.
13. Schmidhammer, H.; Jacobson, A. E.; Brossi, A. Chemical and Biological Study of Aromatic Oxygenated 6-Ketomorphinans. Med. Res. Rev. 1983, 3, 1-19.
14. Schmidhammer, H.; Jacobson, A. E.; Atwell, L.; Brossi, A. Structure-Activity Relationship of Oxygenated Morphinans. V. Narcotic Agonist and Antagonist Activity in the 14-Hydroxymorphinan Series. Helv. Chim. Acta 1981, 64, 2540-2543.
15. Kobylecki, R. J.; Carling, R. W.; Lord, J. A. H.; Smith, C. F. C.; Lane, A. C. Common Anionic Receptor Site Hypothesis: Its Relevance to the Action of Naloxone. J. Med. Chem. 1982, 25, 116-120.
16. Spetea, M.; Erlandsson Harris, H.; Berzetei-Gurske, I. P.; Klareskog, L.; Schmidhammer, H. Binding, Pharmacological and Immunological Profiles of the δ Selective Opioid Receptor Antagonist HS 378. Life Sci. 2001, 69, 1775-1782.
17. Schütz, J.; Spetea, M.; Koch, M.; Aceto, M. D.; Harris, L. S.; Coop, A.; Schmidhammer, H. Synthesis and Biological Evaluation of 14-Alkoxymorphinans. 20. 14-Phenylpropoxymetopon - an Extremely Powerful Analgesic. J. Med. Chem. 2003, 46, 4182-4187.
18. Schütz, J.; Brandt, W.; Spetea, M.; Wurst, K.; Wunder, G.; Schmidhammer, H. Synthesis of 6-Amino Acid Substituted Derivatives of the Highly Potent Analgesic 14-O-methyloxymorphone. Helv Chim. Acta 2003, 86, 2142-2148.
19. Abbott, F. V.; Palmour, R. M. Morphine-6-glucuronide: Analgesic Effects and Receptor Binding Profile in Rats. Life Sci. 1988, 43, 1685-1695.
20. Frances, B.; Gout, R.; Monsarrat, B., Cros, J.; Zajac, J. M. Further Evidence that Morphine-6β-glucuronide is a More Potent Opioid Agonist than Morphine. J. Pharmacol. Exp. Ther. 1992, 262, 25-31.
21. Botros, S.; Lipkowski, A. W.; Larson, D. L.; Stark, A. P.; Takemori, A. E.; Portoghese, P. S. Opioid Agonist and Antagonist Activities of Peripherally Selective Derivatives of Naltrexamine and Oxymorphamine. J. Med. Chem. 1989, 32, 2068-2071.
22. Eddy, N. B.; Leimbach, D. Synthetic Analgesics. II. Dithienylbutenylamines and Dithienylbutylamines. J. Pharmacol. Exp. Ther. 1953, 107, 385-393.
23. D'Amour, F. E.; Smith, D. L. A Method for Determining Loss of Pain Sensation. J. Pharmacol. Exp. Ther. 1941, 72, 74-79.
24. Dewey, W. L.; Harris, L. S. Antinociceptive Activity of the Narcotic Antagonist Analgesics and Antagonistic Activity of Narcotic Analgesics in Rodents. J. Pharmacol. Exp. Ther. 1971, 179, 652-659.
25. May, E. L.; Aceto, M. D.; Bowman, E. R.; Bentley, C.; Martin, B. R.; Harris, L. S.; Medzihradsky, F.; Mattson, M. V.; Jacobson, A. E. Antipodal α-N-(Methyl through Decyl)-N-normetazocines (5,9α-Dimethyl-2′- hydroxy-6,7-benzomorphans): In Vitro and in Vivo Properties. J. Med. Chem. 1994, 37, 3408-3418.
26. 3H]-14-Methoxymetopon, a High Affinity μ Opioid Receptor Agonist. Eur. J. Neurosci. 2003, 18, 290-295.
27. Aceto, M. D.; Bowman, E. R.; Harris, L. S.; Hughes, L. D.; Kipps, B. R.; May, E. L. Dependence Studies of New Compounds in the Rhesus Monkey, Rat, and Mouse. In Problems of Drug Dependence 2002; Proceedings of the 64th Annual Scientific Meeting of the College of Problems on Drug Dependence, National Institute on Drug Abuse Research Monograph Series, 2003, Vol. 183, pp 191-227.
28. Greiner, E.; Spetea, M.; Krassnig, R.; Schüllner, F.; Aceto, M.; Harris, L. S.; Traynor, J. R.; Woods, J. H.; Coop, A.; Schmidhammer, H. Synthesis and Biological Evaluation of 14-Alkoxymorphinans. 18. N-Substituted 14-Phenylpropyloxymorphinan-6-ones with Unanticipated Agonist Properties: Extending the Scope of Common Structure-Activity Relationships. J. Med. Chem. 2003, 46, 1758-1763.