Microwave induced synthesis of novel 8,9-dihydro-7H-pyrimido[4,5-b][1,4]diazepines as potential antitumor agents.

A series of new racemic 4-amino-6-aryl-8-(1,3-benzodioxol-5-yl)-8,9-dihydro-7H-pyrimido[4,5-b][1,4]diazepines 4a-f and 4-amino-8-aryl-6-(1,3-benzodioxol-5-yl)-8,9-dihydro-7H-pyrimido[4,5-b][1,4]diazepines 5a-f were obtained regioselectively from the reaction of 4,5,6-triaminopyrimidine 1 with 1equiv of methylenedioxychalcones 2a-f and 3a-f, under microwave irradiation. Detailed NMR measurements confirm the high regioselectivity of this reaction. These compounds have been evaluated in the US National Cancer Institute (NCI) for their ability to inhibit approximately 60 different human tumor cell lines, where 4e, 5a and 5b presented remarkable activity against 47, 11 and 37 cancer cell lines, respectively, with the most important GI50 values ranging from 0.068 to 0.35 microM, in vitro assay.