[(N-Aryl)piperazinil]bythylpyrimidine derivatives with neurotropic and actoprotective properties

S. A. Andronati, S. G. Soboleva, A. V. Zamkova, T. L. Karasyova, I. M. Rakipov, D. I. Tsymbal


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.


arylpiperazine; pyrimidines; affi nity; 5-HT1A receptors; neurotropic and actoprotective properties


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