Identification of aminoethyl pyrrolo dihydroisoquinolinones as novel poly(ADP-ribose) polymerase-1 inhibitors
| Autor: | Federica Orvieto, Danila Branca, Maria Cecilia Palumbi, Philip Jones, Ester Muraglia, Mauro Cerretani, Michael Rowley, Uwe Koch, Carlo Toniatti |
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| Rok vydání: | 2009 |
| Předmět: |
DNA Repair
Polymers DNA repair Chemistry Pharmaceutical Poly ADP ribose polymerase Clinical Biochemistry Pharmaceutical Science Antineoplastic Agents Poly(ADP-ribose) Polymerase Inhibitors Quinolones Crystallography X-Ray Ligands Biochemistry Inhibitory Concentration 50 Structure-Activity Relationship PARP1 Drug Discovery Humans Moiety Cytotoxicity Molecular Biology chemistry.chemical_classification Binding Sites biology Organic Chemistry NAD+ ADP-Ribosyltransferase Hydrogen Bonding Enzyme Models Chemical chemistry Enzyme inhibitor Drug Design biology.protein Molecular Medicine |
| Zdroj: | Bioorganic & Medicinal Chemistry Letters. 19:4042-4045 |
| ISSN: | 0960-894X |
| DOI: | 10.1016/j.bmcl.2009.06.031 |
| Popis: | PARP inhibitors have been demonstrated to retard intracellular DNA repair and therefore sensitize tumor cells to cytotoxic agents or ionizing radiation. We report the identification of a novel class of PARP1 inhibitors, containing a pyrrolo moiety fused to a dihydroisoquinolinone, derived from virtual screening of the proprietary collection. SAR exploration around the nitrogen of the aminoethyl appendage chain of 1 led to compounds that displayed low nanomolar activity in a PARP1 enzymatic assay. |
| Databáze: | OpenAIRE |
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