Synthesis and biological evaluation of some new imidazo[1,2-c]pyrimido [5,4-e]pyrimidin-5-amine derivatives.

The pyrimidine ring is a skeleton of particular interest that it is present in many compounds exhibiting biological and pharmaceutical activity. In the present work, some new pyrimidine derivatives were prepared via the formation of 5-oxo-4H-benzopyran (3), and its transformation to pyrimidine derivative (5) by reaction with benzamidine HCl. Compound 5 was subjected to react with thiophosgene to give isothiocyanate derivative 6. Phenacyl amine 7 was prepared by reaction of phenacyl bromide with hexamethylenetetramine under Delepine reaction condition. The reaction of compounds 6 and 7 in ethanol and drops of TEA afforded the imidazopyrmidinopyrimidine 8. Compound 8 was subjected to react with excess of POCl₃ to give its corresponding 5-chloro-2,8-diphenyl-10-(ptolyl) imidazo[1,2-c]pyrimido[5,4-e]pyrimidine (9). Then compound 9 was reacted with different amines to give N- (aryl)-2,8-diphenyl-10-(p-tolyl)imidazo[1,2-c]pyrimido [5,4-e]pyrimidin-5-amine (10 a-k). The new imidazopyrimidinopyrimidine derivatives, 10a-k, were first assessed for their anti-tumor properties towards two cancer cell lines, namely human hepatic malignancy (HepG2) and breast (MCF-7) by utilizing an MTT assay at a sole strength of 10 µM. Compounds 10d, 10e, 10f, 10h, and 10i displayed very strong activity, which contains in general, electron-withdrawing groups. [ABSTRACT FROM AUTHOR]