Prodrugs comprising a pyroglutamate linker

A conjugate D-L1 or a pharmaceutically acceptable salt thereof,

• wherein
• -D is a primary or secondary amine-comprising biologically active moiety;
• and
• -L1 is represented by formula (I):
• wherein:
• the dashed line indicates attachment to the primary or secondary amine of the biologically active moiety;
• —X1 is selected from the group consisting of —C(R5R5a)—, —O—, —N(R5)—, and —S—;
• —R4 is methyl;
• —R1, R1a, R2, R3, R4a, R5, and —R5a are independently of each other selected from the group consisting of —H, C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl, wherein:
• C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl are optionally substituted with one or more R6, which are the same or different;
• and
• C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl are optionally interrupted by one or more groups selected from the group consisting of —T—, —C(O)O—, —O—, —C(O)—, —C(O)N(R7)—, —S(O)2N(R7)—, —S(O)N(R7)—, —S(O)2—, —S(O)—, —N(R7)S(O)2N(R7a)—, —S—, —N(R7)—, —OC(OR7)(R7a)—, —N(R7)C(O)N(R7a)—, and —OC(O)N(R7)—, provided that the nitrogen marked with the asterisk is connected to —R2 through an SP3-hybridized carbon atom of —R2;
• each T is independently of each other selected from the group consisting of phenyl, naphthyl, indenyl, indenyl, tetralinyl, C3-10 cycloalkyl, 3- to 10-membered heterocyclyl, and 8- to 11-membered heterobicyclyl, wherein:
• each T is independently optionally substituted with one or more R6, which are the same or different;
• each —R6, —R7, and —R7a is independently selected from the group consisting of —H and C1-6 alkyl, wherein:
• C1-6 alkyl is optionally substituted with one or more halogen, which are the same or different;
• ═Y1 is selected from ═O and ═NR5;
• optionally, one or more of the pairs —R1/—R1a, —R2/—R3, —R5/—R5a, and —R4/—R4a are joined together with the atom to which they are attached to form a C3-10 cycloalkyl, 3- to 10-membered heterocyclyl or a 8- to 11-membered heterobicyclyl;
• optionally, one or more of the pairs —R1/—R2, —R1/—R5a, —R1a/—R2, —R1a/—R3, —R1a/—R5, —R1a/—R5a, —R2/—R5, —R2/—R5a, —R3/—R5, —R3/—R5a are joined together with the atoms to which they are attached to form a ring —A—, where:
• —A—is selected from the group consisting of phenyl, naphthyl, indenyl, indanyl, tetralinyl, C3-10 cycloalkyl, 3- to 10-membered heterocyclyl, and 8- to 11-membered heterobicyclyl;
• wherein -L1 is substituted with one to five moieties -L2-Z, wherein the one to five hydrogens for substitutions are given by —R1, —R1a, —R2, —R3, —R4a, —R5, —R5a, —R6 or —R7 of -L1, wherein:
• -L2- is a single chemical bond or a spacer moiety;
• and
• -Z is a carrier moiety.