Poly(ADP-Ribose) Polymerase-1 (PARP-1) Inhibitors Based on a Tetrahydro-1(2H)-isoquinolinone Scaffold: Synthesis, Biological Evaluation and X-ray Crystal Structure

Abstract

The synthesis, activity and physical properties of two series of novel potent tetrahydro-1(2H)-isoquinolinone based PARP-1 inhibitors are described. The new structural classes with a non-planar ring system interact specifically with the PARP-1 protein at the nicotinamide-binding site.

Key words

medicinal chemistry - PARP inhibitors - structure-activity relationship - isoquinolinones - crystal structure

References

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1

New address: S. Peukert, Novartis Institutes for Biomedical Research, 250 Massachusetts Avenue, Cambridge, MA 02139, USA; E-Mail: [e-mail].