URANOSYL]-3'-SPIRO-5''-(4''-AMINO-1'',2''-OXATHIOL 2'',2''-DIOXIDE) (TSAO) ANALOGS - SYNTHESIS AND ANTI-HIV-1 ACTIVITY

Several 4- or 5-monosubsituted and 4,5-disubstituted 1,2,3-triazole an alogues of the anti-HIV-1 lead com pound ]thymine]-3'-spiro-5''(4''-am ino-1'',2''-oxathiole 2'',2''-dioxide) (TSAO-T) have been prepared and evaluated as inhibitors of HIV-1-induced cytopathicity. These analogu es have been prepared by 1,3-diplar cycloaddition of silyl)-beta-D-rib ofuranosyl]-3-spiro-5'-(4'-amino- and and 4'-(N-acetylamino)1',2'-oxat hiole 2',2'-dioxide) (TSAO) azides to various substituted acetylenes. Several 4- and 5-substituted 1,2,3-triazole-TSAO analogues proved supe rior to the unsubstituted derivative by 1-2 orders of magnitude. In pa rticular 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 mu M). They show a similar resistance spectrum as previously noted for TSAO-T and relate d derivatives.