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5-Substituted pyridylisoxazoles as effective inhibitors of platelet aggregation

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Abstract

A series of 5-substituted 3-pyridylisoxazoles were synthesized using [3+2] cycloaddition of nitrile oxides to alkynes with variation of substituents at position 5 of the isoxazole ring without additional synthetic stages and with retention of 2-pyridyl-, 3-pyridyl, and 4-pyridyl substituents at position 3 of the isoxazole ring. Substituted pyridylisoxazoles are the potential antiaggregatory agents showing in vitro activity in the concentration range from 1•10−6 mol L−1 to 1•10−4 mol L−1 toward the human platelet rich blood plasma with arachidonic acid being used as the inductor of aggregation. These compounds do not act as cyclooxygenase or thromboxane synthase inhibitors, nor as thrombin inhibitors.

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Authors and Affiliations

  1. N. M. Emanuel Institute of Biochemical Physics, Russian Academy of Sciences, 4 ul. Kosygina, 119334, Moscow, Russian Federation

    O. V. Demina, A. A. Khodonov & S. D. Varfolomeev

  2. M. V. Lomonosov Moscow State University of Fine Chemical Technologies, 86 prosp. Vernadskogo, 119571, Moscow, Russian Federation

    O. V. Demina, A. A. Khodonov & V. I. Shvets

  3. National Research Center for Hematology, The Ministry of Health of the Russian Federation, 4 Novyi Zykovskii pr., 125167, Moscow, Russian Federation

    E. I. Sinauridze

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  1. O. V. Demina
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  2. A. A. Khodonov
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  3. E. I. Sinauridze
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  4. V. I. Shvets
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Correspondence to O. V. Demina.

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Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 9, pp. 2092–2113, September, 2014.

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Demina, O.V., Khodonov, A.A., Sinauridze, E.I. et al. 5-Substituted pyridylisoxazoles as effective inhibitors of platelet aggregation. Russ Chem Bull 63, 2092–2113 (2014). https://doi.org/10.1007/s11172-014-0707-3

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