C型肝炎病毒及屈公熱病毒為RNA病毒，皆對全球人類健康造成相當大的威脅。每年有超過四十萬人死於C型肝炎病毒造成之肝臟疾病．在過去兩年，美國食品藥物管理局通過了若干抗C型肝炎病毒用藥，但這些藥物不但要價不斐，且具低持續性病毒學反應(SVR)，加上其長時間之療程，與導致患者不適之副作用，使得持續發展新型Ｃ型肝炎抑制劑，依然是一重要課題。屈公熱是一種由新興病毒屈公病毒所引起的急性傳染病。「屈公」一詞來自非洲馬康德(Makonde)語，意思是「扭折者」，用於形容罹患此病之患者，因為關節劇烈疼痛，而造成肢體扭曲。目前對於屈公熱疾病仍無有效之疫苗及治療方法。
本論文中，我們設計合成一系列新型以甲硫連結之咪唑—香豆素共軛化合物。一系列咪唑—香豆素共軛化合物中，計有三個化合物對於C型肝炎病毒有極佳之EC50值(5.1~8.4 μM)且具高選擇性(SI大於20)。由此系列化合物抑制C型病毒之構效關係中可歸納出幾點變因，如咪唑結構上一號氮上的氫原子以及香豆素結構上的取代基(氯、氟、溴、甲基及甲氧基)等。
此外，為了對抗屈公熱病毒，我們設計並合成一系列之香豆素－鳥苷共軛化合物。利用甲硫基，在6,8-雙硫鳥苷之六號位置引入具不同取代基之3-氯甲基香豆素。另外，也在6,8-雙硫鳥苷之八號碳引入對照組配位基(如:甲基、芐基以及萘甲基)。此系列化合物之結構已由光譜鑑定，根據生物數據分析推導之構效關係(SAR)，香豆素部分為關鍵部分，其上如有甲氧基取代，具良好之抗病毒效果，於鳥苷部分，其羥基可提高化合物水溶度，增加其藥理適性。在一系列具抗屈公熱病毒活性之化合物中，其中三個化合物有良好之抑制效果，其EC50值為9.9~13.9 μM，而選擇性指數(SI)達9.37~21.7。

Hepatitis C virus and chikungunya virus fall into the category of RNA and emerging viruses respectively, which cause serious global health-care problems. More than 400,000 people die from liver diseases related to the hepatitis C virus each year. During the past two years, the U.S. Food and Drug Administration has approved a few drugs for hepatitis C diseace. These therapeutic treatments, however, are expensive and limited by the low sustained virologic response rate, the long duration of treatment, and adverse events. As an emerging disease, chikungunya fever causes a major medical problem nowadays. The term “chikungunya” is a Makonde word for “that which bends up”, which refers to the contorted posture of infected patients suffering from severe joint pain. Unfortunately, current treatments of CHIK fever are for symptoms with no effective licensed vaccine and drug.
In this thesis, we report a series of new conjugated compounds were synthesized by chemical methods from imidazole and coumarin derivatives with a –SCH2– linkage. 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.
Moreover, a series of coumarin–guanosine conjugated compounds were designed and synthesized as potential chikungunya virus inhibiting agents. They were obtained by coupling of 6,8-dithioguanosine at its C-6 position with 3-(chloromethyl)coumarin reagents bearing F, Cl, Br, Me, and OMe substituents through a –SCH2– joint. Meanwhile, an organic “dummy” ligand (e.g., methy, benzyl, and naphthylmethyl) or coumarinyl moiety was attached at the C-8 position. Their chemical structures were determined unambiguously by spectroscopic methods. Three of these new conjugates were found to inhibit CHIKV in Vero cells with significant potency (EC50 = 9.9–13.9 μM) and showed low toxicity (CC50 = 96.5–212 μM). Their selectivity index values were 9.37–21.7. By analysis of the data from the anti-viral assays, their structure–activity relationship was derived. It indicates that the coumarin moiety is essential and OMe group is the best for anti-viral activity, as well as the three hydroxyl groups are helpful for hydrophilicity.

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