CYCLOPENTENYL NUCLEOSIDE ISOSTERES AS POTENTIAL ANTITUMOR AND ANTIVIRAL AGENTS

这项工作继续产生一系列新的环戊烯基(CPE) 核苷异构体正在被研究为抗肿瘤或 抗病毒药物。令人惊叹的抗肿瘤药物和 胞嘧啶类似物(CPE-C)的抗病毒活性 对这类碳环化合物的广泛研究 核苷。在这一努力中，新的改进方法 合成和保护-解除保护程序 了解并适应CPE系列的化学成分。 合成了CPE-C的Ara和2‘-脱氧类似物。ARA-CPE- C对A2型流感病毒有活性，但两种化合物都不是 具有抗肿瘤活性。CPE-U的额外数量是 用于体内研究的嘧啶类化合物的合成 打捞路径。CPE-C的活性代谢产物(其5‘- 三磷酸盐)也被合成，并被鉴定为有效的 胞苷三磷酸合成酶的抑制剂。 在环戊烯基嘌呤类化合物中，3-去氮杂环素，a S的强效抑制剂--腺苷同型半胱氨酸水解酶，具有优异的 对RNA和DNA病毒的抗病毒活性 高水平的细胞毒性通常与亲本有关 发酵产物奈普洛星。

This work continues to generate a series of new cyclopentenyl (CPE) nucleoside isosteres that are being studied as antitumor or antiviral agents. The discovery of the remarkable antitumor and antiviral activity of the cytosine analogue (CPE-C) has prompted an extensive investigation into this type of carbocyclic nucleoside. During this endeavor, new improved methods of synthesis and protection-deprotection procedures have been investigated and adapted to the chemistry of the CPE series. The ara and 2'-deoxy analogues of CPE-C were synthesized. Ara-CPE- C is active against the Influenza A2 virus, but neither compound has antitumor activity. Additional amounts of CPE-U were synthesized for in vivo studies of the inhibition of the pyrimidine salvage pathway. The active metabolite of CPE-C (its 5'- triphosphate) also was synthesized and identified as a potent inhibitor of cytidine triphosphate synthetase. Among the cyclopentenyl purine compounds, 3-deazaneplanocin, a potent inhibitor of S-adenosylhomocysteine hydrolase, has excellent antiviral activity against both RNA and DNA viruses without the high level of cytotoxicity normally associated with the parent fermentation product, neplanocin.