Synthesis and evaluation of cerebroprotective activity of novel 6,7-dimethoxyquinazolin-4(3H)-one derivatives containing residues of amino acids and dipeptides

Neurodegenerative processes of the central nervous system are an important socially significant problem of modern society. They cause many diseases, such as Alzheimer's disease and cerebral ischemia, which significantly reduce the quality of human life and can lead to disability or death. The aim of this study was to synthesize novel 6,7-dimethoxyquinazolin-4(3H)-one derivatives with the remains of neuroactive amino acids and dipeptides in order to investigate their cerebroprotective properties. As a result of the study, 13 novel 6,7-dimetho-xyquinazolin-4(3H)-one derivatives were synthesized. Cerebral ischemia in rats was reproduced by irreversible right-sided occlusion of the middle cerebral artery using the Tamura method, and the area of brain necrosis was evaluated. Cognitive functions were evaluated in the Y-maze test. Among the studied quinazolinone derivatives, compounds 3i, 3j and 3k have the most pronounced cerebrotropic activity, which is not inferior to ethylmethylhydroxypyridine succinate in terms of pharmacological activity, making them promising objects for further research

Synthesis, in vitro and docking studies of 2-substituted 5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidine-4(3H)-one derivatives as agents for the treatment of Alzheimer's disease

Alzheimer's disease is a chronic neurodegenerative disease, which is characterized mainly by a progressive decrease in intellectual abilities, memory impairment and a change in a person's personality. Unfortunately, there are practically no medicines that act on pathogenesis of Alzheimer's disease. The development of new highly effective medicines for the treatment of this pathology is an actual area of pharmaceutical research. The aim of this work is to search among 2-substituted 5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidine-4(3H)-one effective compounds with an anticholinesterase and an antiamyloid activities. As a result, it was found that compounds 4d, 4e and 4f have the high anticholinesterase ability, which in their structure contain residues of hydroxy-methoxyphenyl fragments. Structures 4c, 4g, 4h, 4j, 4k, 4m, 4n and 4p showed slightly less activity, the effect of which did not differ statistically from that of Donepezil. Compounds 4c, 4e, 4k and 4m have the greatest ability to inhibit the formation of the amyloid, comparable to GV-971. It should be noted that the molecular docking data are consistent with the results of the determination of the anticholinesterase activity of the studied compounds obtained in vitro. Thus, the prospects for future studies of these compounds in the possibility of creating a pharmaceutical active substance for the treatment of neurodegenerative diseases have been revealed

Novel N-Benzothiazolylpyrazole Derivatives with Pronounced Antioxidant Activity

Осуществлено масштабирование синтеза ранее неизвестного 2-(3-метил‑4-нитрозо‑5-фенил‑1H‑пиразол‑1-ил)бензо[d]тиазола циклоконденсацией гидразинилбензотиазола с 2-гидроксимино‑1,3-бутандионом до граммовых масштабов. Показана возможность перехода от производного 1-(бензотиазол‑2-ил)-4-нитрозопиразола к ранее неизвестным нитро-, амино-, имино-, амидо- и арилазопроизводным. Впервые полученные соединения охарактеризованы с использованием методов ИК, ЯМР 1H, ЯМР 13C, COSY, HSQC, HMBC, электронной спектроскопии и хромато-масс- спектрометрии. Изучение антиоксидантной активности производных бензотиазолилпиразола показало, что активность азометиновых производных превосходит гесперидин и феруловую кислотуThis article describes the gramm-scale synthesis of novel 2-(3-methyl‑4-nitroso‑5-phenyl‑1H‑pyrazol‑1-yl)benzo[d]thiazole by cyclocondensation of hydrazinylbenzothiazole with 2-hydroxyimino‑1,3-butanedione. We show the possibility of transformation of 1-(benzothiazol‑2-yl)-4-nitrosopyrazole to new nitro-, amino-, imino-, amido- and arylazo derivatives. The obtained for the first time compounds were characterized by using IR, 1H NMR, 13C NMR, COSY, HSQC, HMBC, UV–Vis spectroscopy and chromatograhy-mass spectrometry. The study of the antioxidant activity of new benzothiazolylpyrazoles showed that azomethine derivatives have very good activity, which is compared to hesperidin and ferulic aci