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Synthesis 2005(9): 1550-1554  
DOI: 10.1055/s-2005-865324
PAPER
© Georg Thieme Verlag Stuttgart · New York

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

Stefan Peukert*, Uwe Schwahn, Stefan Güssregen, Herman Schreuder, Armin Hofmeister
Aventis Pharma Deutschland GmbH, a company of the sanofi-aventis group, TD Cardiovascular, TD Thrombosis and Angiogenesis and Chemical Sciences, 65926 Frankfurt, Germany
Fax: +49(69)331399; e-Mail: armin.hofmeister@sanofi-aventis.com;
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Publication History

Received 23 December 2004
Publication Date:
19 April 2005 (online)

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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

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New address: S. Peukert, Novartis Institutes for Biomedical Research, 250 Massachusetts Avenue, Cambridge, MA 02139, USA; E-Mail: stefan.peukert@novartis.com.