Discovery of Substituted 1H-Pyrazolo[3,4-b]pyridine Derivatives as Potent and Selective FGFR Kinase Inhibitors

  • ACS Med Chem Lett. 2016 Apr 20;7(6):629-34. doi: 10.1021/acsmedchemlett.6b00066.
Bin Zhao  1 ,  Yixuan Li  1 ,  Pan Xu  1 ,  Yang Dai  1 ,  Cheng Luo  1 ,  Yiming Sun  1 ,  Jing Ai  1 ,  Meiyu Geng  1 ,  Wenhu Duan  1
Affiliations
  • 1. Department of Medicinal Chemistry, Division of Antitumor Pharmacology, and Drug Discovery and Design Center, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences , 555 Zu Chong Zhi Road, Shanghai 201203, China.
PMID: 27326339 DOI: 10.1021/acsmedchemlett.6b00066
Abstract

Fibroblast Growth Factor receptors (FGFRs) are important targets for Cancer therapy. Herein, we describe the design, synthesis, and biological evaluation of a novel series of 1H-pyrazolo[3,4-b]pyridine derivatives as potent and selective FGFR kinase inhibitors. On the basis of its excellent in vitro potency and favorable pharmacokinetic properties, compound 7n was selected for in vivo evaluation and showed significant antitumor activity in a FGFR1-driven H1581 xenograft model. These results indicated that 7n would be a promising candidate for further drug development.

Keywords
Cancer; FGFR; inhibitor; pyrazolo[3,4-b]pyridine.