title: Synthesis and biological evaluation of 3-(4-substituted-phenyl)-N-hydroxy-2-propenamides, a new class of histone deacetylase inhibitors.
abstract: Inhibitors of histone deacetylases (HDACs) have been shown to induce differentiation and/or apoptosis of human tumor cells. Novel 3-(4-substituted-phenyl)-N-hydroxy-2-propenamides have been prepared as a new class of HDAC inhibitors and evaluated for their antiproliferative activity and HDAC inhibitory activity. Incorporation of a 1,4-phenylene carboxamide linker, shown by 5, and a 4-(dimethylamino)phenyl or 4-(pyrrolidin-1-yl)phenyl group as a cap substructure generated highly potent hydroxamic acid-based HDAC inhibitors 5a and 5b.
authors.affiliation: In2Gen Co. Ltd., 28 Yongon-dong, Chongno-gu, Seoul 110-799, Korea. dkkim@ewha.ac.kr
authors.forename: Dae-Kee
authors.initials: DK
authors.lastname: Kim
authors.forename: Ju Young
authors.initials: JY
authors.lastname: Lee
authors.forename: Jae-Sun
authors.initials: JS
authors.lastname: Kim
authors.forename: Je-Ho
authors.initials: JH
authors.lastname: Ryu
authors.forename: Jin-Young
authors.initials: JY
authors.lastname: Choi
authors.forename: Jun Won
authors.initials: JW
authors.lastname: Lee
authors.forename: Guang-Jin
authors.initials: GJ
authors.lastname: Im
authors.forename: Tae-Kon
authors.initials: TK
authors.lastname: Kim
authors.forename: Jung Woo
authors.initials: JW
authors.lastname: Seo
authors.forename: Hyun-Ju
authors.initials: HJ
authors.lastname: Park
authors.forename: Jakyung
authors.initials: J
authors.lastname: Yoo
authors.forename: Jung-Hyun
authors.initials: JH
authors.lastname: Park
authors.forename: Tae-You
authors.initials: TY
authors.lastname: Kim
authors.forename: Yung-Jue
authors.initials: YJ
authors.lastname: Bang
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001549:Benzamides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001665:Binding Sites; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D056572:Histone Deacetylase Inhibitors; D006801:Humans; D006877:Hydroxamic Acids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D008958:Models, Molecular; D011485:Protein Binding; D013329:Structure-Activity Relationship
chemical_list: C480612:4-dimethylamino-N-(4-(2-hydroxycarbamoylvinyl)benzyl)benzamide; D000970:Antineoplastic Agents; D001549:Benzamides; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; C480613:N-(4-(2-hydroxycarbamoylvinyl)benzyl)-4-pyrrolidin-1-ylbenzamide