Biomaterial Database

Phthalazinones. Part 1: The design and synthesis of a novel series of potent inhibitors of poly(ADP-ribose)polymerase. 2005

Vincent M Loh, and Xiao-ling Cockcroft, and Krystyna J Dillon, and Lesley Dixon, and Jan Drzewiecki, and Penny J Eversley, and Sylvie Gomez, and Janet Hoare, and Frank Kerrigan, and Ian T W Matthews, and Keith A Menear, and Niall M B Martin, and Roger F Newton, and Jane Paul, and Graeme C M Smith, and Julia Vile, and Alan J Whittle

KuDOS Horsham Ltd, 26 Foundry Lane, Horsham, West Sussex RH13 5PX, UK. vloh@kudospharma.co.uk

Screening of the Maybridge compound collection identified 4-arylphthalazinones as micromolar inhibitors of PARP-1 catalytic activity. Subsequent optimisation of both inhibitory activity and metabolic stability led to a novel series of meta-substituted 4-benzyl-2H-phthalazin-1-ones with low nanomolar, cellular activity as PARP-1 inhibitors and promising metabolic stability in vitro.

UI	MeSH Term	Description	Entries
D007094	Imides	Organic compounds containing two acyl groups bound to NITROGEN.	Imide
D007700	Kinetics	The rate dynamics in chemical or physical systems.
D008958	Models, Molecular	Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.	Molecular Models,Model, Molecular,Molecular Model
D010793	Phthalazines	Bicyclic heterocyclic compounds containing a BENZENE ring fused to PYRIDAZINE.
D004791	Enzyme Inhibitors	Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.	Enzyme Inhibitor,Inhibitor, Enzyme,Inhibitors, Enzyme
D000067856	Poly(ADP-ribose) Polymerase Inhibitors	Chemicals and drugs that inhibit the action of POLY(ADP-RIBOSE)POLYMERASES.	Inhibitors of Poly(ADP-ribose) Polymerase,PARP Inhibitor,Poly(ADP-Ribose) Polymerase Inhibitor,Poly(ADP-ribosylation) Inhibitor,Inhibitors of Poly(ADP-ribose) Polymerases,PARP Inhibitors,Poly(ADP-ribosylation) Inhibitors,Inhibitor, PARP,Inhibitors, PARP
D000071137	Poly (ADP-Ribose) Polymerase-1	A poly(ADP-ribose) polymerase that contains two ZINC FINGERS in its N-terminal DNA-binding region. It modifies NUCLEAR PROTEINS involved in chromatin architecture and BASE EXCISION REPAIR with POLY ADENOSINE DIPHOSPHATE RIBOSE.	NAD+ ADP-ribosyltransferase-1,PARP-1 Protein,PARP1 Protein,Poly (ADP-Ribose) Synthase-1,NAD+ ADP ribosyltransferase 1,PARP 1 Protein
D013329	Structure-Activity Relationship	The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups.	Relationship, Structure-Activity,Relationships, Structure-Activity,Structure Activity Relationship,Structure-Activity Relationships
D015195	Drug Design	The molecular designing of drugs for specific purposes (such as DNA-binding, enzyme inhibition, anti-cancer efficacy, etc.) based on knowledge of molecular properties such as activity of functional groups, molecular geometry, and electronic structure, and also on information cataloged on analogous molecules. Drug design is generally computer-assisted molecular modeling and does not include PHARMACOKINETICS, dosage analysis, or drug administration analysis.	Computer-Aided Drug Design,Computerized Drug Design,Drug Modeling,Pharmaceutical Design,Computer Aided Drug Design,Computer-Aided Drug Designs,Computerized Drug Designs,Design, Pharmaceutical,Drug Design, Computer-Aided,Drug Design, Computerized,Drug Designs,Drug Modelings,Pharmaceutical Designs
D015394	Molecular Structure	The location of the atoms, groups or ions relative to one another in a molecule, as well as the number, type and location of covalent bonds.	Structure, Molecular,Molecular Structures,Structures, Molecular