title: Identification of substituted pyrazolo[1,5-a]quinazolin-5(4H)-one as potent poly(ADP-ribose)polymerase-1 (PARP-1) inhibitors.
abstract: 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.
authors.affiliation: IRBM - Merck Research Laboratories Rome, Via Pontina km 30,600, Pomezia, 00040 Rome, Italy. federica_orvieto@merck.com
authors.forename: Federica
authors.initials: F
authors.lastname: Orvieto
authors.forename: Danila
authors.initials: D
authors.lastname: Branca
authors.forename: Claudia
authors.initials: C
authors.lastname: Giomini
authors.forename: Philip
authors.initials: P
authors.lastname: Jones
authors.forename: Uwe
authors.initials: U
authors.lastname: Koch
authors.forename: Jesus M
authors.initials: JM
authors.lastname: Ontoria
authors.forename: Maria Cecilia
authors.initials: MC
authors.lastname: Palumbi
authors.forename: Michael
authors.initials: M
authors.lastname: Rowley
authors.forename: Carlo
authors.initials: C
authors.lastname: Toniatti
authors.forename: Ester
authors.initials: E
authors.lastname: Muraglia
mesh_terms: 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
chemical_list: D000577:Amides; D004791:Enzyme Inhibitors; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011720:Pyrazoles; D052999:Quinazolinones