Journal of Medicinal Chemistry · 2004 · 95 citations · 4 references
Drug TargetBioorganic ChemistryOrally ActivePharmacotherapyChemical BiologyPharmaceutical ChemistryMedicinal ChemistryAdenosine-ribose Binding SiteNicotinamide-ribose Binding SiteInhibitory ActivityBrain-penetrable Quinazolinone InhibitorsBiochemistryMedicineRational ApproachesQuinazolinone DerivativesDrug DevelopmentPharmacologyNatural SciencesRational Drug DesignMolecular DockingDrug Discovery
A novel class of quinazolinone derivatives as potent poly(ADP-ribose)polymerase-1 (PARP-1) inhibitors has been discovered. Key to success was application of a rational discovery strategy involving structure-based design, combinatorial chemistry, and classical SAR for improvement of potency and bioavailability. The new inhibitors were shown to bind to the nicotinamide-ribose binding site (NI site) and the adenosine-ribose binding site (AD site) of NAD+.
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