Abstract

A series of novel amide and Schiffs base functionalized novel pyrido[1,2-a] pyrimidin- 4-one derivatives was prepared starting from 6-(thiophen-2-yl)/phenyl-4-(trifluoromethyl) pyridin- 2-amine 1a and 1b. These compounds on reacting with EMME afford compounds 2a and 2b, followed by cyclization to afford compounds 3a and 3b. Treatment of compounds 3a and 3b with hydrazine hydrate gave compounds 4a and 4b, which further reacted with different substituted aromatic aldehydes to give Schiff’s base derivatives 5a-j. In another way, compounds 3a, 3b by reacting with aliphatic amines give amide derivatives 6a-f. All the compounds, 5a-j and 6a-f, were screened against four human cancer cell lines (HeLa, COLO205, Hep G2, and MCF 7). Among all the derivatives, compounds 5c, 5e, 6a, and 6b showed promising anticancer activity.

Keywords: Pyridopyrimidin-4-one, 6-(thiophen-2-yl)/phenyl-4-(trifluoromethyl) pyridin-2-amine, EMME coupling, cyclization, Schiff’s base, anticancer activity.

Graphical Abstract