Nucleotide substitute having enhanced stability

A compound of formula (X), or a pharmaceutically acceptable salt, tautomer or stereoisomer thereof:

• wherein,
• X1 is a bond, O or S;
• X2 is a bond or NR1;
• Y is a bond or [C(Ra)(Rb)]1-4;
• R1 is selected from C1-20 alkyl, C1-20 haloalkyl, C2-20 alkenyl, C2-20 alkynyl, C3-8 cycloalkyl, 3- to 10-membered heterocyclyl, C6-10 aryl, 5- to 14-membered heteroaryl or —[C(O)]p—C1-20 alkylene-(OCH2CH2)nRx, which may be optionally substituted with one or more group selected from halogen, CN, OR′, SR′, NR″R′″, C(O)OR′, C(S)OR′, C(O) NR″R′″, C(S) NR″R′″, OC(O)R′, OC(S)R′, NR″C(O)R′″, NR″C(S)R′″, C1-6 alkyl, C1-6 haloalkyl, C3-8 cycloalkyl, 3- to 10-membered heterocyclyl, C6-10 aryl or 5- to 14-membered heteroaryl;
• wherein R1 may be further optionally deuterated or fully deuterated;
• R2 is selected from H, D or OL2;
• R is selected from H, D, -L-OR′, -L-NR″R′″, Rb or —C(OL2)(Rc)(Rd), wherein R may be optionally deuterated or fully deuterated;
• L1 and L2 are selected from H, a reactive phosphorus group or a protecting group;
• Ra, Rb, Rc and Rd are independently selected from H, D, halogen, CN, -L-OR′, -L-NR″R′″, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, -L-C3-8 cycloalkyl or -L-4-membered to -L-7-membered heterocyclyl;
• wherein Ra, Rb, Rc and Rd are optionally deuterated or fully deuterated;
• wherein L is a bond or C1-6 alkylene, wherein L may be optionally deuterated or fully deuterated;
• R′, R″ and R′″ are independently selected from H, —C1-6 alkylene-OH, —C1-6 alkylene-NH2, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, —C0-6 alkylene-C3-8 cycloalkyl, —C0-6 alkylene-(3- to 10-membered heterocyclyl), —C0-6 alkylene-C6-10 aryl or —C0-6 alkylene-(5- to 14-membered heteroaryl), which is optionally substituted with one or more groups selected from halogen, CN, NO2, OH, NH2, C1-6 alkyl or C1-6 haloalkyl;
• otherwise R″ and R′″ together with the N atom connecting thereto form a 3- to 10-membered heterocyclyl;
• Rx is selected from H, D, OH, OC1-6 alkyl, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-8 cycloalkyl, 3- to 10-membered heterocyclyl, C6-10 aryl or 5- to 14-membered heteroaryl;
• wherein Rx is optionally deuterated or fully deuterated;
• n=0, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10;
• p=0 or 1;
• Rs is selected from H, D, C1-6 alkyl or C1-6 haloalkyl, wherein Rs may also be optionally deuterated or fully deuterated;
• m=0, 1, 2, 3 or 4;
• provided that an OL2 group is present in either R or R2.