Synthesis and antitumor activities of novel 1,4-disubstituted phthalazine derivatives

Article abstract of DOI:10.1016/j.ejmech.2010.05.016

In an attempt to develop potent and selective antitumor agents,a series of novel 1,4-disubstituted phthalazine derivatives was designed and synthesized. All the prepared compounds were screened for their cytotoxic activities against A549,HT-29 and MDA-MB-231 cell lines in vitro. Among them,seven compounds (7a7e,7j and 7i) displayed excellent selectivity for MDA-MB-231 cells with IC50 values in the nM range,a desirable range for pharmacological testing. The most promising compound,7a (IC50 = 3.79 μ M,2.32 μ M,0.84 nM),was 5.6-,10.8-and 6.9 × 10⁴-times more active than PTK-787 (IC50 = 21.16 μ M,22.11 μ M,57.72 μ M),respectively.