title: 1,2,3-Triazole-[2',5'-bis-O-(tert-butyldimethylsilyl)-beta-D- ribofuranosyl]-3'-spiro-5"-(4"-amino-1",2"-oxathiole 2",2"-dioxide) (TSAO) analogues: synthesis and anti-HIV-1 activity.
abstract: 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.
authors.affiliation: Instituto de Química Médica (C.S.I.C.), Madrid, Spain.
authors.forename: R
authors.initials: R
authors.lastname: Alvarez
authors.forename: S
authors.initials: S
authors.lastname: Velázquez
authors.forename: A
authors.initials: A
authors.lastname: San-Félix
authors.forename: S
authors.initials: S
authors.lastname: Aquaro
authors.forename: E
authors.initials: E
authors.lastname: De Clercq
authors.forename: C F
authors.initials: CF
authors.lastname: Perno
authors.forename: A
authors.initials: A
authors.lastname: Karlsson
authors.forename: J
authors.initials: J
authors.lastname: Balzarini
authors.forename: M J
authors.initials: MJ
authors.lastname: Camarasa
mesh_terms: D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001483:Base Sequence; D002478:Cells, Cultured; D054303:HIV Reverse Transcriptase; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D008969:Molecular Sequence Data; D018894:Reverse Transcriptase Inhibitors; D013141:Spiro Compounds / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013936:Thymidine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D014230:Triazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D014529:Uridine / Q000031:analogs & derivatives
chemical_list: D000998:Antiviral Agents; D018894:Reverse Transcriptase Inhibitors; D013141:Spiro Compounds; D014230:Triazoles; D054303:HIV Reverse Transcriptase; D013936:Thymidine; C075132:TSAO-T; D014529:Uridine