Identification of selective inhibitors of cyclin dependent kinase 4.
A new structural type of kinase inhibitor, containing a benzocarbazole nucleus, has been identified. Members of the series are selective for inhibition of the cyclin dependent kinase family of enzymes. Although the cdks are highly homologous, representatives of the series showed intra-cdk selectivities, especially for cdk4. SAR studies elucidated the important features of the molecules for inhibition.
Carini
D J
DJ
DuPont Pharmaceuticals Company, Wilmington, DE 19880, USA. thais.m.sielecki@dupontpharma.com
Kaltenbach
R F
RF
Liu
J
J
Benfield
P A
PA
Boylan
J
J
Boisclair
M
M
Brizuela
L
L
Burton
C R
CR
Cox
S
S
Grafstrom
R
R
Harrison
B A
BA
Harrison
K
K
Akamike
E
E
Markwalder
J A
JA
Nakano
Y
Y
Seitz
S P
SP
Sharp
D M
DM
Trainor
G L
GL
Sielecki
T M
TM
D002227:Carbazoles / Q000737:chemistry / Q000494:pharmacology*; D051358:Cyclin-Dependent Kinase 4; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D008968:Molecular Conformation; D011518:Proto-Oncogene Proteins; D013329:Structure-Activity Relationship
D002227:Carbazoles; D004791:Enzyme Inhibitors; D011518:Proto-Oncogene Proteins; D051358:Cyclin-Dependent Kinase 4; D018844:Cyclin-Dependent Kinases