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Synthesis and Antithrombotic Activity Determination of (2-Methyl-4-[4-methyl-2-(4-trifluoromethylphenyl)-thiazole-5-ylmethylsulfanyl]phenoxy)acetic Acid Derivatives

https://doi.org/10.32362/2410-6593-2019-14-3-60-69

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Abstract

The article proposes an approach for obtaining the derivatives of hetarylmethylthioaryloxyalcane PPARS/fi agonists containing sulfoxide and sulfone fragments in the linker, the parent compound for the synthesis being GSK-516 - (2-methyl-4-[4-methyl-2-(4-trifiuoromethylph.enyl)-th.iazole-5-ylmethylsulfanyl]phenoxy)acetic acid obtained as a result of sequential S- and O-alkylation of mercaptocresol by thiazolyl methyl chloride and ethyl bromacetate at key stages. Derivatives of GSK-516, as well as sulfoxide and sulfone were synthesized for the first time by oxidating acyclic sulfur with meta-chloroperbenzoic acid. The structures of the synthesized compounds were confirmed by HPLC-MS, elemental analysis and JH, 13C NMR. The spectral characteristics of target compounds were compared by NMR. When passing from sulfide to sulfoxide and further to sulfone, it was found that the shift of the methylene group connecting the thiazole ring with the sulfur atom is moved to the weaker field. The antithrombotic activity of the obtained compounds was investigated by measuring platelet aggregation in platelet-rich plasma by the Bourne turbidimetric method. It was stated that sulfonic derivative GSK-516 has the highest antithrombotic activity.

About the Authors

D. V. Minin
D. Mendeleev University of Chemical Technology of Russia
Russian Federation

Dmitry V. Minin - Postgraduate Student of the Chair of Chemistry and Technology of Organic Synthesis/

9, Miusskaya sq., Moscow 125047


Competing Interests: not


S. V. Popkov
D. Mendeleev University of Chemical Technology of Russia
Russian Federation

Sergey V. Popkov - Ph.D. (Chemistry), Associate Professor, Head of the Chair of Chemistry and Technology of Organic Synthesis.

9, Miusskaya sq., Moscow 125047

Scopus Author ID 11940635000, ResearcherID A-5014-2016


Competing Interests: not


M. L. Burdeyny
D. Mendeleev University of Chemical Technology of Russia
Russian Federation

Maxim L. Burdeyny - Assistant of Professor of the Chair of Chemistry and Technology of Organic Synthesis.

9, Miusskaya sq., Moscow 125047

Scopus Author ID 36457454700, ResearcherID T-1483-2019


Competing Interests: not


V. M. Goncharov
D. Mendeleev University of Chemical Technology of Russia
Russian Federation

Valery M. Goncharov - D.Sc. (Chemistry), Associate Professor of the Chair of Chemistry and Technology of Organic Synthesis.

9, Miusskaya sq., Moscow 125047


Competing Interests: not


S. V. Vasilevsky
D. Mendeleev University of Chemical Technology of Russia
Russian Federation

Sergey V. Vasilevsky, Ph.D. (Chemistry), Associate Professor of the Chair of Chemistry and Technology of Organic Synthesis.

9, Miusskaya sq., Moscow 125047


Competing Interests: not


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Supplementary files

1. Fig. 1. Structural formula of PPAR agonists.
Subject
Type Research Instrument
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For citation:


Minin D.V., Popkov S.V., Burdeyny M.L., Goncharov V.M., Vasilevsky S.V. Synthesis and Antithrombotic Activity Determination of (2-Methyl-4-[4-methyl-2-(4-trifluoromethylphenyl)-thiazole-5-ylmethylsulfanyl]phenoxy)acetic Acid Derivatives. Fine Chemical Technologies. 2019;14(3):60-69. (In Russ.) https://doi.org/10.32362/2410-6593-2019-14-3-60-69

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