This section provides background information related to the present disclosure which is not necessarily prior art.
Fibroblast growth factor (FGF) has been recognized as an important mediator of many physiological processes such as developmental morphogenesis and angiogenesis. The fibroblast growth factor receptor (FGFR) family is composed of four members (FGFR1-FGFR4), which are glycoprotein composed of extracellular immunoglobulin (Ig)-like domain, hydrophobic transmembrane domain, and the cytoplasmic part including tyrosine kinase domain. FGF binding leads to dimerization of FGFR, followed by activation of receptor autophosphorylation and downstream signaling pathways. Receptor activation is sufficient to regain and activate specific downstream signaling partners involved in the diverse process of regulation such as cell growth, cell metabolism and cell survival. Therefore, the FGF/FGFR signaling pathway has a multi-effect effect in many biological processes that are critical for tumor cell proliferation, migration, invasion and angiogenesis.
Vinyl indazoles are known in the field of cancer treatment, see WO 0210137 and WO 2003101968. FGFR inhibitors are also known in this art, see WO 2002022598.