334949-22-3Relevant articles and documents
Synthesis of the Kinase Inhibitors Nintedanib, Hesperadin, and Their Analogues Using the Eschenmoser Coupling Reaction
Hanusek, Ji?í,Marek, Luká?,Svoboda, Jan,Váňa, Ji?í
, p. 10621 - 10629 (2021/07/31)
A novel synthetic approach involving an Eschenmoser coupling reaction of substituted 3-bromooxindoles (H, 6-Cl, 6-COOMe, 5-NO2) with two substituted thiobenzanilides in dimethylformamide or acetonitrile was used for the synthesis of eight kinase inhibitor
Design, synthesis, and evaluation of indolinones as triple angiokinase inhibitors and the discovery of a highly specific 6-methoxycarbonyl-substituted indolinone (BIBF 1120)
Roth, Gerald J.,Heckel, Armin,Colbatzky, Florian,Handschuh, Sandra,Kley, J?rg,Lehmann-Lintz, Thorsten,Lotz, Ralf,Tontsch-Grunt, Ulrike,Walter, Rainer,Hilberg, Frank
experimental part, p. 4466 - 4480 (2010/03/02)
Inhibition of tumor angiogenesis through blockade of the vascular endothelial growth factor (VEGF) signaling pathway is a newtreatment modality in oncology. Preclinical findings suggest that blockade of additional pro-angiogenic kinases, such as fibroblast and platelet-derived growth factor receptors (FGFR and PDGFR), may improve the efficacy of pharmacological cancer treatment. Indolinones substituted in position 6 were identified as selective inhibitors of VEGF-, PDGF-, and FGF-receptor kinases. In particular, 6-methoxycarbonyl-substituted indolinones showed a highly favorable selectivity profile. Optimization identified potent inhibitors of VEGF-related endothelial cell proliferation with additional efficacy on pericyctes and smooth muscle cells. In contrast, no direct inhibition of tumor cell proliferation was observed. Compounds 2 (BIBF 1000) and 3 (BIBF 1120) are orally available and display encouraging efficacy in in vivo tumor models while being well tolerated. The triple angiokinase inhibitor 3 is currently in phase III clinical trials for the treatment of nonsmall cell lung cancer.
