2. Academic Validation
  3. Discovery of novel 7-azaindole derivatives bearing dihydropyridazine moiety as c-Met kinase inhibitors

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

  • Eur J Med Chem. 2017 Jun 16:133:97-106. doi: 10.1016/j.ejmech.2017.03.045.
Qidong Tang 1,  Linxiao Wang 2,  Yongli Duan 2,  Wenhui Wang 2,  Shunmin Huang 2,  Jia Zhi 2,  Shuang Jia 2,  Wufu Zhu 2,  Ping Wang 2,  Rong Luo 3,  Pengwu Zheng 4
Affiliations

Affiliations

  • 1 School of Pharmacy, Jiangxi Science and Technology Normal University, Nanchang 330013, PR China. Electronic address: tangqidongcn@126.com.
  • 2 School of Pharmacy, Jiangxi Science and Technology Normal University, Nanchang 330013, PR China.
  • 3 Jiangxi Province Institute of Materia Medica, Nanchang 330000, PR China.
  • 4 School of Pharmacy, Jiangxi Science and Technology Normal University, Nanchang 330013, PR China. Electronic address: zhengpw@126.com.
PMID: 28384549 DOI: 10.1016/j.ejmech.2017.03.045
Abstract

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.

Keywords

7-Azaindole derivatives; Anti-tumor; Dihydropyridazine; Receptor tyrosine kinase; c-Met.

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