Compounds, compositions, and methods for the treatment of disease

A compound of Formula (II):

• or a pharmaceutically acceptable salt or stereoisomer thereof,
• wherein:
• Tm is a targeting moiety;
• each of B1 and B2 is independently a purinyl nucleobase or pyrimidinyl nucleobase;
• each of X1 and X2 is independently O or S;
• each of Y1 and Y2 is independently O, S, or N(R5);
• each of Z1 is independently O or S;
• each of Z2 and Z3 is independently absent, —C1-C20-alkylene, C1-C20 heteroalkylene, —OC(O)OC1-C20-alkylene, -cycloalkylene-, -heterocyclyl-, -aryl-, or -heteroaryl-, wherein each -cycloakyl-, -heterocyclyl-, -aryl- or -heteroaryl- is optionally substituted with one or more R4;
• Z4 is self-immolative group-C1-C20-alkylene-Q1, heterocyclyl-C1-C20-alkylene-Q, —OH, —N(R5)2, SR5, —CHO, —C(O)N(R5)2, —OC(O)N(R5)2, —N(R5)C(O)OR5, aryl, heteroaryl, —S(O)R5, —S(O)2R5, —S(O)N(R5)2, —S(O)2N(R5)2, —N(R5)S(O)R5, —OSi(C1-C4 alkyl)3, or —C(O)C2-C6 alkenyl;
• Z5 is a self-immolative group or absent;
• T is a spacer group or absent;
• L1 is absent, —C1-C6-alkylene or —C1-C6-heteroalkylene;
• L2 is absent, —C1-C6-alkylene or —C1-C6-heteroalkylene, wherein each alkylene and heteroalkyl is optionally substituted with one or more R6;
• L3 is absent, —C1-C20-alkylene, —O—, —N(R5)—, —S—, —S(O)—, —S(O)2—, —S(O)N(R5)—, —S(O)2N(R5)—, —N(R5)S(O)—, —N(R5)S(O)2—, —C(O)—, —C(O)O—, —OC(O)—, —C(O)N(R5)—, —N(R5)C(O)—;
• L4 is —C1-C20-alkylene, —C1-C20-heteroalkylene, —C1-C20-alkenylene, —C1-C20-alkynylene, or an oligopeptide, wherein the oligopeptide is optionally substituted by one or more R16;
• L5 is a linker connecting Z4 and Z5, or is absent;
• Q1 is C(O), C(S), or CH2;
• each of R1 and R2 is independently hydrogen, halo, —CN, —C1-C20 alkyl, or —OR7;
• R3 is hydrogen, —C1-C20-alkyl, —C1-C20 heteroalkyl, —OC(O)OC1-C20 alkyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl,
• wherein each alkyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is optionally substituted with one or more R8;
• each R4 is independently hydrogen, —C1-C20 alkyl, —O—C1-C20 alkyl, —C1-C20 heteroalkyl, halo, —CN, —NO2 or —OH;
• R5 is hydrogen or —C1-C20 alkyl;
• R6 is halo, —CN, —C1-C20 alkyl, —OR7, oxo, cycloalkyl, heterocyclyl, aryl, or heteroaryl, wherein each alkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is optionally substituted with one or more R9;
• R7 is hydrogen, —C1-C20 alkyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl,
• wherein each alkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is optionally substituted with one or more R9;
• each R8 is independently —C1-C20 alkyl, —C1-C20 heteroalkyl, —C(O)—C1-C20 alkyl, —OC(O)—C1-C20 alkyl, —C(O)O—C1-C20 alkyl, —OC(O)O—C1-C20 alkyl, —C(O)N(R5)—C1-C20 alkyl, —N(R5)C(O)—C1-C20 alkyl, —OC(O)N(R5)—C1-C20 alkyl, —O-aryl, —O-heteroaryl, —C(O)-aryl, —C(O)-heteroaryl, —OC(O)-aryl, —C(O)O-aryl, —OC(O)-heteroaryl, —C(O)O-heteroaryl, —C(O)O-aryl,
• —C(O)O-heteroaryl, —C(O)N(R5)-aryl, —C(O)N(R5)-heteroaryl, —N(R5)C(O)-aryl, —N(R5)2C(O)-aryl, or —N(R5)C(O)-heteroaryl, —S(O)2N(R)-aryl, wherein each alkyl, heteroalkyl, aryl, and heteroaryl is optionally substituted by one or more R9;
• each R9 is independently —C1-C20 alkyl, —O—C1-C20 alkyl, —C1-C20 heteroalkyl, halo, —CN, —OH, oxo, aryl, heteroaryl, —O-aryl, or —O-heteroaryl;
• and
• each R16 is independently, —C1-C20 alkyl, —C1-C20 heteroalkyl, —OC(O)OC1-C20 alkyl, C(O)N(R4)2 cycloalkyl, heterocyclyl, aryl, or heteroaryl.