| 主权项 |
1. A prodrug or a pharmaceutically acceptable salt thereof comprising an exendin linker conjugate D-L1 and a hydrogel Z with backbone moieties of formula C-(A-Hyp)4, wherein
each A is independently selected from the formula —(CH2)n1(OCH2CH2)nX—,
wherein:
n1 is 1 or 2;n is an integer ranging from 5 to 50; andX is an amide linkage linking A and Hyp;each Hyp is independently selected from hyperbranched polypeptides comprising lysine;the backbone moieties are crosslinked by poly(ethylene glycol)-based crosslinker moieties, comprising m ethylene glycol units, wherein m is an integer ranging from 3-100, and terminated by at least two hydrolytically degradable bonds; a linker L2 connected to a backbone moiety, wherein:
L2 is a single chemical bond or is a C1-20 alkyl chain, which is optionally interrupted by one or more groups independently selected from —O— and C(O)N(R3aa) and is optionally substituted with one or more groups independently selected from OH and C(O)N(R3aaR3aaa), wherein R3aa and R3aaa are independently selected from the group consisting of H and C1-4 alkyl; andL2 is attached to Z via a terminal group selected from the group consisting of wherein L2 is attached to the sulfur atom in structure X and Z is attached to the nitrogen atom in structure X or L2 is attached to the nitrogen atom in structure XI and Z is attached to the sulfur atom in structure XI; and D is an exendin and -L1 is of formula (I), wherein the dashed line indicates attachment of L1 to one of the amino groups of the exendin through an amide bond; R1 is selected from C1-4 alkyl; R2 and R2a are independently selected from the group consisting of H and C1-4 alkyl; L1 is substituted with one L2-Z, wherein L2-Z replaces one of the hydrogen atoms in R1, R2 or R2a, provided that the hydrogens marked with the asterisks in formula (I) are not replaced. |
