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Synthesis and antiviral activity of 5- and 5'-substituted thymidine analogs

Journal Article · · J. Med. Chem.; (United States)
DOI:https://doi.org/10.1021/jm00226a009· OSTI ID:6855467
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, AClU); 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. 2 tables.
Research Organization:
Yale Univ., New Haven
OSTI ID:
6855467
Journal Information:
J. Med. Chem.; (United States), Journal Name: J. Med. Chem.; (United States) Vol. 19:4; ISSN JMCMA
Country of Publication:
United States
Language:
English