Novel bicyclic sugar modified nucleosides: synthesis, conformational analysis and antiviral evaluation.
Methodology previously described by us was applied to the formation of novel conformationally restrained bicyclic sugar modified nucleosides, with introduction of an oxazole and a thiocarbamate ring at the 2('),3(')-positions of the ribonucleosides. Two novel alkyl derivatives of 2('),3(')-dideoxy-2('),3(')-oxazole-beta-d-uridine and a novel uridine 2('),3(')-thiocarbamate were successfully synthesised. Conformational evaluation of all the synthesised compounds was conducted using the theoretical potential energy calculation via the macromodel v.6.0 molecular modelling programme. The conformationally restrained nucleosides described were evaluated against a wide range of DNA and RNA viruses. None of the compounds showed specific antiviral effects at subtoxic concentrations.
Kifli
Nurolaini
N
Welsh School of Pharmacy, Cardiff University, King Edward VII Avenue, Cardiff CF10 3XF, UK.
Thet Htar
Thet
T
De Clercq
Erik
E
Balzarini
Jan
J
Simons
Claire
C
D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002241:Carbohydrates / Q000737:chemistry*; D045744:Cell Line, Tumor; D003500:Cyclization; D004267:DNA Viruses / Q000187:drug effects; D004353:Drug Evaluation, Preclinical; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008968:Molecular Conformation; D015394:Molecular Structure; D009705:Nucleosides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D012328:RNA Viruses / Q000187:drug effects; D013859:Thiocarbamates / Q000737:chemistry
D000998:Antiviral Agents; D002241:Carbohydrates; D009705:Nucleosides; D013859:Thiocarbamates