4-(Aminoalkylamino)-3-benzimidazole-quinolinones as potent CHK-1 inhibitors.
CHK-1 is one of the key enzymes regulating checkpoints in cellular growth cycles. Novel 4-(amino-alkylamino)-3-benzimidazole-quinolinones were prepared and assayed for their ability to inhibit CHK-1. These compounds are potent cell permeable CHK-1 inhibitors and showed synergistic effect with a DNA-damaging agent, camptothecin.
Ni
Zhi-Jie
ZJ
Chiron Corporation, 4560 Horton Street, Emeryville, CA 94608, USA. zhi-jie_ni@chiron.com
Barsanti
Paul
P
Brammeier
Nathan
N
Diebes
Anthony
A
Poon
Daniel J
DJ
Ng
Simon
S
Pecchi
Sabina
S
Pfister
Keith
K
Renhowe
Paul A
PA
Ramurthy
Savithri
S
Wagman
Allan S
AS
Bussiere
Dirksen E
DE
Le
Vincent
V
Zhou
Yasheen
Y
Jansen
Johanna M
JM
Ma
Sylvia
S
Gesner
Thomas G
TG
D000478:Alkylation; D000586:Amination; D001562:Benzimidazoles / Q000737:chemistry*; D045744:Cell Line, Tumor; D000071877:Checkpoint Kinase 1; D018360:Crystallography, X-Ray; D006801:Humans; D020128:Inhibitory Concentration 50; D008958:Models, Molecular; D015394:Molecular Structure; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D011494:Protein Kinases / Q000737:chemistry / Q000378:metabolism*; D015363:Quinolones / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D001562:Benzimidazoles; D047428:Protein Kinase Inhibitors; D015363:Quinolones; C031000:benzimidazole; D011494:Protein Kinases; D000071877:Checkpoint Kinase 1