SYNTHESIS, ANTIAGGREGANT AND ANTICOAGULANT ACTIVITY OF 2-[3-METHYL-8-MORPHOLINO-7-(THIETANYL-3)XANTHINYL-1]ACETIC ACID SALTS

DOI: https://doi.org/10.29296/25877313-2020-01-04
Issue: 
1
Year: 
2020

E.E. Klen Dr.Sc. (Pharm.), Associate Professor, Department of Pharmaceutical Chemistry with courses of analytical and toxicological chemistry, Bashkir State Medical University (Ufa) E-mail: klen_elena@yahoo.com V.A. Nebogatova Postgraduate Student, Department of Pharmaceutical Chemistry with courses of analytical and toxicological chemistry, Bashkir State Medical University (Ufa) E-mail: neb-veronika@inbox.ru L.I. Bashirova Post-graduate Student, Department of General and Clinical Pharmacology, Izhevsk State Medical Academy (Izhevsk) E-mail: lindadeireko@mail.ru A.L. Urakov Dr.Sc. (Med.), professor, Head of Department of General and Clinical Pharmacology, Izhevsk State Medical Academy (Izhevsk) E-mail: urakoval@live.ru A.V. Samorodov Dr.Sc. (Med.), Associate Professor, Department of Anesthesiology and Resuscitation with the course IDPO, Bashkir State Medical University (Ufa) E-mail: avsamorodov@gmail.com F.A. Khaliullin Dr.Sc. (Pharm.), Professor, Head of Department of Pharmaceutical Chemistry with courses of analytical and toxicological chemistry, Bashkir State Med-ical University (Ufa) Email: khaliullin_ufa@yahoo.com

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 synthe-sized 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.

Keywords: 
thietane
morpholine
xanthinyl-1-acetic acid
antiaggregant activity
anticoagulant activity
Lipinski's rule of five

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