Skip to main content
SpringerLink
Log in

Miscellaneous Groups of Analgesics

  • Chapter
Opioid Analgesics

Abstract

Up to the late 1950s the goal of potency in the development of novel analgesics was that of the classic opiate morphine. However, in 1957 it was made apparent from reports from CIBA on analgesics based on benzimidazole that levels of activity several orders above this standard could be achieved, and the group is of historical importance on this account.(1,2) The compounds of general formula 3 carry a 2-aminoethyl substituent at N-1 and a benzyl substituent at C-2 with further substituents at C-5 and C-4′ in the more potent derivatives. Two synthetic routes were employed (Scheme 11.1)(3): (a) condense

Seheme 11.1

substituted o-phenylenediamines with a substituted benzyl cyanide (or related compound) and alkylate the product with a 2-t-aminoethyl chloride (1–3), and (b) (appropriate to derivatives with R′ substituents) condense 1-amino-2-diethylaminoethane with a 2-nitrochlorobenzene, reduce the nitro group with (NH4)2S (a 5-NO2 substituent is unchanged), and condense the product 2 with an iminoether formed from a benzyl cyanide and EtOH-HCl.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 299.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. A. Hunger, J. Kebrle, A. Rossi, and K. Hoffmann, Experientia 13, 400 (1957).

    Article  PubMed  CAS  Google Scholar 

  2. F. Gross and H. Tuman, Experientia 13, 401 (1957).

    Article  PubMed  CAS  Google Scholar 

  3. A. Hunger, J. Kebrle, A. Rossi, and K. Hoffmann, Heh. Chim. Acta 43, 800, 1032, 1046, 1298, 1727 (1960).

    Google Scholar 

  4. N. B. Eddy, Chem. Ind. (Lond.) 1462 (1959).

    Google Scholar 

  5. G. Bromig, Klin. Wschr. 36, 960 (1958).

    Article  PubMed  CAS  Google Scholar 

  6. G. A. Deneau, J. McCarthy and M. H. Seevers, Minutes 20th Meeting Committee on Drug Addiction and Narcotics, National Research Council, Washington, D. C., January 1959, Addendum 1.

    Google Scholar 

  7. H. F. Fraser, H. Isbell and A. B. Wolbach, 21st Meeting Committee on Drug Addiction and Narcotics, National Research Council, Washington, D. C., January 1960, Addendum 2, p. 35.

    Google Scholar 

  8. A. Wikler, private communication.

    Google Scholar 

  9. A. F. Casy and J. Wright, J. Chem. Soc. (C) 1167 (1966).

    Google Scholar 

  10. A. F. Casy and J. Wright, J. Pharm. Pharmacol. 18, 677 (1966).

    Article  PubMed  CAS  Google Scholar 

  11. A. Hunger, J. Kebrle, A. Rossi, and K. Hoffmann, Helv. Chim. Acta 44, 1273 (1961).

    Article  CAS  Google Scholar 

  12. F. N. Marshall, W. R. Jones, and L. C. Weaver, Proc. Soc. Exp. Biol. Med. 116, 912 (1964).

    Article  PubMed  CAS  Google Scholar 

  13. T. Seki, M. Sasazima, and Y. Watanabe, Yakugaku Zasshi 85, 962 (1965), 87, 296 (1967).

    PubMed  CAS  Google Scholar 

  14. T. Seki, Yakugaku Zasshi 87, 301 (1967).

    PubMed  CAS  Google Scholar 

  15. C. R. Ganellin, J. M. Loynes, H. F. Ridley, and R. G. W. Spickett, J. Med. Chem. 10, 826 (1967).

    Article  PubMed  CAS  Google Scholar 

  16. A. Brossi, H. Besendorf, B. Pellmont, M. Walter, and O. Schnider, Helv. Chim. Acta 43, 1459 (1960).

    Article  CAS  Google Scholar 

  17. A. Brossi, H. Besendorf, L. A. Pirk, and A. Rheiner, Jr., in: Analgetics (G. DeStevens, ed.), p. 281, Academic Press, New York, 1965.

    Google Scholar 

  18. A. Rheiner Jr., Experientia, 20, 488 (1964).

    Article  PubMed  CAS  Google Scholar 

  19. M. S. Sadove, S. M. Ali, and M. J. Schriffrin, Ill. Med. J. 117, 425 (1960).

    PubMed  CAS  Google Scholar 

  20. D. Lednicer and P. F. Von Voigtlander, J. Med. Chem. 22, 1157 (1979).

    Article  PubMed  CAS  Google Scholar 

  21. D. Lednicer, P. F. Von Voigtlander, and D. E. Emmert, J. Med. Chem. 23, 424 (1980).

    Article  PubMed  CAS  Google Scholar 

  22. D. Lednicer, P. F. Von Voigtlander, and D. E. Emmert, J. Med. Chem. 24, 404 (1981).

    Article  PubMed  CAS  Google Scholar 

  23. D. Lednicer and D. J. Du Champ, J. Org. Chem. 39, 2311 (1974).

    Article  CAS  Google Scholar 

  24. D. Lednicer, P. F. Von Voigtlander, and D. E. Emmert, J. Med. Chem. 24, 341 (1981).

    Article  PubMed  CAS  Google Scholar 

  25. R. C. Petersen and R. C. Stillman, Phencyclidine: A Review, National Institute of Drug Abuse, Washington, D. C., May 1978.

    Google Scholar 

  26. Y. Itzhak, A. Kalir, B. A. Weissman, and S. Cohen, J. Med. Chem. 24, 496 (1981).

    Article  PubMed  CAS  Google Scholar 

  27. J. Vignon, J.-P. Vincent, J.-N. Bidard, J.-M. Kamenka, P. Geneste, S. Monier, and M. Lazdunski, Eur. J. Pharmacol. 81, 531 (1982).

    Article  PubMed  CAS  Google Scholar 

  28. J.-P. Vincent, B. Kartalovski, P. Geneste, J.-M. Kamenka, and M. Lazdunski, Proc. Natl. Acad. Sci. USA 76, 4678 (1979).

    Article  PubMed  CAS  Google Scholar 

  29. G. Satzigner, Justus Liebigs Ann. Chem. 728, 64 (1969).

    Article  Google Scholar 

  30. G. Satzigner, Justus Liebigs Ann. Chem. 758, 43, 65 (1972).

    Google Scholar 

  31. L. Ernst, A. Schultz, W. Hecker, and W. Christ, Arch. Pharmacol. 313, Suppl. R29 (1980).

    Google Scholar 

  32. M. Herrmann, W. Steinbrecher, and W. Heldt, Arzneim Forsch. 20, 977 (1970).

    CAS  Google Scholar 

  33. B. Kay, Acta Anaesthesiol. Belg. 28, 5 (1977).

    PubMed  CAS  Google Scholar 

  34. A. L. Mauro and M. Shapiro, Curr. Ther. Res. 16, 725 (1974).

    PubMed  CAS  Google Scholar 

  35. W. P. Leary, A. C. Asmal and L. Bees, SA Med. J. 840 (1976).

    Google Scholar 

  36. D. McCarthy, Jr., and S. E. Harrigan, Excerpta Medica International Congress Series No. 399, Anaesthesiology. Proc. 6th World Congress of Anaesthesiology, Mexico City, April 1976.

    Google Scholar 

  37. N. Marenetra and M. C. F. Pain, Med. J. Aust. 1, 397 (1976).

    Google Scholar 

  38. G. Satzinger, Justus Liebigs Ann. Chem. 1965 (1974).

    Google Scholar 

  39. L. E. Overman, C. B. Petty, and R. J. Doedens, J. Org. Chem. 44, 4183 (1979).

    Article  CAS  Google Scholar 

  40. N. J. Harper, G. P. A. Veitch, and D. G. Wibberley, J. Med. Chem. 17, 1188 (1974).

    Article  PubMed  CAS  Google Scholar 

  41. J. Szmuszkovicz and P. F. Von Voigtlander, J. Med. Chem. 25, 1125 (1982).

    Article  PubMed  CAS  Google Scholar 

  42. P. F. Von Voigtlander, R. A. Lahti, and J. H. Ludens, J. Pharmacol. Exp. Ther. 224, 7 (1983).

    Google Scholar 

  43. Various authors, Arzneim. Forsch. 28 (1), 99-218 (1978).

    Google Scholar 

  44. W. Von Lintz, S. Erlaçin, E. Frankus, and H. Uragg, Arzneim. Forsch. 31, 1932 (1981).

    CAS  Google Scholar 

  45. A. F. Casy, N. J. Harper, and J. Dimmock, J. Chem. Soc. 3635 (1964).

    Google Scholar 

  46. J. P. Yardley, H. Fletcher, and P. B. Russell, Experientia 34, 1124 (1978).

    Article  PubMed  CAS  Google Scholar 

  47. R. J. Fragen and N. J. Caldwell, J. Clin. Pharmacol. 22, 459 (1982).

    Article  PubMed  CAS  Google Scholar 

  48. F. Camm, Eur. J. Pharmacol. 19, 259 (1981).

    Article  Google Scholar 

  49. A. R. Martin, A. P. Parulkar, D. J. Gusseck, L. J. Anderson, G. L. Grunewald, and A. I. White, J. Pharm. Sci. 58, 340 (1969).

    Article  PubMed  CAS  Google Scholar 

  50. V. S. Pai, A. P. Parulkar, A. R. Martin, and A. I. White, J. Pharm. Sci. 60, 201 (1971).

    Article  PubMed  CAS  Google Scholar 

  51. M. E. Freed, J. R. Potoski, E. H. Freed, C. L. Conklin, and J. L. Malis, J. Med. Chem. 16, 595 (1973).

    Article  PubMed  CAS  Google Scholar 

  52. M. E. Freed, J. R. Potoski, E. H. Freed, G. L. Conklin, and S. C. Bell, J. Med. Chem. 19, 479 (1976).

    Google Scholar 

  53. M. E. Freed, J. R. Potoski, G. L. Conklin, and S. C. Bell, J. Med. Chem. 19, 560 (1976).

    Article  PubMed  CAS  Google Scholar 

  54. M. Staquet, J. Clin. Pharmacol. 19, 392 (1979).

    Article  PubMed  CAS  Google Scholar 

  55. J. W. Downing, J. G. Brock-Utne, A. Barclay, and I. L. Schwegmann, Br. J. Anaesth. 53, 59 (1981).

    Article  PubMed  CAS  Google Scholar 

  56. B. T. Finncane, J. B. Floyd, D. J. Petro, and R. Braswell, Can. Anaesth. Soc. J. 29, 500 (1982).

    Google Scholar 

  57. H. P. Waest and J. W. Bellville, J. Clin. Pharmacol 19, 205 (1979).

    Article  Google Scholar 

  58. J. Dimaio, F. R. Ahmed, P. Schiller, and B. Belleau, in: Recent Advances in Receptor Chemistry (F. Gaultieri, M. Giannella, and C. Melchiorre eds.), p. 221, Elsevier/North Holland Biomédical Press, Amsterdam, 1979.

    Google Scholar 

  59. J. L. Malis, M. E. Rosenthale, and M. I. Gluckman, J. Pharmacol. Exp. Ther. 194, 488 (1975).

    PubMed  CAS  Google Scholar 

  60. B. S. Huegi, A. M. Ebnöther, E. Rissi, F. Gadient, D. Hauser, D. Roemer, R. C. Hill, H. H. Buescher, and T. J. Petcher, J. Med. Chem. 26, 42 (1983).

    Article  PubMed  CAS  Google Scholar 

  61. H. Fujimura and K. Kawai, Nippon Yakurigaku Zasshi 56, 514 (1960).

    Article  CAS  Google Scholar 

  62. K. Natsuka, H. Nakamura, H. Uno, and S. Umemoto, J. Med. Chem. 18, 1240 (1975).

    Article  PubMed  CAS  Google Scholar 

  63. H. Nishimura, J. Med. Chem. 21, 1265 (1978).

    Article  PubMed  Google Scholar 

  64. N. Shimokawa, H. Nakamura, K. Shimakawa, H. Minami, and H. Nishimura, J. Med. Chem. 22, 58 (1979).

    Article  PubMed  CAS  Google Scholar 

  65. H. Nakamura, K. Ishi, Y. Yokoyama, S. Motoyoshi, K. Natsuka, and M. Shimizu, J. Pharm. Pharmacol. 32, 635 (195 (1980).

    Google Scholar 

  66. G. Cignarella, E. Occelli, G. Maffii, and E. Testa, J. Med. Chem. 6, 385 (1965).

    Article  Google Scholar 

  67. G. Cignarella, E. Occelli, G. Cristiani, L. Paduano, and E. Testa, J. Med. Chem. 6, 764 (1963).

    Article  PubMed  CAS  Google Scholar 

  68. G. Cignarella, E. Occelli, and E. Testa, J. Med. Chem. 8, 326 (1965).

    Article  PubMed  CAS  Google Scholar 

  69. D. della Bella, V. Ferrari, V. Frigeni, and P. Lualdi, Nature New Biol. 241, 282 (1973).

    PubMed  Google Scholar 

  70. B. D. Cameron, L. F. Chasseaud, G. Hagdy, J. D. Lewis, V. H. Saggers, and I. P. Sword, Arzneim. Forsch. 23, 708 (1973).

    CAS  Google Scholar 

  71. J. V. Silverton and H. A. Lloyd, Acta Crystallog. (B) 31, 1576 (1975).

    Article  Google Scholar 

  72. E. L. May, Pharmacol. Res. Commun. 9 (1977) and refs. cited therein.

    Google Scholar 

  73. D. della Bella, G. Benelli, and A. Sassi, Pharmacol. Res. Commun. 8, 111 (1976).

    Article  PubMed  CAS  Google Scholar 

  74. C. B. Pert and S. H. Snyder, Proc. Natl. Acad. Sci. USA 70, 2243 (1973).

    Article  PubMed  CAS  Google Scholar 

  75. K. C. Rice, A. W. Jacobson, T. R. Burke Jr., B. S. Bajwa, R. A. Streaty, and W. A. Klee, Science 220, 314 (1983).

    Article  PubMed  CAS  Google Scholar 

  76. A. E. Jacobson, B. S. Bajwa, R. A. Streaty, W. A. Klee, and K. C. Rice, Life Sci. 33, Suppl. 1, 159 (1983).

    Article  Google Scholar 

  77. M. P. Mertes, A. A. Ramsay, P. E. Hanna, and D. D. Miller, J. Med. Chem. 13, 789 (1970).

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. University of Bath, Bath, UK

    Alan F. Casy & Robert T. Parfitt

  2. Canberra College of Advanced Education, Belconnen, ACT, Australia

    Robert T. Parfitt

Authors
  1. Alan F. Casy
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Robert T. Parfitt
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

Copyright information

© 1986 Springer Science+Business Media New York

About this chapter

Cite this chapter

Casy, A.F., Parfitt, R.T. (1986). Miscellaneous Groups of Analgesics. In: Opioid Analgesics. Springer, Boston, MA. https://doi.org/10.1007/978-1-4899-0585-7_11

Download citation

  • DOI: https://doi.org/10.1007/978-1-4899-0585-7_11

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4899-0587-1

  • Online ISBN: 978-1-4899-0585-7

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation