Discovery of 4-azaindoles as novel inhibitors of c-Met kinase.
A series of 4-azaindole inhibitors of c-Met kinase is described. The postulated binding mode was confirmed by an X-ray crystal structure and series optimisation was performed on the basis of this structure. Future directions for series development are discussed.
Porter
John
J
UCB Celltech, Slough, United Kingdom. john.porter@ucb.com
Lumb
Simon
S
Franklin
Richard J
RJ
Gascon-Simorte
Jose M
JM
Calmiano
Mark
M
Riche
Kelly Le
KL
Lallemand
Bénédicte
B
Keyaerts
Jean
J
Edwards
Helen
H
Maloney
Alison
A
Delgado
Jean
J
King
Lloyd
L
Foley
Anne
A
Lecomte
Fabien
F
Reuberson
James
J
Meier
Christoph
C
Batchelor
Mark
M
D045744:Cell Line, Tumor; D003198:Computer Simulation; D018360:Crystallography, X-Ray; D055808:Drug Discovery; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D019859:Proto-Oncogene Proteins c-met / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship
C522780:4-azaindole; D007211:Indoles; D047428:Protein Kinase Inhibitors; D019859:Proto-Oncogene Proteins c-met