title: Synthesis and Structure-Activity Relationships of Imidazole-Coumarin Conjugates against Hepatitis C Virus.
abstract: A series of new conjugated compounds with a -SCH₂- linkage were synthesized by chemical methods from imidazole and coumarin derivatives. The experimental results indicate that of the twenty newly synthesized imidazole-coumarin conjugates, three of them exhibited appealing EC50 values (5.1-8.4 μM) and selective indices >20 against hepatitis C virus. Their potency and selectivity were increased substantially by modification of their structure with two factors: imidazole nucleus with a hydrogen atom at the N(1) position and coumarin nucleus with a substituent, such as Cl, F, Br, Me, and OMe. These guidelines provide valuable information for further development of conjugated compounds as anti-viral agents.
authors.affiliation: Department of Chemistry &amp; Frontier Research Center on Fundamental and Applied Sciences of Matters, National Tsing Hua University, Hsinchu 30013, Taiwan. tsay.susan@gmail.com.|Department of Chemistry, National Central University, Jhongli District, Taoyuan City 32001, Taiwan. tsay.susan@gmail.com.
authors.forename: Shwu-Chen
authors.initials: SC
authors.lastname: Tsay
authors.affiliation: Department of Chemistry &amp; Frontier Research Center on Fundamental and Applied Sciences of Matters, National Tsing Hua University, Hsinchu 30013, Taiwan. kchlsu@mail2000.com.tw.
authors.forename: Shu-Yu
authors.initials: SY
authors.lastname: Lin
authors.affiliation: Department of Chemistry &amp; Frontier Research Center on Fundamental and Applied Sciences of Matters, National Tsing Hua University, Hsinchu 30013, Taiwan. jordanback2001@yahoo.com.tw.
authors.forename: Wen-Chieh
authors.initials: WC
authors.lastname: Huang
authors.affiliation: Department of Chemistry &amp; Frontier Research Center on Fundamental and Applied Sciences of Matters, National Tsing Hua University, Hsinchu 30013, Taiwan. minghua.hsu@gmail.com.
authors.forename: Ming-Hua
authors.initials: MH
authors.lastname: Hsu
authors.affiliation: Department of Chemistry &amp; Frontier Research Center on Fundamental and Applied Sciences of Matters, National Tsing Hua University, Hsinchu 30013, Taiwan. kchwang@mx.nthu.edu.tw.
authors.forename: Kuo Chu
authors.initials: KC
authors.lastname: Hwang
authors.affiliation: Department of Chemistry &amp; Frontier Research Center on Fundamental and Applied Sciences of Matters, National Tsing Hua University, Hsinchu 30013, Taiwan. cclin66@mx.nthu.edu.tw.
authors.forename: Chun-Cheng
authors.initials: CC
authors.lastname: Lin
authors.affiliation: Department of Chemistry &amp; Frontier Research Center on Fundamental and Applied Sciences of Matters, National Tsing Hua University, Hsinchu 30013, Taiwan. jchorng@mx.nthu.edu.tw.
authors.forename: Jia-Cherng
authors.initials: JC
authors.lastname: Horng
authors.affiliation: Department of Chemistry &amp; Frontier Research Center on Fundamental and Applied Sciences of Matters, National Tsing Hua University, Hsinchu 30013, Taiwan. icchen@mx.nthu.edu.tw.
authors.forename: I-Chia
authors.initials: IC
authors.lastname: Chen
authors.affiliation: Department of Chemistry &amp; Frontier Research Center on Fundamental and Applied Sciences of Matters, National Tsing Hua University, Hsinchu 30013, Taiwan. jrhwu@mx.nthu.edu.tw.|Department of Chemistry, National Central University, Jhongli District, Taoyuan City 32001, Taiwan. jrhwu@mx.nthu.edu.tw.
authors.forename: Jih Ru
authors.initials: JR
authors.lastname: Hwu
authors.affiliation: Department of Chemistry, National Central University, Jhongli District, Taoyuan City 32001, Taiwan. fshieh@ncu.edu.tw.
authors.forename: Fa-Kuen
authors.initials: FK
authors.lastname: Shieh
authors.affiliation: Rega Institute for Medical Research, Katholieke Universiteit Leuven, Minderbroedersstraat 10, Leuven B-3000, Belgium. pieter.leyssen@rega.kuleuven.be.
authors.forename: Pieter
authors.initials: P
authors.lastname: Leyssen
authors.affiliation: Rega Institute for Medical Research, Katholieke Universiteit Leuven, Minderbroedersstraat 10, Leuven B-3000, Belgium. johan.neyts@rega.kuleuven.be.
authors.forename: Johan
authors.initials: J
authors.lastname: Neyts
mesh_terms: D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D003374:Coumarins / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D016174:Hepacivirus / Q000187:drug effects* / Q000502:physiology; D007093:Imidazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D003374:Coumarins; D007093:Imidazoles
keywords: coumarin; hepatitis C virus; imidazole; nitrogen heterocycles; structure–activity relationships