title: Quinoxalin-2(1H)-one derivatives as inhibitors against hepatitis C virus.
abstract: Hepatitis C virus (HCV) infection is a serious problem worldwide, but no effective drugs are currently available. Through screening of our privileged structure library, quinoxalin-2(1H)-one derivative N-(7-(cyclohexyl(methyl)amino)-3-oxo-3,4-dihydroquinoxalin-6-ylcarbamothioyl)benzamide (compound 1) was identified as potent HCV inhibitor in vitro. Subsequently, a structure-activity relationship analysis was carried out that showed N-(7-(cyclohexyl(methyl)amino)-3-oxo-3,4-dihydroquinoxalin-6-ylcarbamothioyl)furan-2-carboxamide (compound 11, EC(50)=1.8 μM, SI=9.6), 6-(cyclohexyl(methyl)amino)-7-(4-phenylthiazol-2-ylamino)quinoxalin-2(1H)-one (compound 33, EC(50)=1.67 μM, SI=37.4), 2-(cyclohexyl(methyl)amino)-3-(4-phenylthiazol-2-ylamino)-7,8,9,10-tetrahydro-5H-pyrido[1,2-a]quinoxalin-6(6aH)-one (compound 60, EC(50)=1.19 μM, SI=9.27), 8-(cyclohexyl(methyl)amino)-7-(4-phenylthiazol-2-ylamino)pyrrolo[1,2-a]quinoxalin-4(5H)-one (compound 65, EC(50)=1.82 μM, SI=9.9), and 6-(diethylamino)-7-(4-phenylthiazol-2-ylamino)quinoxalin-2(1H)-one (compound 78, EC(50)=1.27 μM, SI=17.9) acted against HCV. The data from the structure-activity relationship study suggests that quinoxalin-2(1H)-one derivatives exhibited potent activity against HCV.
authors.affiliation: Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, 2A Nanwei Road, Xicheng District, Beijing 100050, PR China.
authors.forename: Rui
authors.initials: R
authors.lastname: Liu
authors.forename: Zhuhui
authors.initials: Z
authors.lastname: Huang
authors.forename: Michael G
authors.initials: MG
authors.lastname: Murray
authors.forename: Xiaoyong
authors.initials: X
authors.lastname: Guo
authors.forename: Gang
authors.initials: G
authors.lastname: Liu
mesh_terms: D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D016174:Hepacivirus / Q000187:drug effects*; D006801:Humans; D008956:Models, Chemical; D008958:Models, Molecular; D015394:Molecular Structure; D011810:Quinoxalines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D011810:Quinoxalines