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

  • Eur J Med Chem. 2010 Aug;45(8):3504-10. doi: 10.1016/j.ejmech.2010.05.016.
Shulan Zhang  1 ,  Yanfang Zhao ,  Yajing Liu ,  Dong Chen ,  Weihuan Lan ,  Qiaoling Zhao ,  Chengcheng Dong ,  Lin Xia ,  Ping Gong
Affiliations
  • 1. Key Laboratory of Original New Drug Design and Discovery of Ministry of Education, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenhe District, Shenyang, Liaoning 110016, PR China.
PMID: 20537434 DOI: 10.1016/j.ejmech.2010.05.016
Abstract

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 (7a-7e, 7j and 7i) displayed excellent selectivity for MDA-MB-231 cells with IC(50) values in the nM range, a desirable range for pharmacological testing. The most promising compound, 7a (IC(50) = 3.79 microM, 2.32 microM, 0.84 nM), was 5.6-, 10.8- and 6.9 x 10(4)- times more active than PTK-787 (IC(50) = 21.16 microM, 22.11 microM, 57.72 microM), respectively.