Nucleotide mimics and their prodrugs

A compound of Formula (XVI):

• wherein X0 and X5 are selected independently from the group consisting of O, S;
• X6 is selected from the group consisting of NH and CY2,
• wherein Y is selected from the group consisting of H, F, Cl, Br, and alkyl;
• wherein X2, X3, and X4 are selected independently from the group consisting of O and S;
• wherein X8, X9, and X10 are selected independently from the group consisting of OH, SH, NH2, R, R*, OR, SR, NHR, and NR2;
• X7 is −BH3M+;
• wherein ni s 1;
• wherein at least one of X8, X9 and X10 is R*;
• wherein Nu is selected from the group consisting of natural nucleosides, sugar-modified nucleosides, base-modified nucleosides, and nucleosides with both sugar and base modifications;
• wherein Nu is linked to X0 through CH2 of the sugar moiety of Nu;
• and
• R is selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, acyl, and aralkyl each optionally containing one or more hetero atoms;
• with the proviso that one of X8-X10 is selected from R*, wherein R* is a prodrug substituent selected from the group consisting of:
• acylthioethoxy, (SATE) RCOSCH2CH2O—, RCOSCH2CH2O—W—O—, RCOSCH2CH2O—W—S—, RCOSCH2CH2O—W—NH—, RCOSCH2CH2O—W—, RCOSCH2CH2O—W—CY2—, acyloxymethoxy, RCOOCH2O—, RCOOCH2O—W—O—, RCOOCH2O—W—S—, RCOOCH2O—W—NH—, RCOOCH2O—W—, RCOOCH2O—W—CY2—, alkoxycarbonyloxymethoxy, ROCOOCH2O—, ROCOOCH2O—W—O—, ROCOOCH2O—W—S—, ROCOOCH2O—W—NH—, ROCOOCH2O—W—, ROCOOCH2O—W—CY2—, acylthioethyldithioethoxy (DTE) RCOSCH2CH2SSCH2CH2O—, RCOSCH2CH2SSCH2CH2O—W—, RCOSCH2CH2SSCH2CH2O—W—O—, RCOSCH2CH2SSCH2CH2O—W—S—, RCOSCH2CH2SSCH2CH2O—W—NH—, RCOSCH2CH2SSCH2CH2O—CY2—, acyloxymethyiphenylmethoxy, (PAOB) RCO2—C6H4—CH2—O—RCO2—C6H4—CH2—O—W—, RCO2—C6H4-CH2—O—W—O—, RCO2—C6H46—CH2—O—W—S—, RCO2—C6H4—CH2—O—W—NH—, RCO2—C6H4—CH2—O—W—CY2—, 1,2-O-diacyl-glyceryloxy, RCOO—CH2—CH(OCOR)—CH2O—, 1,2-O-dialkyl-glyceryloxy, RO—CH2—CH(OR)—CH2O—, 1,2-S-dialkyl-glyceryloxy, RS—CH2—CH(SR)—CH2O—, 1-O-alkyl-2-O-acyl-glyceryloxy, RO—CH2—CH(OCOR)—CH2O—, 1-S-alkyl-2-O-acyl-glyceryloxy, RS—CH2—CH(OCOR)—CH2O—, 1-O-acyl-2-O-alky-glyceryloxy, RCOO-CH2—CH(OR)—CH2O—, 1-O-acyl-2-S-alkyl-glyceryloxy, RCOO—CH2—CH(SR)—CH2O—,
• where W is alkyl.

A compound of Formula (I) which may be a D- or L-nucleotide:

• wherein
• A is O;
• R4′ is —L-R5
• L is CY2O, wherein Y is selected from the group consisting of H, F, Cl, Br, and alkyl;
• R5 is a tri-phosphate moiety of Formula (II):
• wherein n is 0 or 1;
• X2, X3, and X4 selected independently from the group consisting of O, S;
• X5 is O or S;
• X6 is NH or CY2;
• X7 is −BH3M+
• X8, X9, and X10 are selected independently from the group consisting of OH, SH, NH2, R, OR, SR, NHR, and NR2;
• R2′ and R3′ are selected independently from the group consisting of H, F, Cl, Br, OH, SH, NH2, NHOH, N3, NO2, CHO, COOH, CN, CONH2, COOR, R, OR, SR, SSR, NHR, and NR2;
• alternatively, R2 and R2 together and R3 and R3 together independently are ═J-Q, where J is N, CH, CF, CCl, or CBr and Q is H, F, Cl, Br, N3, or R;
• R1, R2, R3, and R4 are each H;
• D is a nucleoside base of Formula (III):
• Z1 is N, CH or C-G3;
• G1, G2, and G3 are selected independently from the group consisting of H, F, Cl, Br, I, OH, SH, NH2, R, OR, SR, NHR, and NR2;
• and
• R is selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, acyl, and aralkyl each optionally containing one or more hetero atoms;
• with the proviso that:
• when L is CH2O and linked to P through CH2 and if A is O or CH2 and X10 alkyl, aryl, alkoxy, aryloxy, alkylamino, arylamino, or glyceroloxy, X6 is not methylene and substituted methylene.

A compound of Formula (XVII):

• wherein X0 is O or S
• and X6 is NH or CY2,
• where Y is H, F, Cl, Br or alkyl;
• wherein X2 is O or S;
• wherein X7 −BH3M+;
• and
• wherein X9 and X10 are selected independently from the group consisting of OH, SH, NH2, NHOH, −BH3M+, R, OR, SR and NHR;
• wherein Nu is linked to X0 through CH2 of the sugar moiety of Nu;
• and
• R is selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, acyl, and aralkyl each optionally containing one or more hetero atoms;
• wherein Nu is selected from the group consisting of
• cytidine,
• uridine,
• 2′-deoxycytidine,
• thymidine,
• 3′-azido-3′-deoxythymidine,
• 3′-azido-2′,3′-dideoxyuridine,
• 3′-azido-2′,3′-dideoxycytidine,
• 3′-deoxythymidine,
• 2′,3′-dideoxyuridine,
• 2′,3′-dideoxycytidine,
• 6-azauridine,
• 6-azathymidine,
• 6-azacytidine,
• 5-azacytidine,
• 5-fluorocytidine,
• 5-iodocytidine,
• 5-bromocytidine,
• 5-chlorocytidine,
• 5-fluorouridine,
• 5-iodouridine,
• 5-bromouridine,
• 5-chlorouridine,
• 2′-C-methylcytidine,
• 2′-C-methyluridine,
• 2′-C-methylthymidine,
• 2′-deoxy-2′-fluorocytidine,
• 2′-deoxy-2′-fluorouridine,
• 2′-α-fluorothymidine,
• 2′-C-ethynylcytidine,
• 2′-C-ethynyluridine,
• 2′-C-ethynyl-5-methyluridine,
• 3′-C-ethynylcytidine,
• 3′-C-ethynyluridine,
• 3′-C-ethynyl-5-methyluridine,
• 3′-deoxycytidine,
• 3′-deoxyuridine,
• 4′-C-ethynylcytidine,
• 4′-C-ethynyluridine,
• 4′-C-ethynylthymidine,
• 2′-deoxy-6-azauridine,
• 2′-deoxy-5-fluorouridine,
• 2′-deoxy-5-fluorocytidine,
• 2′-deoxy-5-iodouridine,
• 2′-deoxy-5-iodocytidine,
• 3′-deoxy-6-azauridine,
• 3′-deoxy-5-fluorouridine,
• 3′-deoxy-5-iodouridine,
• 3′-deoxy-5-fluorocytidine,
• 2′,3′-dideoxy-6-azauridine,
• 2′,3′-dideoxy-5-fluorouridine,
• 2′,3′-dideoxy-5-fluorouridine, and
• 2′,3′-dideoxy-5-iodocytidine.