Codrug that disintegrates in intestine, preparation therefor, and use thereof

A codrug compound shown in the formula I, wherein the codrug compound is formed by coupling the first drug molecule, the second drug molecule and a linker precursor:

• D1-linker-D2;
• I
• wherein,
• D1 is the first drug group;
• and the first drug group is a structural fragment in the first drug molecule which can be connected to the linker;
• D2 is the second drug group;
• and the second drug group is a structural fragment in the second drug molecule which can be connected to the linker;
• and the linker has a structure selected from the group (a), (b) or (c), in each formula, J1 connects to the first drug group, and J2 connects to the second drug group;
• the Glu has a structure selected from the group consisting of:
• wherein the A ring is selected from the group consisting of C6-C10 aryl, 5-10 membered heteroaryl, and 3-12 membered heterocyclic group;
• wherein, R4 is selected from the group consisting of H, C1-6 alkyl, and C1-6 alkyoxy-C1-4 alkylene-C3-12 cycloalkyl, C3-12 cycloalkyl-C1-4 alkylene-;
• wherein, the B-ring and C-ring are independently selected from the group consisting of C6-C10 aryl, 5-10 membered heteroaryl, 3-12 membered heterocyclic group;
• in the above formula (a), (b) and (c), the J1 and J2 are each independently as —(Y)z—, and each Y is selected from the group consisting of —NH—, —C(O)—, —CH═CH—, —NH(CH2)—, —NHC(O)—, —CH2—, —OCH2CH2O—, —O—, —S—, —P(O)2O—, —S(O)2—, —S(O)—, —C(O)NH—, —N═N—;
• and Y can be substituted by one or more R, with the proviso that the combination of each Y forms a chemically stable structure;
• each L1, L2, L3, L4, L5, L6 and L7 are independently selected from the group consisting of C1-C8 alkylene, C1-6 alkylene-O—C1-4 alkylene (—CH2—O—CH2—), C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, C6-C10 arylidene, 5-10 membered heteroarylidene, 3-12 membered heterocyclylene group, or a group selected from:
• —NH—, —C(O)—, —CH═CH—, —NH(CH2)—, —NHC(O)—, —CH2—, —OCH2CH2O—, —O—, —S—, —P(O)2O—, —S(O)2—, —S(O)—, —C(O)NH—, —N═N—, —C(O)NH(CH2)(1-4)-NHC(O)—;
• with the proviso that the combination of L1, L2, L3, L4, L5, L6 and L7 forms a stable divalent structure;
• and the Y, L1, L2, L3, L4, L5, L6 and L7 are optionally substituted by one or more R, and the R is selected from the group consisting of H, —OH, C1-C4 alkyl, halogen, cyano, nitro, —OR4, C1-6 haloalkyl, sulfonate group, formyl, carboxyl, —COOR4;
• with the proviso that each Y, L1, L2, L3, L4, L5, L6 and L7 together form a chemically stable structure;
• m, n, p, q, r, s and t are each independently selected from 0, 1, 2, 3, 4, 5, 6, 7 or 8;
• z is selected from the group consisting of 0, 1, 2, 3, 4, 5 or 6;
• preferably, z is selected from 1, 2 or 3.