AMATOXIN DERIVATIVES

摘要

The invention relates to tumour therapy. In one aspect, the present invention relates to conjugates of an amatoxin and a target-binding moiety, e.g. an antibody, connected by certain linkages, which are useful in the treatment of cancer and other disorders and diseases. In a further aspect the invention relates to pharmaceutical compositions comprising such conjugates.

主权项

1. An amatoxin of Formula I wherein: R1 is selected from C═O, C═S, C═NR6 and CR7R8; R2 is selected from S═O, SO2, and S; R3 is selected from NHR5 and OR5; R4 is selected from H, OR5, and OC1-6-alkyl; R6 is selected from C1-6-alkylene-R5, cycloalkylene-R5, heterocycloalkylene-R5, arylene-R5, and heteroarylene-R5; R7 and R8 are independently selected from H, C1-6-alkylene-R5, cycloalkylene-R5, heterocycloalkylene-R5, arylene-R5, and heteroarylene-R5; wherein: (i) each R5 is H; (ii) one of R5 is -Ln-X, wherein L is a linker, n is selected from 0 and 1, and X is a chemical moiety that can be coupled with a targeting moiety, and wherein the remaining R5 are H; or (iii) one of R5 is -Ln-X*—Y, wherein L is a linker, n is selected from 0 and 1, Y is a targeting moiety, and X* is a chemical moiety resulting from coupling X with a functional group of Y, and wherein the remaining R5 are H.