Due to the antiviral activity of certain 5-substituted imidazolenucleosidesrelatedtoribavirin, 5-methyl-imidazole-4-carboxamidenucleosideshaving/3-D-ribofuranosyl,2-deoxy-/3-and- -D-ribofuranosyl, and (2-hydroxyethoxy) methylmoieties have been prepared and testedasantiviralagents.l-/J-D-Ribofuranosyl-5-methylimidazole-4-carboxamide(12) was obtained by deacetylation of the correspondingtri-O-acetylnucleoside 11 orbydeacetylationandammonolysis of the block edethyl5-methylimidazole-4-carboxylatenucleoside10, which was prepared from the stannicchloride catalyzed condensation of the trimethylsilylderivativeofethyl4 (5)-methylimidazole-5(4)-carboxylate(8). Glycosylationof4(5)-methylimidazole-5(4)-carboxamide(13)with3,5-di-O-p-toluoyl-2-deoxy-D-eryt/iro-pentofuranosylchlorideviamercuriccyanidemethod provided ananomericmixtureoftheblocked5-methylimidazole-4-carboxamidedeoxynucleoside14alongwithananomericmixtureofthe4-methyl5-carboxamideisomer15. Separationofcompound14intothecorrespondingßandaanomerswasachievedbyconversiontothe3',5'-di-0-acetylderivatives 17 and 18, which after chromatographic separation were deacetylatedtogivel-(2-deoxy-d-D-eryiforo-pentofuranosyl)-5-methylimidazole-4-carboxamide(19)anditsaanomer20. 1-[(2-Hydroxyethoxy)methyl]-5-methylimidazole-4-carboxamide(23)waspreparedbyalkylationoftheimidazole13with(2-acetoxyethoxy) methylbromidefollowedbytreatmentwithmethanohcammonia. All the seimidazolenucleosidesweretestedinHeLacellculturesagainsttype1herpessimplexandvesicularstomatitisviruses. Theribofuranosylderivative12showedasignificantactivityagainsttype1herpessimplexvirus

We thank the C.S.I.C. for three fellowships (R.A.,J.I.A.,and B.A.) and the CAICYT and Antibióticos S.A. for financial support.

Peer reviewed