Regiospecific synthesis and anti-human immunodeficiency virus activity of novel 5-substituted N-alkylcarbamoyl and N,N-dialkyl carbamoyl 1,2,3-triazole-TSAO analogues

Several 5-N-alkyl and 5-N,N-dialkylcarbamoyl substituted analogues of the a nti-human immunodeficiency virus (HIV) type 1 lead compound[1-[2',5'-bis-O- (tert-butyldimethytsilyl)-beta-D-ribofuranosyl] -5-(N,N-dimethylcarbamoyl)- 1,2,3-triazole]-3'-spiro-5"-(4"-amino-1",2"-oxathiole-2",2"dioxide) have be en prepared and evaluated as inhibitors of HIV-1 replication. A new regiosp ecific synthetic procedure is described. The compounds were prepared by cyc loaddition of the appropriate glycosylazide to 2-oxoalkylidentriphenyl-phos phoranes, followed by treatment with primary or secondary amines, to yield, exclusively, 5-substituted 1,2,3-triazole-TSAO analogues. Several 5-substi tuted 1,2,3-triazole-TSAO derivatives proved to be potent inhibitors of HIV -1 replication with higher antiviral selectivity than that of the parent TS AO prototype.