title: Novel alkoxybenzamide inhibitors of poly(ADP-ribose) polymerase.
abstract: We have previously described poly(ADP-ribose) polymerase-1 (PARP-1) inhibitors based on a substituted benzyl-phthalazinone scaffold. As an alternative chemical template, a novel series of alkoxybenzamides were developed with restricted conformation through intramolecular hydrogen bond formation; the compounds exhibit low nM enzyme and cellular activity as PARP-1 inhibitors.
authors.affiliation: KuDOS Pharmaceuticals Ltd, 410 Cambridge Science Park, Milton Road, Cambridge CB4 0PE, UK. kmenear@kudospharma.co.uk
authors.forename: Keith A
authors.initials: KA
authors.lastname: Menear
authors.forename: Claire
authors.initials: C
authors.lastname: Adcock
authors.forename: Francisco Cuenca
authors.initials: FC
authors.lastname: Alonso
authors.forename: Kristel
authors.initials: K
authors.lastname: Blackburn
authors.forename: Louise
authors.initials: L
authors.lastname: Copsey
authors.forename: Jan
authors.initials: J
authors.lastname: Drzewiecki
authors.forename: Alexandra
authors.initials: A
authors.lastname: Fundo
authors.forename: Armelle
authors.initials: A
authors.lastname: Le Gall
authors.forename: Sylvie
authors.initials: S
authors.lastname: Gomez
authors.forename: Hashim
authors.initials: H
authors.lastname: Javaid
authors.forename: Carlos Fenandez
authors.initials: CF
authors.lastname: Lence
authors.forename: Niall M B
authors.initials: NM
authors.lastname: Martin
authors.forename: Chris
authors.initials: C
authors.lastname: Mydlowski
authors.forename: Graeme C M
authors.initials: GC
authors.lastname: Smith
mesh_terms: D002626:Chemistry, Pharmaceutical; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D006367:HeLa Cells; D006801:Humans; D006860:Hydrogen Bonding; D020128:Inhibitory Concentration 50; D008956:Models, Chemical; D008968:Molecular Conformation; D015394:Molecular Structure; D000071137:Poly (ADP-Ribose) Polymerase-1; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011065:Poly(ADP-ribose) Polymerases / Q000737:chemistry; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
chemical_list: D004791:Enzyme Inhibitors; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; C499320:PARP1 protein, human; C483041:PARP2 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases