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Medicinal Chemistry Research

, Volume 25, Issue 7, pp 1369–1383 | Cite as

Discovery of highly potent analgesic activity of isopulegol-derived (2R,4aR,7R,8aR)-4,7-dimethyl-2-(thiophen-2-yl)octahydro-2H-chromen-4-ol

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

Abstract

A large set of chiral heterocyclic compounds with the octahydro-2H-chromene scaffold was first obtained by a reaction of (−)-isopulegol and (+)-neoisopulegol with furan-2-carbaldehyde, thiophene-2-carbaldehyde and their derivatives and isomers in the presence of montmorillonite K10 clay. Most of the (−)-isopulegol-derived compounds exhibited a significant analgesic activity in the acetic acid-induced writhing test. Compound 3b obtained by a reaction of (−)-isopulegol with thiophene-2-carbaldehyde demonstrated a significant analgesic effect in this test within 15 min after oral administration at the dose of 1 mg/kg and retains the effect for at least 24 h. Compound 3b exhibited analgesic activity in the hot plate test also. A change in the sulfur atom position in the aromatic ring was found to lead to the effect reversal in the hot plate test.

Keywords

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

Notes

Acknowledgments

Authors are grateful to the Russian Foundation for Basic Research (Grant No 13-03-00206a) for the financial support.

Supplementary material

44_2016_1573_MOESM1_ESM.doc (216 kb)
Supplementary material 1 (DOC 216 kb)

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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Ekaterina Nazimova
    • 1
    • 2
  • Alla Pavlova
    • 1
  • Oksana Mikhalchenko
    • 1
  • Irina Il’ina
    • 1
    • 2
  • Dina Korchagina
    • 1
  • Tat’yana Tolstikova
    • 1
  • Konstantin Volcho
    • 1
    • 2
    Email author
  • Nariman Salakhutdinov
    • 1
    • 2
  1. 1.Novosibirsk Institute of Organic Chemistry, Siberian BranchRussian Academy of SciencesNovosibirskRussian Federation
  2. 2.Novosibirsk State UniversityNovosibirskRussian Federation

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