Discovery of novel 7-azaindole derivatives bearing dihydropyridazine moiety as c-Met kinase inhibitors

• DOI: 10.1016/j.ejmech.2017.03.045
• Publication Date: 2017-03-23T19:48:34Z
• Authors: Qidong Tang; Linxiao Wang; Yongli Duan; Wenhui Wang; Shunmin Huang; Jia Zhi; Shuang Jia; Wufu Zhu; Ping Wang; Rong Luo; Pengwu Zheng
• Keywords: Moiety; Structure–activity relationship; IC50; Cancer cell lines

A series of 7-azaindole derivatives bearing the dihydropyridazine scaffold were synthesized and evaluated for their c-Met kinase inhibitory, and antiproliferative activity against 4 cancer cell lines (HT29, A549, H460, U87MG) were evaluated in vitro. Most compounds showed moderate to excellent potency. Compared to foretinib, the most promising analog 34 (c-Met IC50: 1.06 nM, a multitarget tyrosine kinase inhibitor) showed a 6.4-, 7.8-, and 3.2-fold increase in activity against HT29, A549, and H460 cell lines, respectively. Structure activity relationship studies indicated that mono-EWGs (such as R2 = F) at 4-position of moiety D was a key factor in improving the antitumor activity.