Discovery of a novel series of quinoxalines as inhibitors of c-Met kinase.
A series of quinoxaline inhibitors of c-Met kinase is described. The postulated binding mode was confirmed by an X-ray crystal structure and optimisation of the series was performed on the basis of this structure. Future directions for development of the series are discussed together with the identification of a novel quinoline scaffold.
Porter
John
J
UCB Celltech, 216 Bath Road, Slough SL1 3WE, United Kingdom. john.porter@ucb-group.com
Lumb
Simon
S
Lecomte
Fabien
F
Reuberson
James
J
Foley
Anne
A
Calmiano
Mark
M
le Riche
Kelly
K
Edwards
Helen
H
Delgado
Jean
J
Franklin
Richard J
RJ
Gascon-Simorte
Jose M
JM
Maloney
Alison
A
Meier
Christoph
C
Batchelor
Mark
M
D018360:Crystallography, X-Ray; D055808:Drug Discovery; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D019859:Proto-Oncogene Proteins c-met / Q000037:antagonists & inhibitors*; D011810:Quinoxalines / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D004791:Enzyme Inhibitors; D011810:Quinoxalines; D019859:Proto-Oncogene Proteins c-met