Synthesis and Biological Evaluation of Novel 4-Phenylaminobenzofuro[2,3-d]pyrimidine Derivatives

A series of novel 4-phenylaminobenzofuro[2,3-d]pyrimidine derivatives had been prepared and assessed for their in vitro antiproliferative activities against three lung cancer cell lines (A549, H460 and H1975). The bioassay results showed most of the designed compounds exhibited potential antiproliferation activities. Among them, compound 8f exhibited remarkable inhibitory activity against A549 and H460 cell lines with IC50 value of 2.54 mu M and 2.68 mu M, respectively, which was comparable to that of the positive control sorafenib (IC50 = 2.69 mu M for A549 and 3.71 mu M for H460). AO/EB staining suggests that compound 8f could induce apoptosis in A549 cells. Furthermore, cell cycle analyses show that compound 8f increased G(0)/G(1) A549 cells arrest in a concentration-dependent manner. The preliminary structure-activity relationships (SARs) studies indicated that mono-electron-withdrawing groups (mono-EWGs) on the phenyl ring are positive on the antitumor activity.