title: Design and synthesis of a novel class of CK2 inhibitors: application of copper- and gold-catalysed cascade reactions for fused nitrogen heterocycles.
abstract: Two classes of fused nitrogen heterocycles were designed as CK2 inhibitor candidates on the basis of previous structure-activity relationship (SAR) studies. Various dipyrrolo[3,2-b:2',3'-e]pyridine and benzo[g]indazole derivatives were prepared using transition-metal-catalysed cascade and/or multicomponent reactions. Biological evaluation of these candidates revealed that benzo[g]indazole is a promising scaffold for potent CK2 inhibitors. The inhibitory activities on cell proliferation of these potent CK2 inhibitors are also presented.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Yamato
authors.initials: Y
authors.lastname: Suzuki
authors.forename: Shinya
authors.initials: S
authors.lastname: Oishi
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Takei
authors.forename: Misato
authors.initials: M
authors.lastname: Yasue
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Misu
authors.forename: Saori
authors.initials: S
authors.lastname: Naoe
authors.forename: Zengye
authors.initials: Z
authors.lastname: Hou
authors.forename: Tatsuhide
authors.initials: T
authors.lastname: Kure
authors.forename: Isao
authors.initials: I
authors.lastname: Nakanishi
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Ohno
authors.forename: Akira
authors.initials: A
authors.lastname: Hirasawa
authors.forename: Gozoh
authors.initials: G
authors.lastname: Tsujimoto
authors.forename: Nobutaka
authors.initials: N
authors.lastname: Fujii
mesh_terms: D047390:Casein Kinase II / Q000037:antagonists & inhibitors*; D002384:Catalysis; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003300:Copper / Q000737:chemistry*; D006046:Gold / Q000737:chemistry*; D006571:Heterocyclic Compounds / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D017672:Nitrogen Compounds / Q000737:chemistry* / Q000494:pharmacology; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D006571:Heterocyclic Compounds; D017672:Nitrogen Compounds; D047428:Protein Kinase Inhibitors; D006046:Gold; D003300:Copper; D047390:Casein Kinase II