New cryptophycin compounds and conjugates, their preparation and therapeutic use

摘要

Cryptophycin compound of formula (I): ** Formula ** wherein: - R1 represents a (C1-C6) alkyl group; - R2 and R3 represent, independently of each other, a hydrogen atom or a (C1-C6) alkyl group; or alternatively R2 and R3 form together with the carbon atom to which they are attached a cycloalkyl (C3-C6) or hetercycloalkyl (C3-C6) group; - R4 and R5 represent, independently of each other, a hydrogen atom or a (C1-C6) -alkyl group or a (C1-C6) -alkyl group -NH (R12) or a (C1-C6) -alkyl group -OH or a (C1-C6) -alkyl group or a (C1-C6) -CO2H-alkyl group; or alternatively R4 and R5 form together with the carbon atom to which they are attached a cycloalkyl (C3-C6) or hetercycloalkyl (C3-C6) group; - R6 represents a hydrogen atom or a (C1-C6) alkyl group; - R7 and R8 represent, independently of each other, a hydrogen atom or a (C1-C6) alkyl group or a (C1-C6) -CO2H alkyl group or a (C1-C6) -alkyl (C1-C6) alkyl group 2; or alternatively R7 and R8 form together with the carbon atom to which they are attached a cycloalkyl (C3-C6) group or a hetercycloalkyl (C3-C6) group; - R9 represents one or more substituents of the phenyl nucleus chosen, independently of each other, from: a hydrogen atom, -OH, (C1-C4) alkoxy, a halogen atom, -NH2, -NHalkyl (C1-C6) or -C1-C6alkyl 2 or -NH-cycloalkyl (C1-C6) or heterocycloalkyl (C3-C6); - R10 represents at least one substituent of the phenyl nucleus chosen from a hydrogen atom and (C1-C4) alkyl; - W represents - (C1-C6) -alkyl-NH (R11), - (C1-C6) -alkyl -OH, - (C1-C6) -alkyl -SH, - CO2H or C (= O) NH2; - (C1-C6) alkyl-CO2H or (C1-C6) -C (= O) NH2 alkyl; or - (C1-C6) -alkyl-N3. - R11 and R12 represent, independently of each other, a hydrogen atom or a (C1-C6) alkyl group.