Synthesis and Biological Activity of Ethyl 2-[8-Arylmethylidenehydrazino-3-Methyl-7-(1-Oxothietan-3-YL)Xanth-1-YL]Acetates

Ethyl 2-[8-Arylmethylidenehydrazino-3-methyl-7-(1-oxothietan-3-yl)xanth-1-yl]acetates (IV) were synthesized via reactions of ethyl 2-[8-hydrazino-3-methyl-7-(1-oxothietan-3-yl)xanth-1-yl]acetic acid (III) with various benzaldehydes and acetophenones. The structures of the compounds were elucidated using IR and NMR spectroscopy and elemental analysis. The antiplatelet, anticoagulation, antioxidant, and anti-inflammatory activities were assessed in vitro and in laboratory animals to identify promising compounds exhibiting antiplatelet (hydrazone IVd) and antioxidant properties (hydrazone IVb). Both IVb and IVd according to in silico calculations were characterized by the absence of toxic risks (mutagenicity, oncogenicity, reproductive toxicity, local irritation) and had acceptable topological polar surface area so that they were promising.

This is a preview of subscription content, log in to check access.

References

  1. 1.

    F. A. Khaliullin, Yu. V. Shabalina, A. V. Samorodov, et al., Khim.-farm. Zh., 52, No. 1, 29 – 32 (2018), Pharm. Chem. J., 52, No. 1, 29 – 32 (2018).

  2. 2.

    A. L. Urakov, A. V. Samorodov, F. Kh. Kamilov, et al., Natl. J. Physiol. Pharm. Pharmacol., 7, No. 11, 1213 – 1218 (2017).

    CAS  Google Scholar 

  3. 3.

    M. Zygmunt, P. Zmudzki, G. Chlon-Rzepa, et al., Lett. Drug Des. Discovery, 11, 1204 – 1213 (2014).

    CAS  Article  Google Scholar 

  4. 4.

    M. Zygmunt, G. Chlon-Rzepa, E. Wyska, et al., Acta Pol. Pharm. Drug Res., 73, 761 – 770 (2016).

    CAS  Google Scholar 

  5. 5.

    T. Sander, J. Freyss, and M. von Korff, J. Chem. Inf. Model., 55, No. 2, 460 – 473 (2015); URL: http: //www.openmolecules.org/datawarrior/.

  6. 6.

    G. V. R. Born, J. Physiol., 162, 67 – 68 (1962).

    Google Scholar 

  7. 7.

    A. N. Mironov (ed.), Handbook for Preclinical Drug Trials [in Russian], Vol. 1, Grif i K, Moscow (2013).

    Google Scholar 

  8. 8.

    R. R. Farkhutdinov and S. I. Tevdoradze, Methods for Studying Chemiluminescence of Biological Material on an KhL-003 Chemiluminometer. Methods for Assessing Antioxidant Activity of Biologically Active Compounds [in Russian], RUDN, Moscow (2005), pp. 147 – 154.

  9. 9.

    V. V. Knyazev, V. S. Rogovskii, E. D. Sveshnikova, et al., Khim.-farm. Zh., 52, No. 3, 17 – 20 (2018); Pharm. Chem. J., 52, No. 3, 17 – 20 (2018).

  10. 10.

    V. S. Rogovskii, N. L. Shimanovskii, and A. I. Matyushin, Eksp. Klin. Farmakol., 75, No. 9, 37 – 41 (2012).

    CAS  PubMed  Google Scholar 

  11. 11.

    C. A. Lipinski, Drug Discovery Today: Technol., 1, No. 4, 337 – 341 (2004).

    CAS  Article  Google Scholar 

Download references

Author information

Affiliations

Authors

Corresponding author

Correspondence to E. E. Klen.

Additional information

Translated from Khimiko-Farmatsevticheskii Zhurnal, Vol. 54, No. 3, pp. 3 – 10, March, 2020.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Gurevich, K.G., Urakov, A.L., Klen, E.E. et al. Synthesis and Biological Activity of Ethyl 2-[8-Arylmethylidenehydrazino-3-Methyl-7-(1-Oxothietan-3-YL)Xanth-1-YL]Acetates. Pharm Chem J 54, 213–219 (2020). https://doi.org/10.1007/s11094-020-02182-2

Download citation

Keywords

  • oxothietanylxanthines
  • arylmethylidenehydrazines
  • antiplatelet, anticoagulant, antioxidant, anti-inflammatory activity
  • Lipinski’s rule of five