Syntheses and EGFR and HER-2 kinase inhibitory activities of 4-anilinoquinoline-3-carbonitriles: analogues of three important 4-anilinoquinazolines currently undergoing clinical evaluation as therapeutic antitumor agents.
The syntheses and biological evaluations of 4-anilinoquinoline-3-carbonitrile analogues of the three clinical lead 4-anilinoquinazolines Iressa, Tarceva, and CI-1033 are described. The EGFR and HER-2 kinase inhibitory activities and the cell growth inhibition of the two series are compared with each other and with the clinical lead EKB-569. Similar activities are observed between these two series.
Wissner
Allan
A
Chemical Sciences and Oncology and Immunoinflammatory Research, Wyeth Research, 401N. Middletown Road, Pearl River, NY 10965, USA. wissnea@wyeth.com
Brawner Floyd
M Brawner
MB
Rabindran
Sridhar K
SK
Nilakantan
Ramaswamy
R
Greenberger
Lee M
LM
Shen
Ru
R
Wang
Yu-Fen
YF
Tsou
Hwei-Ru
HR
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D002460:Cell Line; D003500:Cyclization; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D008958:Models, Molecular; D008968:Molecular Conformation; D009570:Nitriles / Q000138:chemical synthesis* / Q000494:pharmacology*; D011804:Quinolines / Q000138:chemical synthesis* / Q000494:pharmacology*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors*
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D066246:ErbB Receptors; D009570:Nitriles; D011804:Quinolines; D018719:Erb-b2 Receptor Tyrosine Kinases