Identification of substituted pyrazolo[1,5-a]quinazolin-5(4H)-one as potent poly(ADP-ribose)polymerase-1 (PARP-1) inhibitors.
A novel series of pyrazolo[1,5-a]quinazolin-5(4H)-one derivatives proved to be a potent class of PARP-1 inhibitors. An extensive SAR around the 3-position of pyrazole in the scaffold led to the discovery of amides derivatives as low nanomolar PARP-1 inhibitors.
Orvieto
Federica
F
IRBM - Merck Research Laboratories Rome, Via Pontina km 30,600, Pomezia, 00040 Rome, Italy. federica_orvieto@merck.com
Branca
Danila
D
Giomini
Claudia
C
Jones
Philip
P
Koch
Uwe
U
Ontoria
Jesus M
JM
Palumbi
Maria Cecilia
MC
Rowley
Michael
M
Toniatti
Carlo
C
Muraglia
Ester
E
D000577:Amides / Q000737:chemistry; D002625:Chemistry, Organic / Q000379:methods; D002626:Chemistry, Pharmaceutical / Q000379:methods; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D006367:HeLa Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D008956:Models, Chemical; D015394:Molecular Structure; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D052999:Quinazolinones / Q000138:chemical synthesis / Q000494:pharmacology; D013329:Structure-Activity Relationship
D000577:Amides; D004791:Enzyme Inhibitors; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011720:Pyrazoles; D052999:Quinazolinones