title: Synthesis and biological evaluation of 4-anilinoquinolines as potent inhibitors of epidermal growth factor receptor.
abstract: 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.
authors.affiliation: Chemical Genomics Centre of the Max Planck Society, Otto-Hahn-Strasse 15, 44227 Dortmund, Germany.
authors.forename: Vijaykumar G
authors.initials: VG
authors.lastname: Pawar
authors.forename: Martin L
authors.initials: ML
authors.lastname: Sos
authors.forename: Haridas B
authors.initials: HB
authors.lastname: Rode
authors.forename: Matthias
authors.initials: M
authors.lastname: Rabiller
authors.forename: Stefanie
authors.initials: S
authors.lastname: Heynck
authors.forename: Willem A L
authors.initials: WA
authors.lastname: van Otterlo
authors.forename: Roman K
authors.initials: RK
authors.lastname: Thomas
authors.forename: Daniel
authors.initials: D
authors.lastname: Rauh
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D004353:Drug Evaluation, Preclinical; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000235:genetics; D020128:Inhibitory Concentration 50; D008958:Models, Molecular; D008968:Molecular Conformation; D009154:Mutation; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D011804:Quinolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D047428:Protein Kinase Inhibitors; D011804:Quinolines; D066246:ErbB Receptors