4-Anilino-3-cyanobenzo[g]quinolines as kinase inhibitors.
A series of 4-anilino-3-cyanobenzo[g]quinolines was prepared as potent kinase inhibitors. Compared with their bicyclic 4-anilino-3-cyanoquinoline analogues, the tricyclic 4-anilino-3-cyanobenzo[g]quinolines are less active against EGF-R kinase, equally active against MAPK kinase (MEK), and more active against Src kinase. For Src kinase inhibition, the best activity is obtained when both the 7- and 8-positions are substituted with alkoxy groups. Several of these kinase inhibitors show potent growth inhibitory activity in tumor cells.
Zhang
Nan
N
Chemical Sciences, Wyeth-Ayerst Research, Pearl River, NY 10965, USA. zhangn@war.wyeth.com
Wu
Biqi
B
Wissner
Allan
A
Powell
Dennis W
DW
Rabindran
Sridhar K
SK
Kohler
Constance
C
Boschelli
Frank
F
D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D007202:Indicators and Reagents; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors; D009570:Nitriles / Q000138:chemical synthesis* / Q000494:pharmacology*; D047428:Protein Kinase Inhibitors; D011804:Quinolines / Q000138:chemical synthesis* / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013379:Substrate Specificity; D019061:src-Family Kinases / Q000037:antagonists & inhibitors
D004791:Enzyme Inhibitors; D007202:Indicators and Reagents; D009570:Nitriles; D047428:Protein Kinase Inhibitors; D011804:Quinolines; D066246:ErbB Receptors; D019061:src-Family Kinases; D020928:Mitogen-Activated Protein Kinases