Submit Manuscript  

Article Details


Synthesis and Analgesic Activity of Amines Combining Diazaadamantane and Monoterpene Fragments

[ Vol. 13 , Issue. 8 ]

Author(s):

Konstantin Ponomarev, Ekaterina Morozova, Alla Pavlova, Evgeniy Suslov*, Dina Korchagina, Andrej Nefedov, Tat'yana Tolstikova, Konstantin Volcho and Nariman Salakhutdinov   Pages 773 - 779 ( 7 )

Abstract:


Background: It was found earlier that compounds combining diazaadamantane and monoterpene moieties possessed promising analgesic activity along with low acute toxicity and the lack of ulcerogenic activity.

Objective: In this paper, new structural analogues of the most active compounds were synthesized and evaluated for their analgesic activity.

Methods: Their structures were confirmed by various analytical methods, such as 1H and 13C NMR, HRMS. All of them were evaluated for analgesic activity at a dose of 20 mg/kg or less using acetic acid-induced writhing test and hot plate test.

Results: Some compounds showed analgesic activity in acetic acid-induced writhing test. One of the synthesized compounds demonstrated high analgesic activity in both tests with 46% effect in acetic acid-induced writhing test and 89% effect in hot plate test. Both structural fragments of this compound did not possess any analgesic effect at a dose of 20 mg/kg.

Conclusion: Structure-activity relationships indicated that the most active compound combines fragments of (–)-myrtenal and 6-amino-5,7-dimethyl-1,3-diazaadamantane. Both parts of the molecule are important for demonstrating analgesic activity.

Keywords:

Monoterpene, azaadamantane, adamantane, heterocyclic compounds, analgesic activity, acetic acid-induced writhing test, hot plate test.

Affiliation:

N.N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch, Russian Academy of Sciences, Novosibirsk, 630090, N.N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch, Russian Academy of Sciences, Novosibirsk, 630090, N.N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch, Russian Academy of Sciences, Novosibirsk, 630090, N.N. Vorozhtsov Novosibirsk Institute of Organic Chemistry of Siberian Branch of Russian Academy of Sciences, Novosibirsk, N.N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch, Russian Academy of Sciences, Novosibirsk, 630090, N.N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch, Russian Academy of Sciences, Novosibirsk, 630090, N.N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch, Russian Academy of Sciences, Novosibirsk, 630090, N.N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch, Russian Academy of Sciences, Novosibirsk, 630090, N.N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch, Russian Academy of Sciences, Novosibirsk, 630090

Graphical Abstract:



Read Full-Text article