Investigation of the effect of varying the 4-anilino and 7-alkoxy groups of 3-quinolinecarbonitriles on the inhibition of Src kinase activity.
Several 7-alkoxy-4-anilino-3-quinolinecarbonitriles were synthesized and evaluated for Src kinase inhibitory activity. Optimal inhibition of both Src enzymatic and cellular activity was seen with analogues having a 2,4-dichloro-5-methoxyaniline group at C-4. Compound 18, which has a 1-methylpiperidinemethoxy group at C-7, showed in vivo activity in a xenograft model.
Boschelli
Diane H
DH
Chemical and Screening Sciences, Wyeth Research, 401 N. Middletown Road, Pearl River, NY 10965, USA. bosched@wyeth.com
Ye
Fei
F
Wu
Biqi
B
Wang
Yanong D
YD
Barrios Sosa
Ana Carolina
AC
Yaczko
Deanna
D
Powell
Dennis
D
Golas
Jennifer M
JM
Lucas
Judy
J
Boschelli
Frank
F
D000818:Animals; D002460:Cell Line; D017690:Cell Transplantation; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D005347:Fibroblasts / Q000201:enzymology; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D051379:Mice; D008819:Mice, Nude; D009570:Nitriles / Q000138:chemical synthesis* / Q000494:pharmacology*; D011804:Quinolines / Q000138:chemical synthesis* / Q000494:pharmacology*; D051381:Rats; D013329:Structure-Activity Relationship; D014183:Transplantation, Heterologous; D019061:src-Family Kinases / Q000037:antagonists & inhibitors*
D004791:Enzyme Inhibitors; D007202:Indicators and Reagents; D009570:Nitriles; D011804:Quinolines; D019061:src-Family Kinases