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A series of novel acyclic nucleosides. II . Synthesis of acyclic nucleosides bearing an imidazo[4,5‐ d ] [1,3]oxazine ring
Author(s) -
Matsumoto Hiroatsu,
Kaneko Chisato,
Mori Takeo,
Mizuno Yoshihisa
Publication year - 1990
Publication title -
journal of heterocyclic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.321
H-Index - 59
eISSN - 1943-5193
pISSN - 0022-152X
DOI - 10.1002/jhet.5570270525
Subject(s) - chemistry , methyl iodide , acetic anhydride , imidazole , stereochemistry , ring (chemistry) , isothiocyanate , medicinal chemistry , organic chemistry , catalysis
Novel acyclic nucleosides 3a,b,c where N‐1 of acyclovir is replaced by oxygen atom were prepared. Thus, 1‐[(2‐acetoxyethoxy)methyl]‐5‐amino‐4‐ethoxycarbonylimidazole ( 9 ) was treated with ethoxycarbonyl isothiocyanate or benzoyl isothiocyanate to give 11e,f . Methylation of the latter with methyl iodide afforded S ‐methylisothiourea derivative 12f which was treated with alkali and subsequently the mixture was neutralized to give 5‐amino‐3‐[(2‐hydroxyethoxy)methyl]‐3 H ‐imidazo[4,5‐ d ][1,3]oxazin‐7‐one ( 3a ). Compounds 3b,c were obtained by treatment of acetic anhydride or propionic anhydride with sodium 5‐amino‐1‐[(2‐hydroxyethoxy)methyl]imidazole‐4‐carboxylate ( 7 ) which was prepared via 5‐amino‐[(2‐acetoxyethoxy)methyl]‐imidazole‐4‐carboxamide ( 5 ). Evaluation of acyclic oxanosine analogs for cytotoxicity and activity against herpes simplex virus type 1 (HSV‐1) revealed that all the derivatives tested were inactive, but cytotoxicity were similar or less as compared to that of acyclovir.