title: Design and synthesis of indole, 2,3-dihydro-indole, and 3,4-dihydro-2H-quinoline-1-carbothioic acid amide derivatives as novel HCV inhibitors.
abstract: An efficient synthetic methodology to provide indole, 2,3-dihydro-indole, and 3,4-dihydro-2H-quinoline-1-carbothioic acid amide derivatives is described. These conformationally restricted heterobicyclic scaffolds were evaluated as a novel class of HCV inhibitors. Introduction of an acyl group at the NH(2) of the thiourea moiety has been found to enhance inhibitory activity. The chain length and the position of the alkyl group on the indoline aromatic ring markedly influenced anti-HCV activity. The indoline scaffold was more potent than the corresponding indole and tetrahydroquinoline scaffolds and analogue 31 displayed excellent activity (EC(50)=510nM) against HCV without significant cytotoxicity (CC(50) >50microM).
authors.affiliation: Division of Biotechnology and Pharmaceutical Research, National Health Research Institutes, No. 35, Keyan Road, Zhunan Town, Miaoli County 350, Taiwan, ROC.
authors.forename: Iou-Jiun
authors.initials: IJ
authors.lastname: Kang
authors.forename: Li-Wen
authors.initials: LW
authors.lastname: Wang
authors.forename: Sheng-Ju
authors.initials: SJ
authors.lastname: Hsu
authors.forename: Chung-Chi
authors.initials: CC
authors.lastname: Lee
authors.forename: Yen-Chun
authors.initials: YC
authors.lastname: Lee
authors.forename: Yen-Shian
authors.initials: YS
authors.lastname: Wu
authors.forename: Tsu-An
authors.initials: TA
authors.lastname: Hsu
authors.forename: Andrew
authors.initials: A
authors.lastname: Yueh
authors.forename: Yu-Sheng
authors.initials: YS
authors.lastname: Chao
authors.forename: Jyh-Haur
authors.initials: JH
authors.lastname: Chern
mesh_terms: D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D045744:Cell Line, Tumor; D002626:Chemistry, Pharmaceutical / Q000379:methods; D015195:Drug Design; D016174:Hepacivirus / Q000378:metabolism*; D006526:Hepatitis C / Q000188:drug therapy*; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis* / Q000494:pharmacology; D008956:Models, Chemical; D008968:Molecular Conformation; D015394:Molecular Structure; D017434:Protein Structure, Tertiary; D011804:Quinolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D017361:Viral Nonstructural Proteins / Q000737:chemistry
chemical_list: D000998:Antiviral Agents; D007211:Indoles; D011804:Quinolines; D017361:Viral Nonstructural Proteins