Design, Synthesis And Anticancer Activity Of 8-aminobenzofuran [3,2-d]pyrimidines

Benzofuro[3,2-d]pyrimidine compounds has a wide range of biological activity in antibacterial, anti-inflammatory, anticancer, antiviral and so on. It has been reported Benzofuro [3,2-d]pyrimidine compounds have tyrosine kinase inhibitory activities and were tested in Phase I clinical trial. In order to search for high active anticancer drugs, Thirty-seven novel benzofuro[3,2-d]pyrimidine compounds were designed and synthesized under the combined assistance of microwave and ultrasonic technique, starting from 5-nitro-salicylaldehyde as the raw material, reacted with hydroxylamine, dehydration, oxygen alkylation, rearrangement of closed loop, chloride, nitrogen alkylationa and reduction and so on. The reaction conditions were optimized processing, The structures of all the target molecules were characterized by EI-MS, ¹H NMR, ¹³C NMR or IR, the structure of A-2 was confirmed by X-ray diffraction analysis.The anticancer activities in vitro of compounds of A-1?3?B-1?7?C-1?4 were evaluated against COLO205 and MCF-7 cell lines, the target compounds of A-1?12?B-1?17?C-1?4 were screened against K562 cells using doxorubicin as positive control by the MTT method. The preliminary pharmacological results showed that the inhibitory effect of compound B-1?B-6?C-4 on both COLO205 and MCF-7 cell lines were remarkably, all of the compounds display a content of inhibition effect against K562 cells, the inhibitory effect of compound A-1?A-9?B-1?B-2?B-3?B-9?B-11?B-10?B-12?C-4 on K562 cells was remarkably. However the inhibition of the target compounds were not better than doxorubicin. The SAR showed that the inhibition of 8-amino benzofuran[3,2-d]pyrimidine derivatives was greater than the 8-nitro benzofuran[3,2-d]pyrimidine derivatives.