The search for new biologically active substances among derivatives of 3-mercapto-4-amino- 5-cyclohexyl-1,2,4-triazole(4h)

Abstract

The presentation of regioselectivity of 1-ethyl-3-[4-(6,7,8,9-tetrahydro-5Н-[1,2,4]triazolo[4,3-а]azepin-3-yl)phenyl]thiourea cyclization with α-bromoketone An important step in creation of potential drugs is to confirm the structure of the compounds synthesized. This requires the use of modern physical and physico-chemical methods of research. Nowadays a promising scientific direction for searching biologically active substances is the study of 2-R-imino-1,3-thiazoline derivatives.Aim. To study regioselectivity of the cyclization reaction of 1-ethyl-3-[4-(6,7,8,9-tetrahydro-5Н-[1,2,4]triazolo[4,3-а] azepin-3-yl)phenyl]thiourea with 2-bromo-1-phenylethanone.Results. The true structure of the interaction product was determined by the methods of 1 H NMR spectroscopy and X-ray analysis. Quantum chemical calculations of the electronic structure, geometry and thermodynamic parameters of the initial thiourea three tautomers were given. Activating energy of tautomer 1A belower than 1B one, the state of 1B has modest lower relative energy, consequently tautomer 1A is more credible state. Thus, the conclusion can be made that the reaction will proceed by 1-1A-3A.Experimental part. Quantum chemical calculations of the electronic structure, geometry and thermodynamic parameters of the initial thiourea three tautomers were determined by the density functional theory (DFT) methods using the GAUSSIAN W09 computer program. The effect of the solvent was considered within the framework of polarized continuum model (PCM).Conclusions. Based on the physico-chemical studies and quantum chemical calculations of the reaction cyclization direction the conclusion has been made that the cyclization reaction of 1-ethyl-3-[4-(6,7,8,9-tetrahydro-5Н-[1,2,4]triazolo [4,3-а]azepin-3-yl)phenyl]thiourea 1 with 2-bromo-1-phenylethanone 2 is regioselective, and it leads to formation of more thermodynamically advantageous (stable) isomer 3A.

Синтез и фармакологический потенциал новых производных 3-меркапто-4-амино(пирролил-1)-5-(тиенил-2)-1,2,4-триазола(4<i>H</i>)

“…Ïðè ýòîì íà âèä è ñèëó ôàðìàêîëîãè÷åñêîãî äåéñòâèÿ çíà÷èòåëüíîå âëèÿíèå îêàçûâàþò êàê çàìåñòèòåëè â àìèäíîé ôóíêöèè òèîàöåòàìèäíîãî îñòàòêà, òàê è ðàäèêàëû â 4 è 5 ïîëîaeåíèè òðèàçîëüíîãî êîëüöà. Èíòåðåñíûìè â ôàðìàêîëîãè÷åñêîì ïëàíå îêàçàëèñü ñîåäèíåíèÿ, ñîäåðaeàùèå â ïîëîaeåíèè 4 àìèíîãðóïïó è ïèððîëüíûé îñòàòîê, à òàêaeå öèêëîãåêñèëüíûé ðàäèêàë â ïîëîaeåíèè 5 (²²², IV), äëÿ êîòîðûõ îòìå÷åíî ïðîòèâîîïóõîëåâîå äåéñòâèå [8,9].…”

“…Äëÿ ñèíòåçà êëþ÷åâîãî èíòåðìåäèàòà (IX) ìû èñïîëüçîâàëè ìåòîäèêó, îïèñàííóþ ðàíåå â ðàáîòàõ [8,10]. Èñõîäíîé äëÿ ñèíòåçà ñòàëà òèîôåí-2-êàðáîíîâàÿ êèñëîòà (V), êîòîðóþ ýòåðèôèöèðîâàëè è ïîëó÷åííûé ýòèëîâûé ýôèð (VI) ïîäâåðãàëè ãèäðàçèíîëèçó.…”