Investigation of novel 7,8-disubstituted-5,10-dihydro-dibenzo[b,e][1,4]diazepin-11-ones as potent Chk1 inhibitors

Lisa A Hasvold; Le Wang; Magdalena Przytulinska; Zhan Xiao; Zehan Chen; Wen-Zhen Gu; Philip J Merta; John Xue; Peter Kovar; Haiying Zhang; Chang Park; Thomas J Sowin; Saul H Rosenberg; Nan-Horng Lin

doi:10.1016/j.bmcl.2008.02.080

Investigation of novel 7,8-disubstituted-5,10-dihydro-dibenzo[b,e][1,4]diazepin-11-ones as potent Chk1 inhibitors

Bioorg Med Chem Lett. 2008 Apr 1;18(7):2311-5. doi: 10.1016/j.bmcl.2008.02.080. Epub 2008 Mar 6.

Authors

Lisa A Hasvold¹, Le Wang, Magdalena Przytulinska, Zhan Xiao, Zehan Chen, Wen-Zhen Gu, Philip J Merta, John Xue, Peter Kovar, Haiying Zhang, Chang Park, Thomas J Sowin, Saul H Rosenberg, Nan-Horng Lin

Affiliation

¹ Abbott Laboratories, Cancer Research, 100 Abbott Park Road, Dept. R4N6 AP10-307, Abbott Park, IL 60064-6101, USA. lisa.hasvold@abbott.com

PMID: 18358720
DOI: 10.1016/j.bmcl.2008.02.080

Abstract

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.

MeSH terms

Antineoplastic Agents / chemical synthesis
Antineoplastic Agents / pharmacology*
Benzodiazepinones / chemical synthesis
Benzodiazepinones / pharmacology*
Cell Line, Tumor / drug effects
Checkpoint Kinase 1
Drug Design*
Enzyme Inhibitors / chemical synthesis
Enzyme Inhibitors / pharmacology*
HeLa Cells
Humans
Models, Chemical
Protein Binding
Protein Kinases / metabolism*
Structure-Activity Relationship

Substances

Antineoplastic Agents
Benzodiazepinones
Enzyme Inhibitors
Protein Kinases
CHEK1 protein, human
Checkpoint Kinase 1