The hydroxy metabolites of rimantadine (3-5) were synthesized and compared to amantadine (1) and rimantadine (2) for their ability to inhibit the replication of influenza viruses in vitro. All three metabolites were inhibitory to wild-type influenza A viruses (H3N2 and H1N1). In particular, 2-hydroxyrimantadine (3) showed similar activity to amantadine, but the 3- and 4-hydroxy metabolites (4 and 5, respectively), both of which are found in rimantadine-treated patients, showed only modest inhibitory activity. A rimantadine-resistant isolate of influenza A virus exhibited cross-resistance to amantadine and to each of the metabolites 3-5. None of the compounds were effective against influenza B virus.

中文翻译：

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金刚烷胺代谢产物的合成及其抗病毒活性。

合成金刚烷胺（3-5）的羟基代谢物，并将其与金刚烷胺（1）和金刚乙胺（2）的体外抑制流感病毒复制的能力进行比较。所有这三种代谢物均抑制野生型A型流感病毒（H3N2和H1N1）。特别是2-羟基金刚烷胺（3）显示出与金刚烷胺相似的活性，但是在金刚烷胺治疗的患者中发现的3-羟基和4-羟基代谢物（分别为4和5）仅表现出适度的抑制活性。耐金刚烷胺的甲型流感病毒分离株对金刚烷胺和每个代谢物3-5具有交叉耐药性。这些化合物均不能有效抵抗乙型流感病毒。