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Antiarrhythmic agents based on diterpenoid alkaloid lappaconitine. Protonation of N-deacethyllappaconitine in methanol solutions

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Abstract

The data on antiarrhythmic drugs based on diterpene alkaloid lappaconitine are summarized. N-Deacetyllappaconitine is the main metabolite of allapinin and a potential antiarrhythmics for intravenous use. The basicity of two nitrogen atoms of this compound and the possibility of obtaining mono- and di-salts with the example of hydrochlorides and hydrobromides having good solubility in water have been studied. It was shown using NMR spectroscopy and potentiometric titration that in the methanolic solutions the atom N(20) is protonated at the first step (pKb1 = 6.77, 25 °C) in the pH range of 6—7. The nitrogen of the primary aromatic amino group is protonated in the pH range of 2—3 (pKb2 = 2.18, 25 °C).

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Authors and Affiliations

  1. Ufa Institute of Chemistry, Ufa Federal Research Centre of the Russian Academy of Sciences, 71 prosp. Oktyabrya, 450054, Ufa, Russian Federation

    A. A. Akhiyarov, A. N. Lobov, S. P. Ivanov, L. V. Spirikhin, T. M. Gabbasov, E. M. Tsyrlina & M. S. Yunusov

  2. S. Yu. Yunusov Institute of the Chemistry of Plant Substances, Academy of Sciences of the Republic of Uzbekistan, 77 M. Ulugbek ul., 700170, Tashkent, Republic of Uzbekistan

    N. V. Valiev, A. Z. Sadikov & Sh. Sh. Sagdullaev

Authors
  1. A. A. Akhiyarov
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  2. A. N. Lobov
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  3. S. P. Ivanov
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  4. L. V. Spirikhin
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  5. T. M. Gabbasov
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  6. E. M. Tsyrlina
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  7. N. V. Valiev
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  8. A. Z. Sadikov
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  9. Sh. Sh. Sagdullaev
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  10. M. S. Yunusov
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Corresponding author

Correspondence to M. S. Yunusov.

Additional information

The spectra were recorded using the equipment of the Center for Collective Use “Chemistry” of the Ufa Institute of Chemistry of the UFRC RAS and RCCU “Agidel” of the UFRC RAS.

Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 3, pp. 0567–0571, March, 2020.

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Akhiyarov, A.A., Lobov, A.N., Ivanov, S.P. et al. Antiarrhythmic agents based on diterpenoid alkaloid lappaconitine. Protonation of N-deacethyllappaconitine in methanol solutions. Russ Chem Bull 69, 567–571 (2020). https://doi.org/10.1007/s11172-020-2800-0

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  • DOI: https://doi.org/10.1007/s11172-020-2800-0

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