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

ABSTRACT: 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.

SUBMITTER: Zhang Y

PROVIDER: S-EPMC6154558 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature

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

Zhang Yan Y Liu Hongchun H Zhang Zhen Z Wang Ruifeng R Liu Tongchao T Wang Chaoyun C Ma Yuchi Y Ai Jing J Zhao Dongmei D Shen Jingkang J Xiong Bing B

Molecules (Basel, Switzerland) 20170405 4

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 discov ...[more]

PMID: 28379191

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