Prodrug for delivering sirna into cell

An oligonucleotide, comprising one, two or more compounds of formula (Ia), or a pharmaceutically acceptable salt, tautomer or stereoisomer thereof:

• wherein,
• is selected from ORa or NRbRc, or represents a bond connecting to a hydroxyl or a sulfydryl of the 5′ carbon of the ribose of an adjacent nucleotide;
• X1 is a bond connecting to a hydroxyl or a sulfydryl of the 2′ or 3′ carbon of the ribose of the other adjacent nucleotide;
• Ra is selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl or C2-6 alkynyl, which is optionally deuterated or fully deuterated;
• Rb and Rc is independently selected from H, C1-6 alkyl or C1-6 haloalkyl;
• Rb and Rc may optionally be substituted with D, C6-10 aryl or 5-10-membered heteroaryl, or fully deuterated;
• X3 is independently selected from O or S;
• T is
• each RT1 is independently selected from H, D, halogen, CN, C1-6 alkyl, C1-6 haloalkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl or GalNAc-containing chain, which is optionally deuterated or fully deuterated;
• each RT2 is independently selected from H, D, halogen, CN, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl or C2-6 alkynyl, which is optionally deuterated or fully deuterated;
• m is 0, 1, 2, 3, 4 or 5;
• X is selected from bond, —O—, —S—, —C(O)—, —C(O)O—, —OC(O)—, —OC(O)NRX1—, —NRX1C(O)O—, —NRX1C(O)— or —C(O)NRX1—;
• RX1 is selected from H, halogen, C1-6 alkyl or C1-6 haloalkyl, which is optionally deuterated or fully deuterated;
• L is —Ar—(CH2)1-6—O—, wherein each CH2 may optionally be substituted with R #;
• R # is selected from H, D, halogen, CN, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl or C2-6 alkynyl, which is optionally deuterated or fully deuterated;
• Ar in L is linked to X;
• the oxygen atom in L is linked to the phosphorus atom;
• Ar is selected from C3-10 cycloalkyl, 3-10-membered heterocyclyl, C6-10 aryl or 5-14-membered heteroaryl;
• C3-10 cycloalkyl, 3-10-membered heterocyclyl, C6-10 aryl or 5-10-membered heteroaryl may optionally be substituted with 1, 2, 3, 4 or 5 R*;
• R* is selected from H, D, halogen, CN, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl or C2-6 alkynyl, which is optionally deuterated or fully deuterated.

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

• wherein,
• each RT1 is independently selected from H, D, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl or GalNAc-containing chain, which is optionally deuterated or fully deuterated;
• each RT2 is independently selected from H, D, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl or C2-6 alkynyl, which is optionally deuterated or fully deuterated;
• m is 0, 1, 2, 3, 4 or 5;
• X is selected from bond, —O—, —S—, —C(O)—, —C(O)O—, —OC(O)—, —OC(O)NRX1—, —NRX1C(O)O—, —NRX1C(O)— or —C(O)NRX1—;
• RX1 is selected from H, C1-6 alkyl or C1-6 haloalkyl, which is optionally deuterated or fully deuterated;
• L is —Ar—(CH2)—O—, wherein CH2 may optionally be substituted with 1 or 2 R #;
• R # is selected from H, D, C1-6 alkyl or C1-6 haloalkyl, which is optionally deuterated or fully deuterated;
• Ar is selected from C6-10 aryl or 5-10-membered heteroaryl;
• C6-10 aryl or 5-10-membered heteroaryl may optionally be substituted with 1, 2 or 3 R*;
• R* is selected from C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl or C2-6 alkynyl, which is optionally deuterated or fully deuterated;
• PG is selected from a protecting group.