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Structure-Based Discovery of a Series of 5H-Pyrrolo[2,3-b]pyrazine FGFR Kinase Inhibitors
- Source :
- Molecules, Vol 23, Iss 3, p 698 (2018)
- Publication Year :
- 2018
- Publisher :
- MDPI AG, 2018.
-
Abstract
- Fibroblast growth factor receptors (FGFRs), a subfamily of receptor tyrosine kinases, are aberrant in various cancer types, and considered to be promising targets for cancer therapy. We started with a weak-active compound that was identified from our internal hepatocyte growth factor receptor (also called c-Met) inhibitor project, and optimized it with the guidance of a co-crystal structure of compound 8 with FGFR1. Through rational design, synthesis, and the biological evaluation of a series of 5H-pyrrolo[2,3-b]pyrazine derivatives, we discovered several potent FGFR kinase inhibitors. Among them, compound 13 displayed high selectivity and favorable metabolic properties, demonstrating a promising lead for further development.
- Subjects :
- cancer
FGFR
kinase inhibitor
pyrrolo[2,3-b]pyrazine
Organic chemistry
QD241-441
Subjects
Details
- Language :
- English
- ISSN :
- 14203049
- Volume :
- 23
- Issue :
- 3
- Database :
- Directory of Open Access Journals
- Journal :
- Molecules
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.3498663542d4080999bd8c4f7ff08bb
- Document Type :
- article
- Full Text :
- https://doi.org/10.3390/molecules23030698