Effector conjugates, methods for their preparation and their pharmaceutical use

Conjugates of general formula (I):

• 9
• in which
• R1a, R1b, independently of one another, are hydrogen, C1-C10 alkyl, aryl, aralkyl, or together a —(CH2)m group, in which m is 2 to 5,
• R2a, R2b, independently of one another, are hydrogen, C1-C10 alkyl, aryl, aralkyl, or together a —(CH2)n group, in which n is 2 to 5, or C2-C10 alkenyl, or C2-C10 alkinyl,
• R3 is hydrogen, C1-C10 alkyl, aryl or aralkyl, and
• R4a, R4b, independently of one another, are hydrogen, C1-C10 alkyl, aryl, aralkyl, or together a —(CH2)p group, in which p is 2 to 5,
• R5 is hydrogen, C1-C10 alkyl, aryl, aralkyl, CO2H, CO2alkyl, CH2OH, CH2Oalkyl, CH2Oacyl, CN, CH2NH2, CH2N(alkyl, acyl)1,2, or CH2Hal,
• Hal is a halogen atom,
• R6, R7, in each case, are hydrogen, or together an additional bond or together an oxygen atom, or together an NH group, or together an N-alkyl group, or together a CH2 group, and
• G is an oxygen atom or CH2,
• D—E is a group H2C—CH2, HC═CH, C≡C, CH(OH)—CH(OH), CH(OH)—CH2, CH2—CH(OH),
• 10
• O—CH2, or, if G represents a CH2 group, is CH2—O,
• W is a group C(═X)R8, or a bi- or tricyclic aromatic or heteroaromatic radical,
• L3 is hydrogen, or, if a radical in W contains a hydroxyl group, forms a group O—L4 with the latter, or, if a radical in W contains an amino group, forms a group NR25—L4 with the latter,
• R25 is hydrogen or C1-C10 alkyl,
• X is an oxygen atom, or two OR20 groups, or a C2-C10 alkylenedioxy group, which should be straight-chain or branched, or H/OR9, or a CR10R11 group,
• R8 is hydrogen, C1-C10 alkyl, aryl, aralkyl, halogen or CN, and
• R9 is hydrogen or a protective group PGX,
• R10, R11, in each case independently of one another, are hydrogen, C1-C20 alkyl, aryl, or aralkyl, or together with a methylene carbon atom form a 5- to 7-membered carbocyclic ring,
• Z can represent oxygen or H/OR12,
• R12 can represent hydrogen or a protective group PGZ,
• A—Y can represent a group O—C(═O), O—CH2, CH2—C(═O), NR21—C(═O) or NR21—SO2,
• R20 can represent C1-C20 alkyl,
• R21 can represent a hydrogen atom or C1-C10 alkyl,
• PGX, PGY, and PGZ can represent a protective group PG, and
• L1, L2, L4, independently of one another, can represent hydrogen, a group C(═O)Cl, a group C(═S)Cl, a group PGY or a linker-recognition unit of general formula (III);
• with the condition that at least one substituent L1, L2 or L4 represents a linker-recognition unit of general formula (III);
• the linker-recognition unit of general formula (III) has the following structure,
• 11
• in which
• R22a, R22b, independently of one another, can represent hydrogen, C1-C20 alkyl, C1-C20 acyl, C1-C20 acyloxy, aryl, aralkyl, hydroxy, alkoxy, CO2H, CO2alkyl, halogen, CN, NO2, NH2, or N3,
• U can represent —C(═O)NR23—, —C(═S)NR23—, —C(═O)NR23—CH2—, —C(═S)NR23—CH2—, —C(═O)O—, —C(═S)O—, —C(═O)O—CH2—, —C(═S)O—CH2—,
• R23 can represent hydrogen or C1-C10 alkyl, and
• EG is a recognition unit of general formula (IV):
• 12
• in which
• R24 can represent a group CH2OPG4 or a group CO2R26,
• PG1, PG2, PG3, and PG4, independently of one another, can represent hydrogen or a protective group PG,
• R26 can represent hydrogen, C1-C20 alkyl, C1-C20 alkenyl, C4-C7 cycloalkyl, which can contain an oxygen atom, aryl, aralkyl, tris(C1-C20 alkyl)silyl, bis(C1-C20 alkyl)-arylsilyl, (C1-C20 alkyl)-diarylsilyl, or tris(aralkyl)-silyl,
• as a uniform isomer or a mixture of different isomers and/or as a pharmaceutically acceptable salt thereof.