Synthesis of 3′,5′‐Cyclic Phosphate and Thiophosphate Esters of 2′‐C‐Methyl Ribonucleosides |
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Authors: | Anna Leisvuori Zafar Ahmed Mikko Ora Leonid Beigelman Lawrence Blatt Harri Lönnberg |
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Institution: | 1. University of Turku, Department of Chemistry, FI‐20014 Turku, (phone: +358‐2‐3336706;2. fax: +358‐2‐3336700);3. AliosBiopharma, 260?E. Grand Ave, 2nd Floor, South San Francisco, CA 94080, USA |
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Abstract: | 2′‐C‐Methylnucleosides are known to exhibit antiviral activity against Hepatitis C virus. Since the inhibitory activity depends on their intracellular conversion to 5′‐triphosphates, dosing as appropriately protected 5′‐phosphates or 5′‐phosphorothioates appears attractive. For this purpose, four potential pro‐drugs of 2′‐C‐methylguanosine, i.e., 3′,5′‐cyclic phosphorothioate of 2′‐C‐methylguanosine and 2′‐C,O6‐dimethylguanosine, 1 and 2 , respectively, the S‐(pivaloyloxy)methyl] ester of 2′‐C,O6‐dimethylguanosine 3′,5′‐cyclic phosphorothioate and the O‐methyl ester of 2′‐C,O6‐dimethylguanosine 3′,5′‐cyclic phosphate, 3 and 4 , respectively, have been prepared. |
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Keywords: | Nucleosides Prodrugs Phosphorothioate |
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