C8, c8' linked 5-oxo-1,2,3,11a-tetrahydro-5h-pyrrolo[2,1-c][1,4] benzodiazepine dimers with 1h-pyrrole-dicarboxylic acid amide linkers and oligomeric analogs therof as well as related compounds for the treatment of proliferative diseases

摘要

Compounds of formula (I): PBD-A-Y-X-(Het)_na-L-(Het)_nb-L-(Het)_nc-T-(Het')_nd-L-(Het')_ne-L-(Het')_nf-X'-Y'- A'-PBD' and salts, solvates and chemically protected forms thereof, are disclosed wherein the PBD units have the formulae (PBD) (PBD') with the bonds at the 8 position on each molecule bond to the A and A' groups respectively; A is selected from O, S, NH or a single bond, and each Het and Het' is respectively an amino-heteroarylene-carbonyl group; X and X' are both either NH or C (-O)-Q-C(-O)- wherein Q is a divalent group such that HY-R; in a second aspectm the invention comprises compounds of the general formula (II): PBD-A-Y-X-(Het)_ng-[L-(Het)_nh]_nj-X'-Y'-A'-PBD'. Wherein: PBD and PBD' are as defined above, X and X' are either NH and C(-O) respectively or C(O) and NH respectively; the other substitutents are defined in the claims. Further aspects of the present invention relate to their use in the manufacture of a medicament for the treatment of a proliferative disease.