1.
Bioorg Med Chem Lett
; 20(1): 157-60, 2010 Jan 01.
Article
in English
| MEDLINE
| ID: mdl-19945875
ABSTRACT
A series of tetrahydro-beta-carbolines were identified by HTS as inhibitors of the kinesin Eg5. Molecular modeling and medicinal chemistry techniques were employed to explore the SAR for this series with a focus of removing potential metabolic liabilities and improving cellular potency.
Subject(s)
Carbolines/chemistry , Enzyme Inhibitors/chemistry , Kinesins/antagonists & inhibitors , Allosteric Regulation , Animals , Binding Sites , Carbolines/chemical synthesis , Carbolines/pharmacokinetics , Cell Line, Tumor , Crystallography, X-Ray , Drug Discovery , Enzyme Inhibitors/chemical synthesis , Enzyme Inhibitors/pharmacokinetics , High-Throughput Screening Assays , Humans , Kinesins/metabolism , Models, Molecular , Rats , Structure-Activity Relationship
2.
Bioorg Med Chem Lett
; 16(12): 3121-4, 2006 Jun 15.
Article
in English
| MEDLINE
| ID: mdl-16603354
ABSTRACT
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.
