N-замещенные производные 1<i>H</i>-пиримидин-4-она, обладающие анксиолитической активностью

Abstract

Íà îñíîâå ëîãèêî-ñòðóêòóðíîãî ïîäõîäà îñóùåñòâëåíî ìîëåêóëÿðíîå êîíñòðóèðîâàíèå N-1-çàìåùåííûõ ïðîèçâîäíûõ 1H-ïèðèìèäèí-4-îíà, âëèÿþùèõ íà ÖÍÑ.  ïðîöåññå ìîëåêóëÿðíîãî äîêèíãà îïðåäåëåíû âîçìîaeíûå ýíåðãèè îáðàçîâàíèÿ ëèãàíä-ðåöåïòîðíîãî êîìïëåêñà ñ D 2 -äîôàìèíîâûì è ÃÀÌÊ A -ðåöåïòîðîì. Ïîëó÷åííûå äàííûå ïîçâîëÿþò îöåíèòü âåðîÿòíîñòü ïðîÿâëåíèÿ ïñèõîòðîïíîé àêòèâíîñòè ó ìîäåëèðóåìûõ ñîåäèíåíèé. Íàèáîëåå ïåðñïåêòèâíûå èç íèõ ïîëó÷åíû ïî ìîäèôèöèðîâàííîé ìåòîäèêå ñèíòåçà. Äëÿ N-ãåòåðîöèêëè÷åñêèõ 1H-ïèðèìèäèí-4-îíîâ âûÿâëåíî âëèÿíèå ïðèðîäû ãåòåðîàòîìîâ íà âûõîä öåëåâûõ ïðîäóêòîâ. Èññëåäîâàííûå ñîåäèíåíèÿ I -IV, VI â äîçå 50 ìã/êã ïðîÿâëÿþò àíòèêîíôëèêòíîå äåéñòâèå. Íàèáîëüøàÿ àíòèêîíôëèêòíàÿ àêòèâíîñòü îòìå-÷åíà ó ìåðêàïòîòðèàçîëüíîãî ïðîèçâîäíîãî ïèðèìèäèí-4-îíà.Êëþ÷åâûå ñëîâà: öåëåíàïðàâëåííûé ñèíòåç; ìîëåêóëÿðíîå êîíñòðóèðîâàíèå; ïèðèìèäèí-4-îíû; D 2 -äîôàìèíîâûå è ÃÀÌÊ A -ðåöåïòîðû; àíêñèîëèòè÷åñêàÿ àêòèâíîñòü. Ïîñòóïèëà 18.06.15 The logical framework approach has been implemented in molecular designing of N-substituted derivatives of 1H-pyrimidin-4-one, affecting the CNS. The process of molecular docking was used to determine the possible energy of ligand -receptor complex formation with D 2 dopamine and GABA-A receptors. Using the obtained results, it is possible to estimate the probability of psychotropic activity manifestations in the model compounds. The most promising of these were synthesized using a modified method. For the obtained N-heterocyclic 1H-pyrimidin-4-ones, it was found that the nature of the heteroatoms influences the yield of target products. Some of the compounds (I -IV, VI) in a dose of 50 mg/kg produced anti-conflict action. The highest activity was observed for mercaptotriazole derivative of pyrimidin-4-one (II).