MONONUCLEOTIDE AND DINUCLEOTIDE ANALOGUES AND INTERMEDIATES THEREFOR

摘要

A compound of formula (I) or a pharmaceutically acceptable salt thereof, where R1 is hydrogen, R1a or a group of formula (II), R?1?a is R?1¿b or a protecting group Q, R1b is C1-C20 alkyl, C2-C20 alkenyl, C3-C10 cycloalkyl, C6-C15 aryl, C7-C16 aralkyl or a 5- or 6- membered heterocyclic group attached by a carbon atom in the heterocyclic group to the indicated phosphorus atom, R2 is hydrogen, R2a or -OR15, provided that when R1 is hydrogen, R2 is R2a or -OR15, R2a is a C1-C20 aliphatic group, a C3-C10 cycloaliphatic group, a C6-C15 aromatic group, a C7-C16 araliphatic group, or a 5- or 6- membered heterocyclic group attached by a carbon atom in the heterocyclic group to the indicated phosphorus atom, R3 is hydrogen, halogen, hydroxy, R?16, -OR16, OSO¿2R?16, OCOR16¿ or tri(C¿1?-C15 hydrocarbyl) silyloxy, R?4 is R4¿a or together with R6 denotes a valence bond, R4a is hydrogen, halogen or R17, R5 is hydrogen, halogen, hydroxy, R?18, -OR18, -OCOR18, OSO¿2R18, or tri(C¿1?-C15 hydrocarbyl) silyloxy, R?6¿ is hydrogen, halogen or R19, or together with R4 denotes a valence bond, R7 is hydrogen, or an atom or group capable of terminating a replicating strand of a nucleic acid or of inhibiting viral DNA synthesis, other than a group connected to the indicated furanose ring through an oxygen atom, or together with R8 denotes a valence bond, R8 is R8a, or together with R7 denotes a valence bond, R8a is hydrogen, halogen, hydroxy, R?20, -OR20, -OCOR20¿, -OSO¿2R?20 or tri(C¿1?-C15 hydrocarbyl) silyloxy, R?9¿ is a monovalent nucleoside base radical, R10 is hydrogen or R10a, R10a is R?21, -COR21, -SO¿2R21 or tri(C¿1?-C15 hydrocarbyl)silyl, R?11¿ is hydrogen, halogen, hydroxy, R?22, -OR22, -OCOR22¿, -OSO¿2R?22 or Z, R12 is hydrogen, halogen or R23. R13 is hydrogen or R13a, R13a is halogen, hydroxy, R?24, -OR24, -OCOR24¿, -OSO¿2R?24 or tri(C¿1?-C15 hydrocarbyl)silyloxy, R?14¿ is a monovalent nucleoside base radical, R15 is hydrogen or R15a, R15a is a C1 to C10 aliphatic group, a C3 to C8 cycloaliphatic group, a C6 to C15 aromatic group or a C7 to C16 araliphatic group, R?16, R17, R18, R19, R20, R21, R22, R23 and R24¿ are independently a C¿1? to C10 aliphatic group, a C3 to C10 cycloaliphatic group, a C6 to C15 aromatic group or a C7 to C30 araliphatic group, and Z is substituted or unsubstituted C6 to C10 aryloxythiocarbonyloxy.