[Synthesis and study of 5-(trialkylsilyl)pyrimidine nucleosides. A new alpha-2'-deoxynucleoside with antiherpes activity].
Glycosylation of 5-trimethylsilyl- and 5-triethylsilyluracil as well as 5-trimethylsilylcytosine with 2-deoxy-3,5-di-O-p-toluyl-alpha-D-ribofuranosylchloride and subsequent deacylation led to alpha- and beta-anomers of 5-Me3SidUrd, 5-Et3SidUrd and 5-Me3SidCyd. 1-(alpha-D-Arabinofuranosyl)-5-trimethylsilyluracil was synthesized starting from the derivatives of 2,3,5-tri-O-benzoyl-D-arabinofuranose and then converted to alpha-5-Me3SidUrd via 1-(2,2'-anhydro-alpha-D-ribofuranosyl)-5-trimethylsilyluracil and 1-(2-chloro-2-deoxy-alpha-D-arabinofuranosyl)-5-trimethylsilyluracil+ ++. Out of all synthesized compounds, only alpha-5-Me3SidUrd inhibits the replication of HSV-1 both in vitro and in vivo; it also exerts a pronounced therapeutic effect in guinea pigs with herpes genitalis induced by HSV-2. The resistance of alpha-5-Me3SidUrd to pyrimidine phosphorylases facilitates its antiviral activity in vivo.
D000818:Animals; D055598:Chemical Phenomena; D002621:Chemistry; D004660:Encephalitis / Q000188:drug therapy* / Q000209:etiology; D005260:Female; D006168:Guinea Pigs; D006558:Herpes Genitalis / Q000188:drug therapy*; D006561:Herpes Simplex / Q000188:drug therapy*; D008297:Male; D011741:Pyrimidine Nucleosides / Q000138:chemical synthesis* / Q000627:therapeutic use; D051381:Rats; D012825:Silicon / Q000138:chemical synthesis*; D014297:Trimethylsilyl Compounds / Q000138:chemical synthesis* / Q000627:therapeutic use
D011741:Pyrimidine Nucleosides; D014297:Trimethylsilyl Compounds; D012825:Silicon
Sintez i izuchenie 5-(trialkilsilil)pirimidinovykh nukleozidov. Novyĭ alpha-2'-dezoksinukleozid s antigerpeticheskoĭ aktivnost'iu.