Synthesis of acetamides bearing 3-aryl-3,4-dihydroquinazolin-4-one and 2-thioxothiazolidin-4-one moieties as novel derivatives

Abstract

In the present work, five ethyl 2-((4-oxo-3-aryl-3,4-dihydroquinazolin-2-yl)thio)acetate compounds (3a-e) were synthesized starting from anthranilic acid (1) via 2-thioxo-3-arylquinazolin-4(3H)-ones (2a-e). The reaction of (2a-e) with hydrazine hydrate to afford five 2-((4-oxo-3-aryl-3,4-dihydroquinazolin-2-yl)thio)acetohydrazide compounds (4a-e), respectively. Five new N-(4-oxo-2-thioxothiazolidin-3-yl)-2-((4-oxo-3-aryl-3,4-dihydroquinazolin-2-l)thio)acetamide compounds (5a-e) were synthesized based on the reaction of (4a-e) with thiocarbonyl-bis-thioglycolic acid and the yields of the synthesis reactions were observed to be about 58 to 72%. The chemical structure of the compounds was elucidated on the basis of IR, ¹H-NMR, ¹³C-NMR and HR-MS spectral data. The reaction of anthranilic acid and appropriately substituted phenyl isothiocyanates gave five 3-aryl-2-mercaptoquinazolin-4(3H)- one compounds with good yield. In the fact, the 2a-e compounds existed in the thione form, namely 3-aryl-2-thioxo-2,3-dihydroquinazolin-4(1H)- one by tautomerization.The results investigating the biological activity of the compounds contaning 2-thioxothiazolidin-4-one heterocycle (5a-e) indicated that the combination of two scaffolds being 3-arylquinazolin-4(3H)-one and 2-thioxothiazolidin-4-one did not form the compounds with cytotoxic activity against three human cancer cells including Hep-G2 cells, LU-1 cells and HeLa cells.