Design and synthesis of novel pyrimidine hydroxamic acid inhibitors of histone deacetylases
| Autor: | Martin G. Rowlands, David Festus Charles Moffat, Lindsay Stimson, Vanessa L. Clark, Lindsey Ann Needham, Francesca Ann Day, Anthea Hardcastle, Judata Wibata, Sue Eccles, Deborah McNamara, Sanjay Patel, A. Donald, Wynne Aherne, Florence I. Raynaud |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
Pyrimidine
Transplantation Heterologous Clinical Biochemistry Pharmaceutical Science Hydroxamic Acids Biochemistry chemistry.chemical_compound Cell Line Tumor Drug Discovery medicine Humans Cancer epigenetics Histone H3 acetylation Molecular Biology Histone deacetylase 5 Hydroxamic acid biology Organic Chemistry Cancer medicine.disease Histone Deacetylase Inhibitors Pyrimidines Histone chemistry Drug Design biology.protein Molecular Medicine Histone deacetylase activity |
| Zdroj: | Bioorganic & Medicinal Chemistry Letters. 20:6657-6660 |
| ISSN: | 0960-894X |
| DOI: | 10.1016/j.bmcl.2010.09.016 |
| Popis: | Inhibition of histone deacetylase activity represents a promising new modality in the treatment of a number of cancers. A novel HDAC series demonstrating inhibitory activity in cell proliferation assays is described. Optimisation based on the introduction of basic amine linkers to effect good drug distribution to tumour led to the identification of a compound with oral activity in a human colon cancer xenograft study associated with increased histone H3 acetylation in tumour tissue. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect