The article presents the synthesis of 2-arylimino-4-methyl-2,3-dihydro-1,3-thiazoles via Hantzsch reaction of thioureas and 3-chloropentane-2,4-dione or ethyl 2-chloro-3-oxobutanoate. The structure of synthesized compounds was confirmed by LCMS, 1 H, and 13 C NMR spectra. Cardioprotective activity of synthesized thiazole derivatives were studied in vitro on the isolated rings of the thoracic aorta of laboratory rats. Based on pharmacological studies, the tested compounds possessed a moderate to high cardioprotective effect. A prospective 1-[2-(4-methoxyphenylimino)-4-methyl-3-(4-methylpiperazine-1-yl)-2,3-dihydro-1,3-thiazole-5-yl] ethan-1-one hydrochloride 4c was identified. The mentioned compound has delayed the development of constrictor responses of isolated rings of the thoracic rat aorta and exceeds the activity of L-carnitine by 18.2% and meldonium by 12.9%. The compound 4c may be proposed as a potential cardioprotective agent for in-depth pharmacological studies.

Экспериментальные модели заболеваний почек для исследований патогенетических механизмов и эффективности фармакологической коррекции на фоне коморбидной патологии Н. Н. Серединская, Н. Д. Филипец, Е. А. Филипец, К. В. Слободян, А. И. Гоженко Цель работы -освещение современных моделей заболеваний почек, сочетанных с другими патологическими состояниями, для экспериментальных исследований патогенетических механизмов и эффективности фармакологической коррекции.Рассмотрены экспериментальные модели, которые целесообразно использовать для исследования патогенеза и эффективности средств фармакологической коррекции коморбидной патологии. Акцентировано внимание на моделях, воспроизводящих кардиоренальный, гепаторенальный синдром и полиорганное гипоксическое гистогемическое повреждение у лабораторных крыс. Эти модели характеризуются легким моделированием, воспроизведением патогенеза коморбидных заболеваний, наличием острого и хронического периода повреждения, индуцированного антибиотиком доксорубицином или экотоксикантами -сулемой, нитритом натрия, 2,4-динитрофенолом.Выводы. Представленные модели кардиоренального, гепаторенального синдромов и гипоксического повреждения организма являются оптимальными для проведения многоцелевых исследований физиологического, патофизиологического, фармакологического направлений с максимальным приближением результатов к клинико-терапевтическим особенностям коморбидной патологии.The aim of our study is to report about modern models of kidney diseases associated with other pathological conditions for experimental studies of pathogenic mechanisms and efficacy of pharmacological correction.The study deals with experimental models reasonably to be applied in investigation of comorbid pathology pathogenesis and efficacy of its pharmacological correction. The attention is focused on the models of cardio-renal, hepatic-renal syndromes and multiple organ hypoxic histochemical injury simulated in laboratory rats. These models are characterized by easy modeling, simulation of comorbidity pathogenesis, acute and chronic periods of diseases available, induced by the antibiotic Doxorubicin or exotoxins -corrosive sublimate, sodium nitrite, and 2,4-dinitrophenol.Conclusions. The models of cardio-renal, hepatic-renal syndromes and hypoxic histochemical injury of the body are found to be optimal to perform multipurpose studies of physiological, pathophysiological, pharmacological directions with maximal similarity of the results obtained to clinical-therapeutic peculiarities of comorbid pathology.Експериментальні моделі захворювань нирок для досліджень патогенетичних механізмів та ефективності фармакологічної корекції на тлі коморбідної патології Н. М. Серединська, Н. Д. Філіпець, О. О. Філіпець, К. В. Слободян, А. І. Гоженко Мета роботи -висвітлення сучасних моделей захворювань нирок, що поєднані з іншими патологічними станами, для експериментальних досліджень патогенетичних механізмів та ефективності фармакологічної корекції.Розглянуті експериментальні моделі, які доцільно використовувати для дослідження пат...

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With the interaction of drugs belonging to different pharmacotherapeutic groups – nonsteroidal anti-inflammatory and antihypertensive – against the background of comorbid arterial hypertension with rheumatoid arthritis, the activity and safety of drugs may change with their combined use. Changes in the analgesic activity of nonsteroidal anti-inflammatory drugs, different in their selectivity to the types of cyclooxygenase (diclofenac, nimesulide and celecoxib), under the conditions of their long-term combined use with amlodipine in different periods of inflammation against the background of hypertension should be studied. Using the model of adjuvant arthritis comorbid with hypertension, in experiments on nonlinear mature white rats, the threshold of pain sensitivity has been determined by means of the “tail flick” test. Hypertension was caused by salt load with 1% sodium chloride solution for drinking with free access to it. Adjuvant arthritis was induced by the introduction of complete Freund’s adjuvant into the plantar aponeurosis of the hind limb of each animal with the established arterial hypertension. Against the background of arterial hypertension and comorbid pathology, there was an increase in the threshold of pain sensitivity observed in rats, which indicated the development of hypoalgesia. When combined, amlodipine enhanced the analgesic activity of diclofenac during 60 days of observation, slightly heightened the analgesic effect of nimesulide – up to 42 days, the effect of Celecoxib – in the acute period and the period of manifestation of adjuvant arthritis against the background of hypertension. The antinociceptive effect of diclofenac with amlodipine and celecoxib with amlodipine exceeded the analgesic effect of the combined nimesulide with amlodipine use against the background of comorbid pathology. The results obtained can be taken into account under the conditions of prescribing drugs belonging to the studied pharmacotherapeutic groups. It is likely that the use of diclofenac for analgesia against the background of comorbid conditions is only appropriate in the acute period of rheumatoid arthritis. The use of nimesulide to achieve an analgesic effect in the recurrence of rheumatoid arthritis against the background of hypertension is appropriate in the acute period and in the period of the inflammatory process attenuation. A highly selective coxib group cyclooxygenase-2 inhibitor, celecoxib, can reduce pain during the acute period of arthritis and during the manifestation of an inflammatory reaction that has developed against the background of arterial hypertension.