Intermediate compound for the preparation of conjugates comprising auristatin derivatives and a linker

摘要

A conjugate having the formula: LU-DF or a pharmaceutically acceptable salt thereof, wherein: LU- is a linker unit comprising a functional group capable of binding to a ligand or an antibody, and DF is a group having the following formula: ** Formula ** wherein: independently at each location: R2 is selected from H and C1-C8 alkyl; R3 is selected from H, C1-C8 alkyl, C3-C8 carbocycle, aryl, C1-C8 alkylaryl, C1-C8 alkyl- (C3-C8 carbocycle), C3-C8 heterocycle and C1-C8 alkyl- (C3-C8 heterocycle) ); R4 is selected from H, C1-C8 alkyl, C3-C8 carbocycle, aryl, C1-C8 alkylaryl, C1-C8 alkyl- (C3-C8 carbocycle), C3-C8 heterocycle and C1-C8 alkyl- (C3-C8 heterocycle) ); R5 is selected from H and methyl; or: R4 and R5 together form a carbocyclic ring having the formula - (CRaRb) n-, wherein Ra and Rb are independently selected from H, C1-C8 alkyl and C3-C8 carbocycle and n is selected from 2, 3, 4, 5 and 6; R6 is selected from H and C1-C8 alkyl; R7 is selected from H, C1-C8 alkyl, C3-C8 carbocycle, aryl, C1-C8 alkylaryl, C1-C8 alkyl- (C3-C8 carbocycle), 3 C3-C8 heterocycle and C1-C8 alkyl- (C3- heterocycle) C8); each R8 is independently selected from H, OH, C1-C8 alkyl, C3-C8 carbocycle and O- (C1-C8 alkyl); R9 is selected from H and C1-C8 alkyl; R10 is selected from aryl and C3-C8 heterocycle; Z is O, S, NH or NR 12, wherein R 12 is C 1 -C 8 alkyl; R11 is selected from H, C1-C20 alkyl, - (R13O) m-R14 and - (R13O) m-CH (R15) 2; m is an integer comprised from 1 to 1000; R 13 is C 2 -C 8 alkyl; R14 is H or C1-C8 alkyl; each occurrence of R15 is independently H, COOH, - (CH2) n-N (R16) 2, - (CH2) n- SO3H or - (CH2) n-SO3- C1-C8 alkyl; each occurrence of R16 is independently H, C1-C8 alkyl or - (CH2) n -COOH; and n is an integer between 0 and 6.