Synthesis and antitumor activity of some novel quinazoline derivatives bearing the biologically active thione moiety

Abstract

The reactivity of isothiocyanate 1 towards some nitrogen nucleophils was investigated. Thus, interaction of 1 with p-flouroaniline, benzylamine, 2-aminopyridine, and 4-aminoantipyrine yielded the corresponding quinazoline derivatives 3-7, respectively. Triazolo-quinazoline 10 was obtained in good yield via reaction of isothiocyanate 1 with thiosemicarbazide. When the isothiocyanate 1 was reacted with 1,2-phenylenediamine and/or 2,3-diaminopyrimidine the quinazoline derivatives 12, 13 were obtained. The biscompounds 16, 17 and 18 were isolated on hot reaction of 1 with 1,3-phenylenediamine or 2,6-diamino-4-hydroxy pyrimidine and/or 1,4 phenylenediamine (2:1 mol), while the quinazoline derivative 19 was obtained from the filtrate of the reaction mixture of 18. Assay for antitumor activity showed that compound 7 has a significant activity against Ehrlich ascites carcinoma tumor cells (in vitro); the percent for the non-viable cells was about 100%, 100% and 95% (significant) at a concentration of 100, 50 and 25 microg/ml, respectively.