Further studies on ethenyl and ethynyl-4-phenylamino-3-quinolinecarbonitriles: identification of a subnanomolar Src kinase inhibitor.
Several new ethynyl- and ethenyl-4-phenylamino-3-quinolinecarbonitriles were synthesized and tested for Src inhibition. Derivatives bearing an ethenyl or ethynyl substituent at C-6 showed decreased Src inhibitory activity. Incorporation of an ethenylpyridine N-oxide group at C-7 provided 20b, a 0.6 nM inhibitor of Src enzymatic activity with excellent cellular potency.
Barrios Sosa
Ana Carolina
AC
Wyeth Research, Chemical and Screening Sciences, 401 N. Middletown Road, Pearl River, NY 10965, USA. ana.barrios_sosa@roche.com
Boschelli
Diane H
DH
Wu
Biqi
B
Wang
Yan
Y
Golas
Jennifer M
JM
D000818:Animals; D020128:Inhibitory Concentration 50; D051379:Mice; D008819:Mice, Nude; D008956:Models, Chemical; D015394:Molecular Structure; D011804:Quinolines / Q000737:chemistry* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D019061:src-Family Kinases / Q000037:antagonists & inhibitors*
D011804:Quinolines; D019061:src-Family Kinases