蛋白質酵素抑制劑作為抗愛滋病毒藥物之研究進展

Recent Development of Protease Inhibitors as Anti-HIV Agents

楊志平(Chih-Ping Yang)

《化學》 52卷3期 (1994/09) Pp. 336-344

https://doi.org/10.6623/chem.1994044

摘要

愛滋病(AIDS)是由人類後天免疫缺乏病毒(Human Immunodeficiency Virus, HIV)所引起的世紀黑死病，目前全球已有超過一千七百萬人感染了這一個疾病。由於世界上各大藥廠的醫藥科學家積極研究，已有一些可暫時抑制愛滋病毒複製的藥物，如反轉錄酵素抑制劑。然而愛滋病毒對於此一類發物產生抗藥性的問題，是一個長久困擾愛滋病也床治療而無法解決的難題。蛋白質酵素是愛滋病毒複製過程中的一個必需酵素，因此使用蛋白質酵素制劑來治療愛滋病，成為一個非常吸引人的研究方向。由於此類藥物的研究是近年來世界上各大藥廠的熱門研究方向，本文將僅就其中較有開創性的藥物設計，以及三個已經進入人體臨床試驗的藥物，作一簡略的介紹。

並列摘要

There are 17 million people in the world infected with HIV up-to-date. Most of them will develop AIDS symptom within a few years and die in a couple years due to lack of effective medical treatment. There are only three drugs, AZT, ddI, ddC, currently used in clinical practice. These drugs are very potent reverse transcriptase inhibitors. However, the drug-resistant strain of HIV can be developed in patients within a few weeks after the treatment with these uncleoside analogues. HIV protease is also an essential enzyme for the replication of HIV in human lymphocytes. Thus, design, synthesis and biological evaluation of novel protease inhibitors as potential therapeutical agents for the treatment of HIV infection become an attractive and fast-growing research area. Since there are thousands of publications dealing with HIV protease inhibitors, this review will only concentrate on the drug design strategy and their biological activities. Three drug candidates, L-735,524, A-77,003 and U96,988, entered human clinical trials will be used as successful examples.