Quinazolines as cyclin dependent kinase inhibitors.
Quinazolines have been identified as inhibitors of CDK4/D1 and CDK2/E. Aspects of the SAR were investigated using solution-phase, parallel synthesis. An X-ray crystal structure was obtained of quinazoline 51 bound in CDK2 and key interactions within the ATP binding pocket are defined.
Sielecki
T M
TM
The DuPont Pharmaceuticals Company, Wilmington, DE 19880-0500, USA. thais.m.sielecki@dupontpharma.com
Johnson
T L
TL
Liu
J
J
Muckelbauer
J K
JK
Grafstrom
R H
RH
Cox
S
S
Boylan
J
J
Burton
C R
CR
Chen
H
H
Smallwood
A
A
Chang
C H
CH
Boisclair
M
M
Benfield
P A
PA
Trainor
G L
GL
Seitz
S P
SP
D001667:Binding, Competitive / Q000187:drug effects; D002460:Cell Line; D018360:Crystallography, X-Ray; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors*; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D008958:Models, Molecular; D011799:Quinazolines / Q000138:chemical synthesis*; D013329:Structure-Activity Relationship
D004791:Enzyme Inhibitors; D011799:Quinazolines; D018844:Cyclin-Dependent Kinases