Synthesis and antiviral activity of 5- and 5'-substituted thymidine analogs.
The 5'-O-p-tolylsulfonyl derivatives of 5-chloro-, 5-bromo-, and 5-iodo-2'-deoxyuridine were synthesized and converted into the corresponding 5-halo-5'-azido-2',5'-dideoxyuridines (5-7). Reduction of 5-chloro-5'-azido-2',5'-dideoxyuridine (5) afforded 5-chloro-5'-amino-2',5'-dideoxyuridine (10, ACIU); however, similar efforts to prepare 5-bromo-5'-amino-2',5'-dideoxyuridine (11) and 5-iodo-5'-amino-2',5'-dideoxyuridine (12) by reduction of the corresponding 5'-azido precursor resulted in the formation of 5'-amino-2',5'-dideoxyuridine (9). 5-Bromo-5'-amino-2',5'-dideoxyuridine (11, ABrU) and 5-iodo-5'-amino-2',5'-dideoxyuridine (12, AIU) were prepared by halogenation of the 5-mercuriacetate of 5'-amino-2',5'-dideoxyuridine. The 5'-amino-2',5'-dideoxy analogs of 5-methyl-, 5-chloro-, 5-bromo-, and 5-iodo-2'-deoxyuridine possess antiviral activity against herpes simplex virus but exhibit no inhibitory activity against sarcoma 180 (murine) or Vero (monkey) cells in culture.
D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis*; D002460:Cell Line; D002471:Cell Transformation, Neoplastic / Q000187:drug effects; D066298:In Vitro Techniques; D051379:Mice; D012510:Sarcoma 180 / Q000378:metabolism; D018139:Simplexvirus / Q000187:drug effects; D013936:Thymidine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D014779:Virus Replication / Q000187:drug effects
D000998:Antiviral Agents; D013936:Thymidine