Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 2 de 2
Filter
Add more filters










Database
Language
Publication year range
1.
Bioorg Med Chem Lett ; 19(24): 6991-5, 2009 Dec 15.
Article in English | MEDLINE | ID: mdl-19879134

ABSTRACT

Inhibition of receptor tyrosine kinases (RTKs) such as vascular endothelial growth factor receptors (VEGFRs) and platelet-derived growth factor receptors (PDGFRs) has been validated by recently launched small molecules Sutent and Nexavar, both of which display activities against several angiogenesis-related RTKs. EphB4, a receptor tyrosine kinase (RTK) involved in the processes of embryogenesis and angiogenesis, has been shown to be aberrantly up regulated in many cancer types such as breast, lung, bladder and prostate. We propose that inhibition of EphB4 in addition to other validated RTKs would enhance the anti-angiogenic effect and ultimately result in more pronounced anti-cancer efficacy. Herein we report the discovery and SAR of a novel series of imidazo[1,2-a]pyrazine diarylureas that show nanomolar potency for the EphB4 receptor, in addition to potent activity against several other RTKs.


Subject(s)
Angiogenesis Inhibitors/chemistry , Imidazoles/chemistry , Phenylurea Compounds/chemistry , Protein Kinase Inhibitors/chemistry , Pyrazines/chemistry , Receptor, EphB4/antagonists & inhibitors , Urea/analogs & derivatives , Angiogenesis Inhibitors/pharmacology , Cell Line, Tumor , Humans , Imidazoles/pharmacology , Phenylurea Compounds/pharmacology , Protein Kinase Inhibitors/pharmacology , Pyrazines/pharmacology
2.
Bioorg Med Chem Lett ; 17(9): 2570-6, 2007 May 01.
Article in English | MEDLINE | ID: mdl-17317178

ABSTRACT

A series of 4'-substituted ribonucleoside derivatives has been prepared and evaluated for inhibition of hepatitis C virus (HCV) RNA replication in cell culture. The most potent and non-cytotoxic derivative was compound 28 (4'-azidocytidine, R1479) with an IC(50) of 1.28 microM in the HCV replicon system. The triphosphate of compound 28 was prepared and shown to be an inhibitor of RNA synthesis mediated by NS5B (IC(50)=320 nM), the RNA polymerase encoded by HCV. Data on related analogues have been used to generate some preliminary requirements for activity within this series of nucleosides.


Subject(s)
Antiviral Agents/chemistry , Chemistry, Pharmaceutical/methods , Cytidine/analogs & derivatives , Hepacivirus/genetics , Ribonucleosides/chemistry , Virus Replication/drug effects , Cytidine/pharmacology , Drug Design , Drug Evaluation, Preclinical , Inhibitory Concentration 50 , Models, Chemical , Molecular Conformation , Nucleosides/chemistry , RNA/chemistry , Uridine
SELECTION OF CITATIONS
SEARCH DETAIL
...