A.A. Spasov, L.V. Naumenko, A.Z. Saitgalina, F.A. Khaliullin

Disorders of the rheological properties of blood, in particular increased viscosity, often accompany cardiovascular diseases. Xanthine derivatives such as pentoxifylline are currently used successfully to correct increased blood viscosity syndrome. However, the search for new drugs to treat rheological disorders is very important. In order to find drugs to treat rheological disorders, methods to synthesize 2-(3-methylxanthinyl-8-thio)acetic acids containing a thietane ring in various states of sulfur oxidation and their derivatives were developed. 7-(1-Oxothietanyl-3)- and 7-(1,1-dioxothietanyl-3)-8-bromo-3-methylxanthines were prepared by oxidation of 8-bromo-3-methyl-7-(thietanyl-3)xanthine with hydrogenous peroxide. 2-[7-(Thietanyl-3)-, 2-[7-(1-oxothietanyl-3)- and 2-[7-(1,1-dioxothietanyl-3)-3-methylxanthinyl-8-thio]¬acetic acids were prepared by reaction of 8-bromo-3-methylxanthine containing a thietane ring with thioglycolic acid in ethanol in the presence of KOH. Reactions of the synthesized 2-(3-methylxanthinyl-8-thio)acetic acids with amines produced appropriate salts in 51-99% yield. The structures of the synthesized compounds were confirmed by elemental analysis and IR and PMR spectroscopy. The spectral data were consisted with the proposed structures. The rheological activity of the synthesized compounds was studied in vitro using the hyperthermal model of increased viscosity of rabbit blood. The reference compound was pentoxifylline. The effect of the compounds on erythrocyte aggregation was evaluated from the aggregation index. All the tested compounds exhibit rheological activity. Only compound (7) had practically the same rheological activity as pentoxifylline.