Synthetic Transformations of Higher Terpenoids. 39. Synthesis and Analgesic Activity of Isopimaric Acid Derivatives

New derivatives of isopimaric acid at the carboxylic acid were prepared. Their analgesic activity was studied in models of visceral and thermal pain. Isopimaric acid amides with aminoethanol and (2R)-(hydroxymethyl)pyrrolidine groups exhibited statistically significant analgesic activity in acetic acid-induced writhing (5 and 25 mg/kg doses) and hot-plate tests (25 mg/kg dose) that was comparable to that of diclofenac sodium (10 mg/kg dose). The new agents were characterized by low (LD50 > 1250 mg/kg) in vivo toxicity. Molecular modeling of possible interaction of the most active compounds with transmembrane G-protein-binding cannabinoid receptor CB2 was performed.

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Fig. 1.

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Acknowledgment

We thank the Khimiya Common Use Center, Siberian Branch, Russian Academy of Sciences, for the spectral and analytical studies. The work was financially supported by an RFBR grant and the Novosibirsk Regional Government (Project No. 19-43-540003).

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Correspondence to E. E. Shul’ts.

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For No. 38, see the literature [1].

Translated from Khimiya Prirodnykh Soedinenii, No. 3, May–June, 2021, pp. 404–410.

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Gromova, M.A., Kharitonov, Y.V., Borisov, S.A. et al. Synthetic Transformations of Higher Terpenoids. 39. Synthesis and Analgesic Activity of Isopimaric Acid Derivatives. Chem Nat Compd 57, 474–481 (2021). https://doi.org/10.1007/s10600-021-03391-1

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Keywords

  • diterpenoids
  • isopimaric acid
  • amides
  • esters
  • analgesic activity