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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

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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.

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Acknowledgments

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

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Authors and Affiliations

  1. Novosibirsk Institute of Organic Chemistry, Siberian Branch, Russian Academy of Sciences, Lavrentjev Av., 9, Novosibirsk, Russian Federation, 630090

    Ekaterina Nazimova, Alla Pavlova, Oksana Mikhalchenko, Irina Il’ina, Dina Korchagina, Tat’yana Tolstikova, Konstantin Volcho & Nariman Salakhutdinov

  2. Novosibirsk State University, Pirogova 2, Novosibirsk, Russian Federation, 630090

    Ekaterina Nazimova, Irina Il’ina, Konstantin Volcho & Nariman Salakhutdinov

Authors
  1. Ekaterina Nazimova
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  2. Alla Pavlova
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  3. Oksana Mikhalchenko
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  4. Irina Il’ina
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  5. Dina Korchagina
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  6. Tat’yana Tolstikova
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  7. Konstantin Volcho
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  8. Nariman Salakhutdinov
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Corresponding author

Correspondence to Konstantin Volcho.

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Nazimova, E., Pavlova, A., Mikhalchenko, O. et al. 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. Med Chem Res 25, 1369–1383 (2016). https://doi.org/10.1007/s00044-016-1573-3

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