Novel alkoxybenzamide inhibitors of poly(ADP-ribose) polymerase.
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.
Menear
Keith A
KA
KuDOS Pharmaceuticals Ltd, 410 Cambridge Science Park, Milton Road, Cambridge CB4 0PE, UK. kmenear@kudospharma.co.uk
Adcock
Claire
C
Alonso
Francisco Cuenca
FC
Blackburn
Kristel
K
Copsey
Louise
L
Drzewiecki
Jan
J
Fundo
Alexandra
A
Le Gall
Armelle
A
Gomez
Sylvie
S
Javaid
Hashim
H
Lence
Carlos Fenandez
CF
Martin
Niall M B
NM
Mydlowski
Chris
C
Smith
Graeme C M
GC
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
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