Synthesis, antiaggregant and anticoagulant activity of 2-[3-methyl-8-morpholino-7-(thietanyl-3)xanthinyl-1]acetic acid salts


如何引用文章

全文:

开放存取 开放存取
受限制的访问 ##reader.subscriptionAccessGranted##
受限制的访问 订阅或者付费存取

详细

The purpose of the study was to develop methods for the synthesis of salts of 2-[3-methyl-8-morpholino-7-(thietanyl-3)xanthinyl-1]acetic acid, to study their effect on the hemostatic system, and to predict toxic risks and pharmacokinetic characteristics. 8-Morpholine derivative II was synthesized by reaction of ethyl 2-[8-bromo-3-methyl-7-(thietanyl-3)xanthinyl-1]acetate with morpholine. By hydrolysis of derivative II acid III was obtainedin good yield. Water-soluble salts IVa-g were synthesized using acid III and amines. The structure of synthesized compounds was determined by spectral methods (IR, NMR spectroscopy). According to the computer prediction salts IVa-g should not have toxic risks, most of them satisfy Lipinski's rule of five. In vitro investigation of the antiaggregant and anticoagulant activity of new substances indicated that compounds IVa,d exhibited antiaggregant activity and IVb,f - weak anticoagulant activity.

全文:

受限制的访问

作者简介

E. Klen

Bashkir State Medical University

Email: klen_elena@yahoo.com

V. Nebogatova

Bashkir State Medical University

Email: neb-veronika@inbox.ru

L. Bashirova

Izhevsk State Medical Academy

Email: lindadeireko@mail.ru

A. Urakov

Izhevsk State Medical Academy

Email: urakoval@live.ru

A. Samorodov

Bashkir State Medical University

Email: avsamorodov@gmail.com

F. Khaliullin

Bashkir State Medical University

Email: khaliullin_ufa@yahoo.com

参考

  1. ISTH Steering Committee for World Thrombosis Day. Thrombosis: a major contributor to the global disease burden. J. Thromb. Haemost. 2014; 12:1580-1590.
  2. Chan N.C. Antithrombotic Agents New Directions in Antithrombotic Therapy. Circ. Res. 2019; 124:426-436.
  3. Shanshan Huang, Yujie Ren, Xiuxiu Peng, Pingping Qian, Lingwei Meng. Computer-aid drug design, synthesis, and anticoagulant activity evaluation of novel dabigatran derivatives as thrombin inhibitors. Eur. J. Pharm. Sci. 2019; 137:104965.
  4. Debbabi M., Nimbarte V.D., Chekir S. et al. Design and synthesis of novel potent anticoagulant and anti-tyrosinasepy-ranopyrimidines and pyranotriazolopyrimidines: Insights from molecular docking and SAR analysis. Bioorg. Chem. 2019; 82:129-138.
  5. Самородов А.В., Камилов ФХ., Халиуллин Ф.А. и др. Результаты доклинических исследований новой циклогек-силаммониевой соли 2-[3-метил-7-(1,1-диоксотиетанил-3)-1-этилксантинил-8-тио]уксусной кислоты в отношении системы гемостаза в условиях in vivo. Вопросы биологической, медицинской и фармацевтической химии. 2016; 8:10-17.
  6. Халиуллин Ф.А., Шабалина Ю.В., Самородов А.В. и др. Синтез и антиагрегационная активность солей 2-[3-метил-1-этилксантинил-8-тио]уксусных кислот, содержащих тиетановый цикл. Химико-фармацевтический журнал. 2018; 52:29-32.
  7. Urakov A.L., Samorodov A. V. Kamilov F.Kh., et al. Hemo-statical activity of new benzylammonium salt 2-[3-methyl-1-n-propyl-7-(1,1-dioxotiethanyl-3)xantinyl-8-thio]acetic acid. Natl. J. Physiol. Pharm.Pharmacol. 2017; 7:1213-1218.
  8. Sander T., Freyss J., von Korff M., Rufener C. Data Warrior: An Open-Source Program For Chemistry Aware Data Visualization And Analysis. J. Chem. Inf. Model. 2015; 55:460-473.
  9. Клен Е.Э., Небогатова В.А., Халиуллин Ф.А. Исследование реакций алкилирования 8-бром-3-метил-7-(тиетанил-3)ксантина эфирами α-галогенуксусных кислот. Башкирский химический журнал. 2018; 25:25-29.
  10. Born G.V.R. Quantitative investigation into the aggregation of blood platelets. J. Physiol. 1962; 162:67-68.
  11. Руководство по проведению доклинических исследований лекарственных средств. Часть первая. М.: ГрифиК, 2012, 944 c.
  12. Lipinski C.A. Drug-like properties and the causes of poor solubility and poor permeability. J. Pharmacol. And Toxicol. Methods. 2000; 44:235-249.

补充文件

附件文件
动作
1. JATS XML
下载

版权所有 © Russkiy Vrach Publishing House, 2020