Synthesis and antiviral activity of the carbocyclic analogues of 5-ethyl-2'-deoxyuridine and of 5-ethynyl-2'-deoxyuridine.
The carbocyclic analogue of the antiviral agent 5-ethyl-2'-deoxyuridine (EDU) was synthesized by two routes. The pivotal step in the first route is the reaction of lithium dimethylcuprate with the carbocyclic analogue of 5-(bromomethyl)-2'-deoxyuridine dibenzoate (6). The second route is based on the synthesis of the carbocyclic analogue of 5-ethynyl-2'-deoxyuridine (12) by a coupling reaction catalyzed by bis(triphenylphosphine)palladium(II) chloride and copper(I) iodide, a method reported recently (Robins and Barr) for the synthesis of the true nucleoside 5-ethynyl-2'-deoxyuridine (1b). The carbocyclic analogue of EDU inhibits the replication of type 1 and type 2 herpes simplex viruses in Vero cells. The carbocyclic analogue of 5-ethynyl-2'-deoxyuridine has modest activity against herpes simplex virus, types 1 and 2.
D000998:Antiviral Agents; D055598:Chemical Phenomena; D002621:Chemistry; D003857:Deoxyuridine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology / Q000627:therapeutic use; D018139:Simplexvirus / Q000187:drug effects*; D014740:Vidarabine / Q000494:pharmacology
D000998:Antiviral Agents; C022811:edoxudin; C047640:5-ethyl-1-(3-hydroxy-4-(hydroxymethyl)cyclopentyl)-2,4(1H,3H)-pyrimidinedione; C047641:5-ethynyl-1-(3-hydroxy-4-(hydroxymethyl)cyclopentyl)-2,4(1H,3H)-pyrimidinedione; D014740:Vidarabine; D003857:Deoxyuridine