Discovery of novel pyrrolo[2,3-b]pyridine derivatives bearing 1,2,3-triazole moiety as c-Met kinase inhibitors

  • Bioorg Med Chem Lett. 2016 Apr 1;26(7):1680-4. doi: 10.1016/j.bmcl.2016.02.059.
Qidong Tang  1 ,  Linxiao Wang  2 ,  Yayi Tu  2 ,  Wufu Zhu  2 ,  Rong Luo  3 ,  Qidong Tu  2 ,  Ping Wang  2 ,  Chunjiang Wu  2 ,  Ping Gong  4 ,  Pengwu Zheng  5
Affiliations
  • 1. School of Pharmacy, Jiangxi Science and Technology Normal University, Nanchang 330013, PR China; Key Laboratory of Structure-Based Drug Design and Discovery of Ministry of Education, School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang 110016, PR China. Electronic address: [email protected].
  • 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. Key Laboratory of Structure-Based Drug Design and Discovery of Ministry of Education, School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang 110016, PR China.
  • 5. School of Pharmacy, Jiangxi Science and Technology Normal University, Nanchang 330013, PR China. Electronic address: [email protected].
PMID: 26923692 DOI: 10.1016/j.bmcl.2016.02.059
Abstract

A series of novel pyrrolo[2,3-b]pyridine derivatives bearing 1,2,3-triazole moiety were designed, synthesized, and evaluated for their c-Met kinase inhibitory activities and antiproliferative activities against 4 Cancer cell lines (HT-29, A549, MCF-7, and PC-3) in vitro. Most compounds showed moderate to excellent potency, with the most promising analog 34 showing a c-Met IC50 value of 1.68nM. Structure-activity relationship studies indicated that electron-withdrawing groups (X=CF3, R(1)=F, R(2)=4-F) were required to decrease the higher electron density on the 5-atom linker to a proper degree to improve the inhibitory activity.

Keywords
1,2,3-Triazole; Antiproliferative activity; Pyrrolo[2,3-b]pyridine derivatives; Synthesis; c-Met.