Identification of ring-fused pyrazolo pyridin-2-ones as novel poly(ADP-ribose)polymerase-1 inhibitors.
A novel class of PARP-1 inhibitors was identified containing a non-aromatic heterocycle or carbocycle fused to a pyrazolo pyridin-2-one. Compounds displayed low nanomolar binding activity in the PARP-1 binding assay and submicromolar activity in a cell based chemosensitization assay.
Moree
Wilna J
WJ
Deltagen Research Laboratories (Former CombiChem, Inc.), 4570 Executive Drive, Suite 400, San Diego, CA 92121, USA. wmoree@neurocrine.com
Goldman
Phyllis
P
Demaggio
Anthony J
AJ
Christenson
Erik
E
Herendeen
Dan
D
Eksterowicz
John
J
Kesicki
Edward A
EA
McElligott
David L
DL
Beaton
Graham
G
D000818:Animals; D002645:Chickens; D020650:Combinatorial Chemistry Techniques; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D015394:Molecular Structure; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011720:Pyrazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D011728:Pyridones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship
D004791:Enzyme Inhibitors; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011720:Pyrazoles; D011728:Pyridones