title: Investigation of the effect of varying the 4-anilino and 7-alkoxy groups of 3-quinolinecarbonitriles on the inhibition of Src kinase activity.
abstract: 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.
authors.affiliation: Chemical and Screening Sciences, Wyeth Research, 401 N. Middletown Road, Pearl River, NY 10965, USA. bosched@wyeth.com
authors.forename: Diane H
authors.initials: DH
authors.lastname: Boschelli
authors.forename: Fei
authors.initials: F
authors.lastname: Ye
authors.forename: Biqi
authors.initials: B
authors.lastname: Wu
authors.forename: Yanong D
authors.initials: YD
authors.lastname: Wang
authors.forename: Ana Carolina
authors.initials: AC
authors.lastname: Barrios Sosa
authors.forename: Deanna
authors.initials: D
authors.lastname: Yaczko
authors.forename: Dennis
authors.initials: D
authors.lastname: Powell
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Golas
authors.forename: Judy
authors.initials: J
authors.lastname: Lucas
authors.forename: Frank
authors.initials: F
authors.lastname: Boschelli
mesh_terms: 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*
chemical_list: D004791:Enzyme Inhibitors; D007202:Indicators and Reagents; D009570:Nitriles; D011804:Quinolines; D019061:src-Family Kinases