Nucleoside 5'-monophosphate mimics and their prodrugs

A compound of Formula (I):

• 35
• which may be a D- or L-nucleotide;
• wherein:
• A is O, S, CH2, CHF, CF2, or NH;
• R4′ is -L-R5 where L is selected from the group consisting of O, S, NH, NR, CH2, CH2O, CH2S, CH2NH, CH2NR, CHY, CY2, CH2CH2, CH2CHY, and CH2CY2, where Y is F, Cl, Br, or selected from alkyl, alkenyl, and alkynyl optionally containing one or more heteroatoms;
• R5 is a moiety of Formula (II) or (III):
• 36
• where X1, X4, and X6 independently are O, S, NH, or NR;
• X2, X3, and X5 are selected independently from the group consisting of H, F, OH, SH, NH2, NHOH, N3, CN, −BH3M+, R, OR, SR, NHR, NR2, and R*, wherein R* is a prodrug substituent;
• R1, R2, R2′, R3, R3′, and R4 are selected independently from a group consisting of H, F, Cl, Br, I, 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 ═O, ═S, or =J-Q, where J is N, CH, CF, CCl, or CBr, and Q is H, F, Cl, Br, N3 or R;
• Z1, Z2, and Z3 are independently N, CH or C-G2;
• G1 and G2 are selected independently from a group consisting of H, F, Cl, Br, I, OH, SH, NH2, NHOH, NHNH2, N3, NO, NO2, CHO, COOH, CN, CONH2, CONHR, C(S)NH2, C(S)NHR, COOR, R, OR, SR, NHR, and NR2;
• when two or more G 2 groups are present on a molecule, they can be same as or different from one another;
• and
• R is selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, acyl, and aralkyl optionally containing one or more heteroatoms;
• with provisos that:
• (1) at least one of X1, X2, and X3 is not 0, OH or OR, when L is CH2O which is linked to P through O;
• (2) at least one of X1, X2, and X3 is not 0, OH, OC5H6 or OCH2C5H6 when L is CH2CH2, G1 is CONH2, Z1 and Z3 are N, Z2 is CH, R1, R2, R3, R4 are H, and R2′ and R3′ are OH;
• (3) one of X2 and X3 is not NH2 when the other of X2 and X3 is OH, X1 is O, L is CH2O which is linked to P through O, G1 is CONH2, Z1 and Z3 are N, Z2 is CH, R1, R2, R3, and R4 are H, and R2 and R3 are OH;
• (4) X5 is not NH2 when X4 and X6 are O, L is CH2O which is linked to S through O, G1 is CONH2, CSNH2 or CN, Z1 and Z3 are N, Z2 is CH, R1, R2, R3, and R4 are H, and R2′ and R3′ are OH.
• (5) when L is CH2O linked to P through CH2 and R4 is alkyl, alkoxy, halomethyl, CH2—O-t-butyldimethylsilyl, CH2OH, CH2N3, CH2CN, CH2CH2N3, or CH2CH2OH, G1 is not CONHR;
• and
• (6) when L is CH2CH2, CH2O, CH2S, CH2CHF, or CH2CF2 which is linked to P through CH2 and R1, R2, R3, and R4 are all hydrogen, G1 is not CONHR.