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Medicinal Chemistry Research

, Volume 23, Issue 12, pp 5063–5073 | Cite as

Highly potent analgesic activity of monoterpene-derived (2S,4aR,8R,8aR)-2-aryl-4,7-dimethyl-3,4,4a,5,8,8a-hexahydro-2H-chromene-4,8-diols

  • Irina Il’ina
  • Oksana Mikhalchenko
  • Alla Pavlova
  • Dina Korchagina
  • Tat’yana Tolstikova
  • Konstantin VolchoEmail author
  • Nariman Salakhutdinov
  • Evgeniy Pokushalov
Original Research

Abstract

New chiral heterocyclic compounds with a hexahydro-2H-chromene framework were synthesized by reactions of (1R,2R,6S)-3-methyl-6-(prop-1-en-2-yl)cyclohex-3-ene-1,2-diol with aromatic aldehydes in the presence of montmorillonite clay. The analgesic activity of the compounds was studied in vivo. The majority of these compounds showed significant analgesic activity in the acetic acid-induced writhing test; the compounds containing one hydroxy and one methoxy substituents also showed analgesic activity in the hot-plate test. (2S,4aR,8R,8aR)-2-(3-Hydroxy-4-methoxyphenyl)-4,7-dimethyl-3,4,4a,5,8,8a-hexahydro-2H-chromene-4,8-diol was as effective as the diclofenac sodium reference taken in the same dose in both tests. It has low acute toxicity and is very promising for further development.

Keywords

Terpene Chromene Heterocyclic compounds Analgesic activity Acetic acid-induced writhing test Hot-plate test 

Notes

Acknowledgments

Authors are grateful to the Presidium of Russian Academy of Sciences (program N 28.5), Presidium of Siberian Branch of Russian Academy of Sciences (Interdisciplinary integration Project No. 54), and Russian Foundation for Basic Research (Grant No. 13-03-00206a) for the financial support.

Supplementary material

44_2014_1071_MOESM1_ESM.doc (544 kb)
Supplementary material 1 (DOC 544 kb)

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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Irina Il’ina
    • 1
  • Oksana Mikhalchenko
    • 1
  • Alla Pavlova
    • 1
  • Dina Korchagina
    • 1
  • Tat’yana Tolstikova
    • 1
  • Konstantin Volcho
    • 1
    Email author
  • Nariman Salakhutdinov
    • 1
    • 2
  • Evgeniy Pokushalov
    • 3
  1. 1.Novosibirsk Institute of Organic ChemistrySiberian Branch, Russian Academy of SciencesNovosibirskRussian Federation
  2. 2.Novosibirsk State UniversityNovosibirskRussian Federation
  3. 3.State Research Institute of Circulation PathologyNovosibirskRussian Federation

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