| 摘要: | 全球每年約有一千萬到一千五百萬人感染「腸病毒」(Enteroviruses)，而「腸病毒71型」(Enterovirus 71)是其中最具傳染性及致命性之病毒。台灣近二十年來爆發多次「腸病毒71型」感染，最嚴重的爆發為1998年的流行，13萬兒童得到「手足口病」、405名重症病患和78人死亡。然而對其病毒了解有限、無可使用之疫苗或專一性抗「腸病毒71型」藥物，使研發對抗「腸病毒71型」之新藥具有急迫的需要。
本實驗室以「阿昔洛韋」(Acyclovir)與「去甲替林」(Nortriptyline)做化學鍵之結合，所得分子經抗病毒測試後對「腸病毒71型」具有良好抑制的活性，但類似性質之「阿昔洛韋」與「金剛胺」(Amantadine)的共軛分子則不具有活性。據此本人改變「去甲替林」的分子結構，合成較少碳鏈之「去甲替林」、置換「脂芳烴」以增加平面性等方法，研究抗病毒活性與結構的關係，以利於未來開發出更具有抑制作用的抗「腸病毒71型」藥物。
其合成方法為將「芳烴胺」藉由「三光氣」反應成「異氰酸酯」，與含矽保護基阿昔洛韋進行加成反應，再去保護合成目標分子，並利用核磁共振光譜儀、傅立葉轉換紅外線光譜儀和高解析質譜儀鑑定其結構。
Up to 1,500,000 individuals worldwide are infected with enteroviruses annually. Of those enteroviruses, Enterovirus71 (EV71) has spread globally, as evidenced by its highly infectious and fatal nature. A dangerous outbreak of EV71 in Taiwan over the past two decades occurred in 1998, in which nearly 130,000 children were infected with hand-foot-and-mouth disease (HFMD)
405 experienced severe neurological complications
and 78 died. Unfortunately, no e?ective antiviral drug treat EV71 disease. The above situation highlights the urgency of developing antienteroviral agents.
Given the above predicament, our laboratory commits itself to developing antiviral drugs, with our results demonstrating that nortriptyline–acyclovir conjugate have high replication activity, based on test results of the anti-virus "EV71." However, a similar compound, amantadine–acyclovir conjugate has no activity. Therefore, in this study, the molecular structure in which nortriptyline carbon chain length is reduced and nortriptyline is replaced by " arene " to increase the flatness of structure in order to examine the structure that describes the antiviral activity relationship.
The synthesis involved reacting arene amines with triphosgene, allowing the functional group transfer from amine to isocyanate, then reacting with acyclovir analogous by addition reaction. The target structures were examined by nuclear magnetic resonance, FT–IR spectra, and high-resolution mass spectrometry. |
