Structure−Activity Relationship of New Anti-Hepatitis C Virus Agents: Heterobicycle−Coumarin Conjugates
Johan NeytsRega Institute for Medical Research, Katholieke Universiteit Leuven, Minderbroedersstraat 10, B-3000 Leuven, Belgium, Department of Chemistry, National Tsing Hua University, Hsinchu, Taiwan 30013, R.O.C., Department of Chemistry, National Central University, Jhongli City, Taiwan 32001, R.O.CErik De ClercqRega Institute for Medical Research, Katholieke Universiteit Leuven, Minderbroedersstraat 10, B-3000 Leuven, Belgium, Department of Chemistry, National Tsing Hua University, Hsinchu, Taiwan 30013, R.O.C., Department of Chemistry, National Central University, Jhongli City, Taiwan 32001, R.O.CRaghunath SinghaRega Institute for Medical Research, Katholieke Universiteit Leuven, Minderbroedersstraat 10, B-3000 Leuven, Belgium, Department of Chemistry, National Tsing Hua University, Hsinchu, Taiwan 30013, R.O.C., Department of Chemistry, National Central University, Jhongli City, Taiwan 32001, R.O.CYung ChangRega Institute for Medical Research, Katholieke Universiteit Leuven, Minderbroedersstraat 10, B-3000 Leuven, Belgium, Department of Chemistry, National Tsing Hua University, Hsinchu, Taiwan 30013, R.O.C., Department of Chemistry, National Central University, Jhongli City, Taiwan 32001, R.O.CAsish R. DasRega Institute for Medical Research, Katholieke Universiteit Leuven, Minderbroedersstraat 10, B-3000 Leuven, Belgium, Department of Chemistry, National Tsing Hua University, Hsinchu, Taiwan 30013, R.O.C., Department of Chemistry, National Central University, Jhongli City, Taiwan 32001, R.O.CSubhasish ChakrabortyRega Institute for Medical Research, Katholieke Universiteit Leuven, Minderbroedersstraat 10, B-3000 Leuven, Belgium, Department of Chemistry, National Tsing Hua University, Hsinchu, Taiwan 30013, R.O.C., Department of Chemistry, National Central University, Jhongli City, Taiwan 32001, R.O.CShih Ching HongRega Institute for Medical Research, Katholieke Universiteit Leuven, Minderbroedersstraat 10, B-3000 Leuven, Belgium, Department of Chemistry, National Tsing Hua University, Hsinchu, Taiwan 30013, R.O.C., Department of Chemistry, National Central University, Jhongli City, Taiwan 32001, R.O.CShwu‐Chen TsayRega Institute for Medical Research, Katholieke Universiteit Leuven, Minderbroedersstraat 10, B-3000 Leuven, Belgium, Department of Chemistry, National Tsing Hua University, Hsinchu, Taiwan 30013, R.O.C., Department of Chemistry, National Central University, Jhongli City, Taiwan 32001, R.O.CMing‐Hua HsuRega Institute for Medical Research, Katholieke Universiteit Leuven, Minderbroedersstraat 10, B-3000 Leuven, Belgium, Department of Chemistry, National Tsing Hua University, Hsinchu, Taiwan 30013, R.O.C., Department of Chemistry, National Central University, Jhongli City, Taiwan 32001, R.O.CJih Ru HwuRega Institute for Medical Research, Katholieke Universiteit Leuven, Minderbroedersstraat 10, B-3000 Leuven, Belgium, Department of Chemistry, National Tsing Hua University, Hsinchu, Taiwan 30013, R.O.C., Department of Chemistry, National Central University, Jhongli City, Taiwan 32001, R.O.C
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Аннотация
For establishment of the structure-activity relationship, 19 heterobicycle-coumarin conjugated compounds with the -SCH(2)- linker were synthesized and found to possess significant antiviral activities. Prominent examples included imidazopyridine-coumarin 12c, purine-coumarin 12d, and benzoxazole-coumarin 14c, which inhibited HCV replication at an EC(50) of 6.8, 2.0, and 12 microM, respectively. The heteroatoms in bicycles and the substituent effect on coumarin played essential roles.
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