title: 4-(Aminoalkylamino)-3-benzimidazole-quinolinones as potent CHK-1 inhibitors.
abstract: CHK-1 is one of the key enzymes regulating checkpoints in cellular growth cycles. Novel 4-(amino-alkylamino)-3-benzimidazole-quinolinones were prepared and assayed for their ability to inhibit CHK-1. These compounds are potent cell permeable CHK-1 inhibitors and showed synergistic effect with a DNA-damaging agent, camptothecin.
authors.affiliation: Chiron Corporation, 4560 Horton Street, Emeryville, CA 94608, USA. zhi-jie_ni@chiron.com
authors.forename: Zhi-Jie
authors.initials: ZJ
authors.lastname: Ni
authors.forename: Paul
authors.initials: P
authors.lastname: Barsanti
authors.forename: Nathan
authors.initials: N
authors.lastname: Brammeier
authors.forename: Anthony
authors.initials: A
authors.lastname: Diebes
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Poon
authors.forename: Simon
authors.initials: S
authors.lastname: Ng
authors.forename: Sabina
authors.initials: S
authors.lastname: Pecchi
authors.forename: Keith
authors.initials: K
authors.lastname: Pfister
authors.forename: Paul A
authors.initials: PA
authors.lastname: Renhowe
authors.forename: Savithri
authors.initials: S
authors.lastname: Ramurthy
authors.forename: Allan S
authors.initials: AS
authors.lastname: Wagman
authors.forename: Dirksen E
authors.initials: DE
authors.lastname: Bussiere
authors.forename: Vincent
authors.initials: V
authors.lastname: Le
authors.forename: Yasheen
authors.initials: Y
authors.lastname: Zhou
authors.forename: Johanna M
authors.initials: JM
authors.lastname: Jansen
authors.forename: Sylvia
authors.initials: S
authors.lastname: Ma
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Gesner
mesh_terms: D000478:Alkylation; D000586:Amination; D001562:Benzimidazoles / Q000737:chemistry*; D045744:Cell Line, Tumor; D000071877:Checkpoint Kinase 1; D018360:Crystallography, X-Ray; D006801:Humans; D020128:Inhibitory Concentration 50; D008958:Models, Molecular; D015394:Molecular Structure; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D011494:Protein Kinases / Q000737:chemistry / Q000378:metabolism*; D015363:Quinolones / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D001562:Benzimidazoles; D047428:Protein Kinase Inhibitors; D015363:Quinolones; C031000:benzimidazole; D011494:Protein Kinases; D000071877:Checkpoint Kinase 1