Discovery and Biological Evaluation of a Series of Pyrrolo[2,3-b]pyrazines as Novel FGFR Inhibitors

oleh: Yan Zhang, Hongchun Liu, Zhen Zhang, Ruifeng Wang, Tongchao Liu, Chaoyun Wang, Yuchi Ma, Jing Ai, Dongmei Zhao, Jingkang Shen, Bing Xiong

Format: Article
Diterbitkan: MDPI AG 2017-04-01

Deskripsi

Abnormality of fibroblast growth factor receptor (FGFR)-mediated signaling pathways were frequently found in various human malignancies, making FGFRs hot targets for cancer treatment. To address the consistent need for a new chemotype of FGFR inhibitors, here, we started with a hit structure identified from our internal hepatocyte growth factor receptor (also called c-Met) inhibitor project, and conducted a chemical optimization. After exploring three parts of the hit compound, we finally discovered a new series of pyrrolo[2,3-b]pyrazine FGFR inhibitors, which contain a novel scaffold and unique molecular shape. We believe that our findings can help others to further develop selective FGFR inhibitors.