Advertisement

Pharmaceutisch Weekblad

, Volume 7, Issue 4, pp 141–145 | Cite as

Analgesic activity of new pyrazine CH and NH acids and their Hydrophobic and electron donating properties

  • Roman Kaliszan
  • Bogusław Pilarski
  • Krzysztof OŚmiałowski
  • Halina Strzałkowska-Grad
  • Ewa Hać
Original Articles

Abstract

Analgesic efficacy was determined by the hot plate method for a group of 17 new pyrazine and 3 non-pyrazine CH and NH acids. The biological data were quantitatively related to the hydrophobicity of the compounds, expressed by fragmental constant, and to the orbital energy of the highest occupied molecular orbital, calculated quantumchemically. It has been found that the higher the electron donating properties, the more active is the agent, provided that its hydrophobicity allows it to reach its site of action. The results obtained support the charge transfer model for the biological interaction of analgesic agents.

Keywords

Public Health Internal Medicine Charge Transfer Molecular Orbital Biological Data 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Moncada S, Vane JR. Pharmacology and endogenous roles of prostaglandisendoperoxides, tromboxane A2, and prostacyclin. Pharmacol Rev 1978;30:293–331.PubMedGoogle Scholar
  2. 2.
    Shen TY. Toward more selective antiarthritic therapy. J Med Chem 1981;24:1–5.CrossRefPubMedGoogle Scholar
  3. 3.
    Brendel W. Ein neues statistisches Verfahren zur Suche nach essentiellen pharmakophoren Strukturen. Pharmazie 1983;38:116–9.PubMedGoogle Scholar
  4. 4.
    Brune K, Glatt M, Graf P. Mechanisms of action of antiinflammatory drugs. Gen Pharmacol 1976;7:27–33.PubMedGoogle Scholar
  5. 5.
    Neely WB, White HC, Rudzik A. Structure-activity relations in an imidazoline series prepared for their analgesic properties. J Pharm Sci 1968;57:1176–9.PubMedGoogle Scholar
  6. 6.
    KuchaŘ M, Rejholec V, Brunova B, Roubal Z, Nemecek O. Structure-activity relationships in a series of cinnamic acids in the stabilizing action on erythrocyte membrane. In: Tichy M, ed. Quantitative Structure-Activity Relationships. Budapest: Akademiai Kiado, 1976:45–7.Google Scholar
  7. 7.
    KuchaŘ M. The use of QSAR in the synthesis of antiinflammatory arylaliphatic acids. In: Knoll J, Darvas F, eds. Chemical Structure-Biological Activity Relationships. Quantitative Approaches. Budapest: Akademiai Kiado, 1980:15–24.Google Scholar
  8. 8.
    Miyashita Y, Seki T, Yotsui K-i, Yamazaki M, Sano M, Abe H, Sasaki S-i. Quantitative structure-activity relations in pyrazolylpyrimidine derivatives for their analgesic activities. Bull Chem Soc Jpn 1982;55:1489–92.Google Scholar
  9. 9.
    Mehler EL, Habicht J, Brune K. Quantum chemical analysis of structure-activity relationships in nonsteroidal antiinflammatory drugs. Mol Pharmacol 1982;22:525–8.PubMedGoogle Scholar
  10. 10.
    Mehler EL, Habicht J, Brune K. Structure-activity relationships in antiinflammatory phenols, benzoates and salicylates as obtained by quantum chemical methods. Agents Actions 1983;13:516–7.Google Scholar
  11. 11.
    Pilarski B, Foks H. Polish Patents P-232 409 and P-234 716.1981.Google Scholar
  12. 12.
    Pilarski B, Foks H, OŚmiałowski K, Kaliszan R. Studies on pyrazinyl-pyrazylidene tautomerism of pyrazineacetonitrile derivatives. Monatsh Chem 1984;115:179–85.CrossRefGoogle Scholar
  13. 13.
    Junek H, Wolny B. über einige Kondensationsreaktion von dimeren Malonitril, dimerem Cyanessigsäureäthyl bzw. methylester mit aromatischen Aldehyden. Monatsh Chem 1976;107:999–1006.CrossRefGoogle Scholar
  14. 14.
    Winter CA, Risley EA, Nuss GW. Carrageenan induced edema in hind paw of the rat as an assay for antiinflammatory drugs. Proc Soc Exp Biol Med 1962;111:544–7.PubMedGoogle Scholar
  15. 15.
    Cochin J. Methods for the appraisal of analgetic drugs for addiction liability. In: Burger A, ed. Selected Pharmacological Testing Methods. New York: Marcel Dekker Inc., 1968:121–7.Google Scholar
  16. 16.
    Rekker RF. The hydrophobic fragmental constant. Its derivation and application. A means of characterizing membrane systems. Amsterdam: Elsevier Science Publishers 1977:1–389.Google Scholar
  17. 17.
    Hansch C, Leo A. Substituent constants for correlation analysis in chemistry and biology. New York: John Wiley & Sons, 1979:18–43.Google Scholar
  18. 18.
    Kaliszan R. Chromatography in studies of quantitative structure-activity relationships. J Chromatogr 1981;220:71–83.CrossRefPubMedGoogle Scholar
  19. 19.
    Wheatley PI. The crystal and molecular structure of pyrazine. Acta Cryst 1957;10:182–7.CrossRefGoogle Scholar
  20. 20.
    Jones H, Fordice MW, Greenwald RB, et al. Synthesis and analgesic-antiinflammatory activity of some 4- and 5-substituted heteroarylsalicylic acids. J Med Chem 1978;21:1100–4.CrossRefPubMedGoogle Scholar

Copyright information

© Bohn, Scheltema & Holkema 1985

Authors and Affiliations

  • Roman Kaliszan
    • 1
  • Bogusław Pilarski
    • 1
  • Krzysztof OŚmiałowski
    • 1
  • Halina Strzałkowska-Grad
    • 1
  • Ewa Hać
    • 1
  1. 1.Faculty of PharmacyMedical AcademyGdańskPoland

Personalised recommendations