Alvarez R, Velázquez S, San-Félix A, Aquaro S, De Clercq E, Perno C F, Karlsson A, Balzarini J, Camarasa M J
Instituto de Química Médica (C.S.I.C.), Madrid, Spain.
J Med Chem. 1994 Nov 25;37(24):4185-94. doi: 10.1021/jm00050a015.
Several 4- or 5-monosubsituted and 4,5-disubstituted 1,2,3-triazole analogues of the anti-HIV-1 lead compound [1-[2',5'-bis-O-(tert-butyldimethylsilyl)-beta-D- ribofuranosyl]thymine]-3'-spiro-5"-(4"-amino-1",2"-oxathiole 2",2"-dioxide) (TSAO-T) have been prepared and evaluated as inhibitors of HIV-1-induced cytopathicity. These analogues have been prepared by 1,3-diplar cycloaddition of [2,5-bis-O-(tert-butyldimethylsilyl)-beta-D-ribofuranosyl]- 3-spiro-5'-(4'-amino- and 4'-(N-acetylamino)-1',2'-oxathiole 2',2'-dioxide) (TSAO) azides to various substituted acetylenes. Several 4- and 5-substituted 1,2,3-triazole-TSAO analogues proved superior to the unsubstituted derivative by 1-2 orders of magnitude. In particular the 5-substituted amido-, (methylamido)-, and (dimethylamido)-1,2,3-triazole derivatives of TSAO were endowed with potent anti-HIV-1 activity (50% effective concentration: 0.056-0.52 microM). They show a similar resistance spectrum as previously noted for TSAO-T and related derivatives.
已制备了抗HIV-1先导化合物[1-[2',5'-双-O-(叔丁基二甲基甲硅烷基)-β-D-呋喃核糖基]胸腺嘧啶]-3'-螺-5"-(4"-氨基-1",2"-氧硫杂环戊烷2",2"-二氧化物)(TSAO-T)的几种4-或5-单取代以及4,5-二取代的1,2,3-三唑类似物，并将其作为HIV-1诱导的细胞病变的抑制剂进行了评估。这些类似物是通过[2,5-双-O-(叔丁基二甲基甲硅烷基)-β-D-呋喃核糖基]-3-螺-5'-(4'-氨基-和4'-(N-乙酰氨基)-1',2'-氧硫杂环戊烷2',2'-二氧化物)(TSAO)叠氮化物与各种取代乙炔的1,3-偶极环加成反应制备的。几种4-和5-取代的1,2,3-三唑-TSAO类似物被证明比未取代的衍生物优越1至2个数量级。特别是TSAO的5-取代酰胺基、(甲基酰胺基)-和(二甲基酰胺基)-1,2,3-三唑衍生物具有强大的抗HIV-1活性(50%有效浓度：0.056 - 0.52 microM)。它们显示出与先前报道的TSAO-T及相关衍生物相似的耐药谱。
