Vol 52, No 10 (2019)

An effective and convenient process for the preparation of ticagrelor (1), an antiplatelet drug, has been developed. The synthesis of 1 is a four-step reaction. Each reaction step was optimized individually to develop a scalable and industrial friendly process. The critical step to prepare intermediate 5 was optimized using the response surface methodology. One-pot reaction was used to telescope the next three steps, resulting in 75% overall yield in comparison to the initial 63% yield obtained from the stepwise isolation process. The feasibility and consistency of the improved process was verified by pilot-scale test.

A series of novel polycyclic N-amidoimides were synthesized by reacting 4-oxatetracyclo[5.3.2.0^2,6.0^8,10]dodec-11-ene-3,5-dione with hydrazides of benzoic acids, arylaminoacetic acid, and oxalic acid. The most pronounced antiviral activities against Vaccinia virus were observed for 4-hydroxy-N-(3,5-dioxo-4-azatetracyclo[5.3.2.0^{2, 6}.0^{8, 10}]dodec-11-en-4-yl)-3-nitrobenzamide, N-(3,5-dioxo-4-azatetracyclo[5.3.2.0^2,6.0^8,10]dodec-11-en-4-yl)-N′-[(3-trifluoromethyl)phenyl]ethanediamide, and N-(2,6-dimethylphenyl)-N′-(3,5-dioxo-4-azatetracyclo-5.3.2.0^2,6,0^8,10]dodec-11-en-4-yl)ethanediamide.

A series of close analogs of 4-hydroxy-6,7-dimethoxy-2-oxo-N-(pyridin-3-ylmethyl)-1,2-dihydroquinoline-3-carboxamide modified in the benzene moiety of the quinolone nucleus were synthesized to identify the structural fragments determining their analgesic effect. Results of pharmacological tests found that these chemical changes had a relatively weak influence on the analgesic activity of the tested compounds, leading to the conclusion that the modified fragment interacted insignificantly with the biological targets.

The radioprotective efficacy of recombinant flagellin (FL) and interleukin-1 beta (IL-1) administered in combinations for preventive or therapeutic purposes was studied in experiments on white mongrel mice. The drugs were administered i.p. at doses of 1 mg/kg (FL) and 50 μg/kg (IL-1β). Simultaneous administration of the drugs in the early stages before irradiation was shown to be most efficacious in terms of 30-day survival of mice exposed to x-rays at a dose of 7.5 Gy (100% survival of mice vs. 53% survival in the control group, p < 0.01). Sequential administration of FL before exposure and IL-1β after exposure increased survival of the mice by 40% (p < 0.05). The results indicated that combined use of biotechnological drugs for radioprotection was promising.

Methods for synthesizing new condensed pyrano[4, 3-b]pyridine derivatives from 2-methyl-2-ethyltetrahydropyran-4-one were developed. The neurotropic activities of the compounds were studied.

The ability of the decoction of meadowsweet flowers (Filipendula ulmaria, FU) to inhibit tumor development in female LIO rats was demonstrated using a radiation-induced carcinogenesis model (single γ-radiation dose of 4 Gy). Over half of tumors that developed in various locations in most (79.6%) irradiated control rats were malignant. The tumors were most often located in the breast. The carcinogenesis parameters for all locations (multiplicity of all tumors and incidence of malignant tumors) and especially for breast tumors (number of tumor-bearing rats, multiplicity of all and only malignant tumors) were reduced considerably in irradiated rats that received FU with drinking water over 16 months.

A quantitative determination method for total flavonoids in blood-red hawthorn leaves recalculated as vitexin 2″-O-rhamnoside using difference spectrophotometry at 392 nm was developed. The error of a single determination of total flavonoids in blood-red hawthorn leaves was ± 1.57% with confidence probability 95%. The contents of total flavonoids in blood-red hawthorn leaves varied from 2.65 ± 0.05 to 3.53 ± 0.06%.

The safety of interferons was assessed by analyzing 499 spontaneous reports in the Russian database from 2015 to 2017. The results led to the conclusion that the safety profile of systemic interferon preparations that are widely used in medical practice to treat multiple sclerosis is defined by data in spontaneous reports for the development of adverse reactions to them or the ineffectiveness of using them.

The kinetic factors influencing the hydroacylation of 2,6-dimethylnitrobenzene in the presence of Pd nanoparticles bound to anion exchangers were studied. A general scheme for catalytic synthesis of mepivacaine was proposed based on the obtained kinetic data. The one-step synthesis of mepivacaine was demonstrated to be efficient on various Pd-containing polymer catalysts.

A search for a modern method to determine the radiochemical purity of an ¹¹¹In-oxine radiopharmaceutical composition resulted in the selection of a chromatography system that could perform quality control rapidly, consistently, and more accurately than an extraction method. The simplicity of the method made it accessible and convenient for performing quality control in medical institutions immediately before labeling leukocytes and stem cells.