The synthesis and anticancer properties of 2-(4-amino-5-methyl-4H-[1,2,4]triazol-3-ylsulfanyl)-N-(5-R-benzylthiazol-2-yl)-acetamides

Yu. V. Ostapiuk, V. S. Matiychuk, M. D. Obushak

Abstract


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.


Keywords


2-aminothiazole; 1,2,4-triazole derivatives; chloroacetamides; arylation; Meerwein reaction; 4-amino-1,2,4-triazole-3-thiole; anticancer activity

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DOI: https://doi.org/10.24959/ophcj.15.865

Abbreviated key title: Ž. org. farm. hìm.

ISSN 2518-1548 (Online), ISSN 2308-8303 (Print)