Synthesis and hypnotic and anti-human immunodeficiency virus-1 activities of N3-substituted 2'-deoxy-2'-fluorouridines.
Reaction of 9-[3,5-di-O-(tetrahydropyran-2-yl)-beta-D-arabinofuranosyl]uracil (2) with diethylaminosulfur trifluoride in the presence of pyridine afforded 2'-deoxy-2'-fluororiboside 3a, from which 2'-deoxy-2'-fluorocytidine (4b) has been synthesized in good yield. Compound 3a was deprotected and subsequently treated with various benzyl halides or 2-chloro-4-fluoroacetophenone to give corresponding N3-substituted 2'-deoxy-2'-fluorouridines 5a-c and 6. Compounds 5a-c, as well as 6, showed weak hypnotic activity in mice. Compound 4b showed moderate antiviral activity against human immunodeficiency virus-1 but 3b, 5a-c, and 6 were virtually inactive.
Sato
Y
Y
Department of Pharmaceutical Sciences, Tokushima Bunri University, Japan.
Utsumi
K
K
Maruyama
T
T
Kimura
T
T
Yamamoto
I
I
Richman
D D
DD
D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D003857:Deoxyuridine / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D006993:Hypnotics and Sedatives / Q000138:chemical synthesis* / Q000494:pharmacology; D051379:Mice
D000998:Antiviral Agents; D006993:Hypnotics and Sedatives; D003857:Deoxyuridine