Похідні [(N-арил)піперазиніл]бутилпіримідинів, які володіють нейротропними та актопротекторними властивостями

• Дата: 2016
• Автори: Andronati, S. A., Soboleva, S. G., Zamkova, A. V., Karasyova, T. L., Rakipov, I. M., Tsymbal, D. I.
• Формат: Стаття
• Мова: Russian
• Опубліковано: National University of Pharmacy 2016
• Теми: арилпіперазини; піримідини; афінітет; 5-НТ1А рецептори; нейротропні та актопротекторні властивості; УДК 615.015.11; 547.7/9
• Онлайн доступ: https://ophcj.nuph.edu.ua/article/view/ophcj.16.875
• Назва журналу: Journal of Organic and Pharmaceutical Chemistry

In this study the potential ligands of 5-HT1A receptors – arylpiperazines containing the residues of tetrahydropyrimidine as terminal fragments, compounds (1-6) and dihydropyrimidine – (7) have been synthesized. The structures of compounds 1-7 have been confi rmed by IR-spectroscopy, mass spectrometry and 1H-NMR-spectroscopy. Substances 2, 3, 4 and 7 inhibit the specifi c binding of the radioligand [3H]8-OH-DPAT with 5-HT1A receptors; it has been found that they have a pronounced affi nity for these receptors. In the confl ict situation test compounds of 1-5 and 7 showed anxiolytic properties, whereas phenylpiperazinil- and о-tolylpiperazinilbutyl-4-methyl-5-izopropyl-1,2,3,-6-tetrahydropyrimidine-2-thio-6-ones (1 and 2) exceeded the known drug buspirone by the level of the anxiolytic activity. The absence of this activity in compound 6 is probably due to the differences of substituents at N1 atom of the pyrimidine nucleus of compound 6 and other compounds of this series. It has been shown that on the model of hyperthermia all of these compounds in the dose range of 0.04-0.1 mg/kg possessed a high actoprotective activity increased the rat capacity work by 1.4-2.5 times compared to the control. The most active compound 3 in the ED50 dose of 0.04 mg/kg increased the duration of swimming in rats by 2.2 times (122%) compared to bemithylum. Some of the compounds (15 mg/kg) showed antihypoxic activity on the models of hemic (compounds 2-4, 7) and normobaric hypoxia (compounds 1, 2, 6) and exceeded bemithylym (33.5 mg/kg) by their activity. The compounds synthesized are low toxic with the LD50 value of 150-250 mg/kg.