Table 3.
Heterobase substitutions and ribose modifications of selected flaviviral RdRp nucleoside inhibitors.
| Heterobase identity/modification | Type of the glycosidic bond | Ribose substitution | Ribose position | Example |
|---|---|---|---|---|
| 4-Aza-7,9-dideazaadenie 4-Aza-7,9-dideazaadenie |
C-glycosidic C-glycosidic |
-CN (α) -CN (α) |
C1′ C1′ |
GS-441524 GS-5734 |
| Adenine 7-Deazaadenine Guanine Cytosine Uracil 6-O-methylguanine |
N-glycosidic N-glycosidic N-glycosidic N-glycosidic N-glycosidic N-glycosidic |
-CH3 (β) -CH3 (β) -CH3 (β) -CH3 (β) -CH3 (β) -CH3 (β) |
C2′ C2′ C2′ C2′ C2′ C2′ |
2′-C-methyladenosine 7-Deaza-2′-C-methyladenosine 2′-C-methylguanosine 2′-C-methylcytidine 2′-C-methyluridine INX-08189 |
| Uracil | N-glycosidic | -F (α), CH3 (β) | C2′ | Sofosbuvir |
| Adenine 7-Deazaadenine 7-Deaza-7-carbamoyladenine |
N-glycosidic N-glycosidic N-glycosidic |
-ethynyl (β) -ethynyl (β) -ethynyl (β) |
C2′ C2′ C2′ |
2′-C-ethynyladenosine NITD008 NITD449 |
| Cytosine Cytosine |
N-glycosidic N-glycosidic |
-H (α), OH (β) + N3 (α) –N3 (α) |
C2′+ C4′ C4′ |
4′-Azido 4′-Azido-aracytidine |
| 9-Deazaadenine | C-glycosidic | O exchanged for N | – | BCX4430 |
| 3-Oxopyrazine-2-carboxamide | N-glycosidic | No substitution | – | T-1106 |
| 6-Methyl-7-deazaadenine | N-glycosidic | No substitution | – | 6-Methyl-7-deazadenosine |
| Uracil Uracil |
N-glycosidic N-glycosidic |
Trityl Trityl |
C2′ and C5′ C3′ and C5′ |
2′,5′di-O-trityluridine 3′,5′di-O-trityluridine |