C-3 位全卤代和 3-甲基取代的 5'-去氮-3-去氮杂丝氨酸霉素：合成与抗病毒活性。

C-3 halo and 3-methyl substituted 5'-nor-3-deazaaristeromycins: synthesis and antiviral properties.

机构信息

Molette Laboratory for Drug Discovery, Department of Chemistry and Biochemistry, Auburn University, Auburn, AL 36849-5312, United States.

出版信息

Bioorg Med Chem. 2013 Jan 1;21(1):359-64. doi: 10.1016/j.bmc.2012.09.051. Epub 2012 Oct 22.

DOI:10.1016/j.bmc.2012.09.051

PMID:23176752

Abstract

To expand on the antiviral properties of 5'-noraristeromycin, synthetic entry into 3-substituted 3-deaza-5'-noraristeromyin derivatives (i.e., bromo, 4; iodo, 5; chloro, 6; and, methyl, 7) has been accomplished from a common intermediate. An extensive antiviral analysis showed 7 to be basically inactive (except for weak effects against VSV) and there were no general trends among the halo compounds (except versus reovirus-1 and influenza B). Individually, compound 4 was most favorable towards HCMV, VZV, HBV, and VV; product 5 against HBV, VSV, VV, influenza B, HCMV, and measles; and, target 6 towards Punta Toro, VSV, measles, parainflucenza-3, influenza A (H5N1), and influenza B. The methyl target 7 was inactive in all viral assays.

摘要

为了扩展 5'-去氮阿糖肌苷的抗病毒特性，我们从一个共同的中间体合成了 3-取代的 3-去氮-5'-去氮阿糖肌苷衍生物（即溴代物 4、碘代物 5、氯代物 6 和甲基化物 7）。广泛的抗病毒分析表明 7 基本上没有活性（除了对 VSV 的微弱作用），卤代物之间也没有一般趋势（除了对呼肠孤病毒-1 和流感 B 之外）。单独来看，化合物 4 对 HCMV、VZV、HBV 和 VV 最有利；化合物 5 对 HBV、VSV、VV、流感 B、HCMV 和麻疹最有利；而靶标 6 对 Punta Toro、VSV、麻疹、副流感-3、甲型流感（H5N1）和流感 B 最有利。所有病毒检测中，甲基化靶标 7 均无活性。