Синтез і протипухлинна активність 2-(4-aміно-5-метил-4H-[1,2,4]триазол-3-ілсульфаніл)-N-(5-R-бензилтіазол-2-іл)-ацетамідів

• Дата: 2015
• Автори: Ostapiuk, Yu. V., Matiychuk, V. S., Obushak, M. D.
• Формат: Стаття
• Мова: English
• Опубліковано: National University of Pharmacy 2015
• Теми: 2-aminothiazole; 1; 2; 4-triazole derivatives; chloroacetamides; arylation; Meerwein reaction; 4-amino-1; 4-triazole-3-thiole; anticancer activity; UDC 547.789; 2 аминотиазол; производные 1; 4-триазола; хлорацетамиды; арилирование; реакция Меервейна; 4-амино-[1; 4]триазол-3-тиол; противоопухолевая активность; УДк 547.789; 2-амінотіазол; похідні 1; 4-триазолу; хлорацетаміди; арилювання; реакція Меєрвейна; 4-аміно-[1; 4]триазол-3-тіол; протипухлинна активність; УДК 547.789
• Онлайн доступ: https://ophcj.nuph.edu.ua/article/view/ophcj.15.865
• Назва журналу: Journal of Organic and Pharmaceutical Chemistry

3-Aryl-2-chloropropanals 2a-h have been prepared by the reaction of arenediazonium chlorides 1a-h with acrolein in the conditions of Meerwein arylation (water-acetone, CuCl2 as a catalyst). These aldehydes react with thiourea by refluxing in ethanol to obtain 2-amino-5-R-benzyl-1,3-thiazoles 3a-h (R = 2-Cl, 3-Cl, 4-Cl, 3-CF3, 2,4-Cl2, 2,5-Cl2, 3,4-Cl2, 3-Cl-4-Me) with high yields. The resulting 2-aminothiazoles were acylated with chloroacetic acid chlorides to form 2-chloro-N-(5-aryl-1,3-thiazol-2-yl)acetamides 4a-h with the yields of 68-91%. By the reaction of compounds 4a-h with 4-amino-5-methyl-4H-1,2,4-triazole-3-thiole 5 a series of novel 2-(4-amino-5-methyl-4H-[1,2,4]triazol-3-ylsulfanyl)-N-(5-R-benzylthiazol-2-yl)-acetamides 6a-h (71-86%) have been synthesized. These compounds have been evaluated for their anticancer activity against 60 cancer lines in the concentration of 10 μM. The human tumour cell lines were derived from nine different cancer types: leukemia, melanoma, lung, colon, CNS, ovarian, renal, prostate, and breast cancers. Among all the derivatives, compounds 6a-c, 6e,f (R = 2-Cl, 3-Cl, 4-Cl, 2,4-Cl2, 2,5-Cl2) have been found to be active and have a high selectivity in relation to melanoma, while 2-(4-amino-5-methyl-4H-[1,2,4] triazol-3-ylsulfanyl)-N-[5-(2-chlorobenzyl)-thiazol-2-yl]-acetamide (6a) and 2-(4-amino-5-methyl-4H-[1,2,4]triazol-3-ylsulfanyl)-N-[5-(3,4-dichlorobenzyl)-thiazol-2-yl]-acetamide (6g) are active in relation to breast cancer.