Substituted aminobenzimidazole pyrimidines as cyclin-dependent kinase inhibitors.
A series of aminobenzimidazole-substituted pyrimidines were synthesized and evaluated for biochemical activity against CDK1. A high-speed parallel synthesis approach enabled the identification of a potent lead series having improved potency in the CDK1 assay (IC(50)<10nM). Cell cycle analysis showed that the compounds induced a G2/M block. Docking studies were carried out with a CDK1 homology model, and provide a rationale for the observed activities.
Verma
Sharad
S
Department of Chemistry Research, Bayer Research Center, 400 Morgan Lane, West Haven, CT 06516, USA. sharad.verma.b@bayer.com <sharad.verma.b@bayer.com>
Nagarathnam
Dhanapalan
D
Shao
Jianxing
J
Zhang
Lei
L
Zhao
Jin
J
Wang
Yamin
Y
Li
Tindy
T
Mull
Eric
E
Enyedy
Istvan
I
Wang
Chunguang
C
Zhu
Qingming
Q
Altieri
Martha
M
Jordan
Jerold
J
Dang
Thu-Thi-Anh
TT
Reddy
Sanjeeva
S
D001562:Benzimidazoles / Q000737:chemistry* / Q000494:pharmacology; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors*; D006801:Humans; D047428:Protein Kinase Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D011743:Pyrimidines / Q000737:chemistry* / Q000494:pharmacology
D001562:Benzimidazoles; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D018844:Cyclin-Dependent Kinases