Investigation of novel 7,8-disubstituted-5,10-dihydro-dibenzo[b,e][1,4]diazepin-11-ones as potent Chk1 inhibitors.
The synthesis and structure-activity relationships (SAR) of Chk1 inhibitors based on a 5,10-dihydro-dibenzo[b,e][1,4]diazepin-11-one core are described. Specifically, an exploration of the 7 and 8 positions on this previously disclosed core afforded compounds with improved enzymatic and cellular potency.
Hasvold
Lisa A
LA
Abbott Laboratories, Cancer Research, 100 Abbott Park Road, Dept. R4N6 AP10-307, Abbott Park, IL 60064-6101, USA. lisa.hasvold@abbott.com
Wang
Le
L
Przytulinska
Magdalena
M
Xiao
Zhan
Z
Chen
Zehan
Z
Gu
Wen-Zhen
WZ
Merta
Philip J
PJ
Xue
John
J
Kovar
Peter
P
Zhang
Haiying
H
Park
Chang
C
Sowin
Thomas J
TJ
Rosenberg
Saul H
SH
Lin
Nan-Horng
NH
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D001570:Benzodiazepinones / Q000138:chemical synthesis / Q000494:pharmacology*; D045744:Cell Line, Tumor / Q000187:drug effects; D000071877:Checkpoint Kinase 1; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology*; D006367:HeLa Cells; D006801:Humans; D008956:Models, Chemical; D011485:Protein Binding; D011494:Protein Kinases / Q000378:metabolism*; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D001570:Benzodiazepinones; D004791:Enzyme Inhibitors; D011494:Protein Kinases; C000605867:CHEK1 protein, human; D000071877:Checkpoint Kinase 1