Patent ID: 8242087

Claim:
A phosphate-modified nucleoside represented by the structural formula (I) wherein B is a pyrimidine or purine base, or an analogue thereof, optionally substituted with one or two substituents independently selected from the group consisting of halogen, hydroxyl, sulfhydryl, methyl, ethyl, amino and methylamino; R 1 is H or OH; R 3 is hydrogen; W is O or S; and R 2 is a group represented by the structural formula IV: wherein n is 0 Z is selected from the group consisting of O, S, NH and NCH 3 ; each of R 4 and R 5 is independently selected from the group consisting of (CH 2 ) m —COOR 6 and (CH 2 ) m -imidazolyl; R 6 is H or C 1-6 alkyl; m is 0 or 1; and dotted lines represent the point of attachment of Z to the phosphorous atom of formula (I); or the structural formula (I′): wherein B is a pyrimidine or purine base, or an analogue thereof, optionally substituted with one or two substituents independently selected from the group consisting of halogen, hydroxyl, sulfhydryl, methyl, ethyl, isopropyl, amino, methylamino, ethylamino, trifluoromethyl and cyano; R 1 is hydrogen or hydroxyl; R 3 is selected from the group consisting of hydrogen, C 1-6 alkyl, C 3-6 cycloalkyl, aryl-C 1-6 alkyl and 2-cyanoethyl, wherein said C 1-6 alkyl, C 3-6 cycloalkyl or aryl-C 1-6 alkyl is optionally substituted with one or more, preferably 1, 2 or 3, substituents independently selected from the group consisting of halogen, hydroxyl, C 1-6 alkoxy, trifluoromethyl, trifluoromethoxy, nitro, cyano and amino; W is O; and R 2 is a group represented by the structural formula (VI) wherein dotted lines represent the point of attachment of Z to the phosphorous atom of formula (I′); n is 0, 1 or 2; Z is selected from the group consisting of O, S, NH and NCH 3 ; and Ar is an aryl group; and stereoisomers, enantiomers and pharmaceutically acceptable salts thereof, provided that said phosphate-modified nucleoside is not: N-5′-adenylylphosphoramidate L-aspartic acid 1,4-dimethyl ester, N-5′-uridylylphosphoramidate L-aspartic acid 1,4-dimethyl ester, N-5′-thimidylylphosphoramidate L-aspartic acid 1,4-dimethyl ester, N-5′-adenylylphosphoramidate L-aspartic acid 1,4-dimethyl ester, monoammonium salt, N-5′-guanylylphosphoramidate L-aspartic acid 1,4-dimethyl ester, monoammonium salt, N-5′-uridylylphosphoramidate L-aspartic acid 1,4-dimethyl ester, monoammonium salt, N-5′-thymidylylphosphoramidate L-aspartic acid 1,4-dimethyl ester, monoammonium salt, N-5′-citidylylphosphoramidate L-aspartic acid disodium salt, N-5′-uridylylphosphoramidate L-histidine, N-5′-uridylylphosphoramidate L-histidine 1-methyl ester, N-5′-adenylylphosphoramidate L-histidine 1-methyl ester, N-5′-cytidylylphosphoramidate L-histidine 1-methyl ester, or N-5′-uridylylphosphoramidate L-aspartic acid.