Author:

Keywords:

Anti-HIV Agents, Cell Line, Drug Evaluation, Preclinical, HIV-1, HIV-1 Reverse Transcriptase, Lymphocytes, Models, Chemical, Molecular Structure, Protein Binding, Reverse Transcriptase Inhibitors, Spiro Compounds, Structure-Activity Relationship, Thymidine, Virus Replication, Science & Technology, Life Sciences & Biomedicine, Biochemistry & Molecular Biology, Pharmacology & Pharmacy, Virology, AIDS, non-nucleoside HIV-1 RT inhibitors, TSAO-1,2,3-triazoles, 3 '-spironucleosides, HIV-1 REVERSE-TRANSCRIPTASE, HIV-1-SPECIFIC RT-INHIBITORS, HIGHLY SELECTIVE INHIBITORS, ANTI-HIV-1 ACTIVITY, NUCLEOSIDE ANALOGS, TSAO DERIVATIVES, NONNUCLEOSIDE INHIBITORS, PYRIMIDINE NUCLEOSIDES, RESISTANCE MUTATIONS, AUTOMATED DOCKING, HIV Reverse Transcriptase, Uridine, 0304 Medicinal and Biomolecular Chemistry, 0601 Biochemistry and Cell Biology, 1117 Public Health and Health Services, 3404 Medicinal and biomolecular chemistry

Abstract:

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