This invention relates to compounds that inhibit protein tyrosine kinase activity. In particular the invention relates to compounds that inhibit the protein tyrosine kinase activity of growth factor receptors, resulting in the inhibition of receptor signaling, for example, the inhibition of VEGF receptor signaling and HGF receptor signaling. More particularly, the invention relates to compounds, compositions and methods for the inhibition of VEGF receptor signaling and HGF receptor signaling. The invention also provides compositions and methods for treating cell proliferative diseases and conditions.
[EN] INHIBITORS OF PROTEIN TYROSINE KINASE ACTIVITY<br/>[FR] INHIBITEURS DE L'ACTIVITÉ TYROSINE KINASE
申请人:METHYLGENE INC
公开号:WO2008035209A2
公开(公告)日:2008-03-27
(EN) The invention relates to quinoline and qumazoline derivatives that inhibit protein tyrosine kinase activity In particular the invention relates to compounds that inhibit the protein tyrosine kinase activity of growth factor receptors resulting in the inhibition of receptor signaling, for example, the inhibition of VEGF receptor signaling and HGF receptor signaling More particularly, the invention relates to compounds, compositions and methods for the inhibition of VEGF receptor signaling and HGF receptor signaling The invention also provides compositions and methods for treating cell proliferative diseases and conditions(FR) L'invention concerne des composé inhibant l'activité tyrosine kinase. Plus particulièrement, l'invention concerne des composés inhibant l'activité tyrosine kinase de récepteurs de facteurs de croissance, ce qui provoque l'inhibition de la signalisation de récepteurs, et notamment l'inhibition de la signalisation des récepteurs de VEGF et de la signalisation des récepteurs de HGF. Plus particulièrement, l'invention concerne des composés, des compositions et des méthodes destinés à inhiber la signalisation des récepteurs de VEGF et la signalisation des récepteurs de HGF. L'invention se rapporte en outre à des compositions et des méthodes de traitement de maladies et de pathologies caractérisées par une prolifération cellulaire.
Synthesis and Biological Evaluation of 4-Anilinoquinolines as Potent Inhibitors of Epidermal Growth Factor Receptor
作者:Vijaykumar G. Pawar、Martin L. Sos、Haridas B. Rode、Matthias Rabiller、Stefanie Heynck、Willem A. L. van Otterlo、Roman K. Thomas、Daniel Rauh
DOI:10.1021/jm901877j
日期:2010.4.8
The mutant receptor tyrosine kinase EGFR is a validated and therapeutically amenable target for genotypically selected lung cancer patients. Here we present the synthesis and biological evaluation of a series of 6- and 7-substituted 4-anilinoquinolines as potent type I inhibitors of clinically relevant mutant variants of EGFR. Quinolines 3a and 3e were found to be highly active kinase inhibitors in biochemical assays and were further investigated for their biological effect on EGFR-dependent Ba/F3 cells and non-small cell lung cancer (NSCLC) cell lines.