Synthesis and anticancer activities of 4-oxobenzopyrano[2,3-d]pyrimidines

Several 2-aryl-4-oxoxbenzopyrano[2,3-d]pyrimidin have previously been shown to exhibit in vivo antitumor activity in mice with P388 lymphocytic leukem ia. In the present study, a series of novel substituted benzopyrano[2,3-d]p yrimidines have been prepared and tested for cytotoxic activity against a p anel of cancer cell lines including the P388 lymphocytic leukemia cell line . The unsubstituted parent compound, some methoxylated derivatives and a cy clohexyl derivative all exhibited potent cytotoxic activity (IC50 values 0. 3-0.64 mu M). A number of derivatives, including the unsubstituted parent p yrimidine, were shown to cause a significant perturbation in cell cycle kin etics with an observed 2- to 3-fold increase in cells in the G(2)/M phase o f the cell cycle. Furthermore, a polymethoxylated derivative, 2-(3,4,5-trim ethoxyphenyl)-9-methoxy-4-oxo-2,3-dihydrobenzopyrano[2,3-d]pyrimidine 13, w as shown to be selectively active against a number of human ovarian cell li nes. [(C) 1999 Lippincott Williams & Wilkins.].