title: Synthesis and SAR of novel tricyclic quinoxalinone inhibitors of poly(ADP-ribose)polymerase-1 (PARP-1).
abstract: Based on screening hit 1, a series of tricyclic quinoxalinones have been designed and evaluated for inhibition of PARP-1. Substitutions at the 7- and 8-positions of the quinoxalinone ring led to a number of compounds with good enzymatic and cellular potency. The tricyclic quinoxalinone class is sensitive to modifications of both the amine substituent and the tricyclic core. The synthesis and structure-activity relationship studies are presented.
authors: Cancer Research, GPRD, Abbott Laboratories, 100 Abbott Park Rd., Abbott Park, IL 60064, USA. julie.miyashiro@abbott.com
authors: Julie
authors: J
authors: Miyashiro
authors: Keith W
authors: KW
authors: Woods
authors: Chang H
authors: CH
authors: Park
authors: Xuesong
authors: X
authors: Liu
authors: Yan
authors: Y
authors: Shi
authors: Eric F
authors: EF
authors: Johnson
authors: Jennifer J
authors: JJ
authors: Bouska
authors: Amanda M
authors: AM
authors: Olson
authors: Yan
authors: Y
authors: Luo
authors: Elizabeth H
authors: EH
authors: Fry
authors: Vincent L
authors: VL
authors: Giranda
authors: Thomas D
authors: TD
authors: Penning
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology; D017209:Apoptosis; D002467:Cell Nucleus / Q000378:metabolism; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D004260:DNA Repair; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007700:Kinetics; D008958:Models, Molecular; D008968:Molecular Conformation; D009536:Niacinamide / Q000737:chemistry; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011810:Quinoxalines / Q000138:chemical synthesis* / Q000737:chemistry*; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011810:Quinoxalines; D009536:Niacinamide