Rational approaches to discovery of orally active and brain-penetrable quinazolinone inhibitors of poly(ADP-ribose)polymerase.

Article Details

Citation

Copy to clipboard

Hattori K, Kido Y, Yamamoto H, Ishida J, Kamijo K, Murano K, Ohkubo M, Kinoshita T, Iwashita A, Mihara K, Yamazaki S, Matsuoka N, Teramura Y, Miyake H

Rational approaches to discovery of orally active and brain-penetrable quinazolinone inhibitors of poly(ADP-ribose)polymerase.

J Med Chem. 2004 Aug 12;47(17):4151-4.

PubMed ID

15293985 [ View in PubMed

]

Abstract

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+.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
5-FLUORO-1-[4-(4-PHENYL-3,6-DIHYDROPYRIDIN-1(2H)-YL)BUTYL]QUINAZOLINE-2,4(1H,3H)-DIONE	Poly [ADP-ribose] polymerase 1	IC 50 (nM)	60	N/A	N/A	Details