Novel hydrogel conjugates

A conjugate comprising a water-insoluble hydrogel Z, wherein said conjugate comprises a plurality of moieties -L2-L1-D covalently conjugated to Z,

• wherein
• each -D is drug moiety;
• each -L1- is independently a linker moiety to which -D is covalently and reversibly conjugated;
• each -L2- is independently either a chemical bond or a spacer moiety;
• Z is a PEG-based hydrogel comprising a plurality of backbone moieties that are crosslinked via crosslinker moieties —CL-, either directly or via a spacer moiety —SP— between a crosslinker moiety and —CL-, and wherein —CL- is of formula (A)
• wherein
• dashed lines indicate attachment to a backbone moiety or to a spacer moiety —SP—;
• —Y1— is of formula
• wherein the dashed line marked with the asterisk indicates attachment to -D1- and the unmarked dashed line indicates attachment to -D2-;
• —Y2— is of formula
• wherein the dashed line marked with the asterisk indicates attachment to -D4- and the unmarked dashed line indicates attachment to -D3-;
• -E1- is of formula
• wherein the dashed line marked with the asterisk indicates attachment to —(C═O)— and the unmarked dashed line indicates attachment to —O—;
• -E2- is of formula
• wherein the dashed line marked with the asterisk indicates attachment to -G1- and the unmarked dashed line indicates attachment to —(C═O)—;
• -G1- is of formula
• wherein the dashed line marked with the asterisk indicates attachment to —O— and the unmarked dashed line indicates attachment to -E2-;
• -G2- is of formula
• wherein the dashed line marked with the asterisk indicates attachment to —O— and the unmarked dashed line indicates attachment to —(C═O)—;
• -G3- is of formula
• wherein the dashed line marked with the asterisk indicates attachment to —O— and the unmarked dashed line indicates attachment to —(C═O)—;
• -D1-, -D2-, -D3-, -D4-, -D5- and -D6- are identical or different and each is independently of the others selected from the group comprising —O—, —NR11—, —N+R12R12a—, —S—, —(S═O)—, —(S(O)2)—, —C(O)—, —P(Q)R13—, —P(O)(OR13) and —CR14R14a—;
• —R1, —R1a, —R2, —R2a, —R3, —R3a, —R4, —R4a, —R5, —R5a, —R6, —R6a, —R7, —R7a, —R8, —R8a, —R9,
• —R9a, —R10, —R10a, —R11, —R12, —R12a, —R13, —R14 and —R14a are identical or different and each is independently of the others selected from the group consisting of —H and C1-6 alkyl;
• optionally, one or more of the pairs —R1/—R1a, —R2/—R2a, —R3/—R3a, —R4/—R4a, —R1/—R2, —R3/—R4, —R1a/—R2a, —R3a/—R4a, —R12/—R12a, and —R14/—R14a form a chemical bond or are joined together with the atom to which they are attached to form a C3-8 cycloalkyl or to form a ring A or are joined together with the atom to which they are attached to form a 4- to 7-membered heterocyclyl or 8- to 11-membered heterobicyclyl or adamantyl;
• A is selected from the group consisting of phenyl, naphthyl, indenyl, indanyl and tetralinyl;
• r1, r2, r5, r6, r13, r14, r15 and r16 are independently 0 or 1;
• r3, r4 are independently 0, 1, 2, 3, or 4, with the provision that r3+r4≥1;
• r7, r8, r9, r10, r11, r12 are independently 0, 1, 2, 3, or 4;
• r17, r18, r19, r20, r21 and r22 are independently 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10;
• s1, s2, s4, s5 are independently 1, 2, 3, 4, 5 or 6;
• and
• s3 ranges from 1 to 900.