Synthesis and structure-activity relationships of 3-cyano-4-(phenoxyanilino)quinolines as MEK (MAPKK) inhibitors.
A series of 3-cyano-4-(phenoxyanilino)cyanoquinolines has been prepared as MEK (MAP kinase kinase) inhibitors. The best activity is seen with alkoxy groups at both the 6- and 7-positions. The lead compounds show low nanomolar IC50's against MAP kinase kinase, and have potent inhibitory activity in tumor cells.
Zhang
N
N
Chemical Sciences, Wyeth-Ayerst Research, Pearl River, NY 10965, USA. zhangn@war.wyth.com
Wu
B
B
Powell
D
D
Wissner
A
A
Floyd
M B
MB
Kovacs
E D
ED
Toral-Barza
L
L
Kohler
C
C
D000814:Aniline Compounds / Q000138:chemical synthesis / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D003110:Colonic Neoplasms / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D020128:Inhibitory Concentration 50; D020929:Mitogen-Activated Protein Kinase Kinases / Q000037:antagonists & inhibitors*; D009570:Nitriles / Q000138:chemical synthesis / Q000494:pharmacology*; D011804:Quinolines / Q000138:chemical synthesis / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
D000814:Aniline Compounds; D000970:Antineoplastic Agents; D009570:Nitriles; D011804:Quinolines; D020929:Mitogen-Activated Protein Kinase Kinases