Prodrugs of cytotoxic active agents having enzymatically cleavable groups

A compound of formula Ia:

• wherein
• m is 0 to 2;
• n is 0 or 1;
• X is —C(═O)—NH2 or —COOH,
• La is a self-immolative linker,
• A1 is a radical which derives from one of the amino acids Gly, Pro, Ala, Val, Nva, Leu, Ile, Met, Phe, Tyr, Trp, Ser, Thr, Cys, Asn, Gln, Asp, Glu, Lys, Arg, citrulline, His, or one of the respective N-alkyl amino acids,
• A2 is a radical which derives from one of the amino acids D-Ala, D-Pro, D-Val, D-Nva, D-Leu, D-Ile, D-Met, D-Phe, D-Tyr, D-Trp, D-Ser, D-Thr, D-Cys, D-Asn, D-Gln, D-Asp, D-Glu, D-Lys, D-Arg, D-citrulline, D-His, or one of the respective N-alkyl amino acids,
• R2a is —H or C1-C3-alkyl,
• or
• R2a is the bond to the methylene group of the proline ring if A2 is a radical which derives from D-Pro,
• D is -D1-(Lb)o-(LIG),
• D1 is a cytotoxic drug,
• LIG is an antibody or antigen binding fragment thereof which, after binding to a target molecule of a tumour cell, is internalized by the tumour cell and processed intracellularly,
• Lb is a linker,
• o is 0 or 1,
• R is Z1—(C═O)q-,
• q is 0 or 1,
• Z1 is a C1-10-alkyl, C5-10-aryl, C6-10-aralkyl, C5-10-heteroalkyl, C1-10-alkyl-O—C6-10-aryl, C5-10-heterocycloalkyl, heteroaryl, heteroarylalkyl, C5-10-heteroarylalkoxy, C1-10-alkoxy, C6-10-aryl-C1-10-alkyloxy, C6-10-aryloxy-C6-10-aralkoxy-, C5-10-heteroalkoxy, C1-10-alkyl-O-C6-10-aryloxy- or C5-10-heterocycloalkoxy group, each of which may be mono- or polysubstituted by —NH2, —C(═O)—, —NH-alkyl, —N(alkyl)2, —NH—C(═O)-alkyl, —N(alkyl)-C(═O)-alkyl, —S(═O)3—H, —S(═O)2—NH2, —S(═O)2-N(alkyl)2, —COOH, —C(═O)NH2, —C(═O)—N(alkyl)2 or —OH, or
• Z1 is —H or a —(CH2)0-1-Ox-(CH2CH2O)v-R1a group,
• x is 0 or 1,
• v is a number from 1 to 20,
• R1a is —H, -alkyl, —CH2—COOH, —CH2—CH2—COOH, or —CH2—CH2—NH2.