Synthesis and anti-HIV-1 activity of novel 10-thiaisoalloxazines, a structural analog of C-5 and/or C-6 substituted pyrimidine acyclonucleoside.
A series of novel 10-thiaisoalloxazine derivatives bearing an alkoxymethyl or benzyloxymethyl moiety at the N-1 position has been synthesized through the bromination of 1-substituted-5-hydroxyuracils and subsequent condensation with aminobenzenethiol in a one-pot reaction. Contrary to the previous report, the formation of intermediary 5,6-diethoxy-5-hydroxy-5,6-dihydrouracil seems to be not the necessary factor for the formation of the thiaisoalloxazines, since the reaction proceeds in tetrahydrofuran (THF) or acetonitrile far more smoothly than in ethanol. The anti-human immunodeficiency virus (HIV)-1 activity of the resulted thiaisoalloxazine derivatives was evaluated in lymphocyte cells based on the inhibitory activity against the viral-induced cytopathic activity. Among the derivatives, compounds 6, 7, and 8 bearing an alkoxymethyl moiety at the N-1 position exhibited modest inhibitory activity towards the cytotopathic effect of HIV-1.
Miyashita
Takanori
T
Biochemical Division, Yamasa Corporation, Chiba, Japan.
Baba
Masanori
M
Shigeta
Shiro
S
Mori
Kenya
K
Shinozuka
Kazuo
K
D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D005415:Flavins / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D015497:HIV-1 / Q000187:drug effects* / Q000472:pathogenicity / Q000502:physiology; D006801:Humans; D011741:Pyrimidine Nucleosides / Q000737:chemistry*; D013329:Structure-Activity Relationship; D014779:Virus Replication / Q000187:drug effects
D019380:Anti-HIV Agents; D005415:Flavins; D011741:Pyrimidine Nucleosides