| abstract |
The invention relates to new functionalized thieno-indole derivatives of formula (I) or (II) which have cytotoxic activity and are useful in treating diseases such as cancer and cellular proliferation disorders. The invention also relates to the use of these functionalized thieno-indole derivatives in the preparation of conjugates. Formula (I) or (II) wherein R1 and R2 taken together form a group (D) or (G): wherein R5 is hydrogen or C1-C4 alkyl; R3 and R4 are independently hydrogen, C1-C4 alkyl or C1-C4 hydroxyalkyi; n is 0, 1 or 2; each of X is independently -O-, -S- or -NR4-; each of Y is independently -CH = or -N=; R7 and R8 are independently hydrogen, halogen, hydroxy, C1-C4 alkoxy, cyano, -NHCOOR3, -C(NH)NH2 or -NR3R4; A is -O-, -NH- or -CO-; L is null or a conditionally-cleavable moiety; W is null or a self-immolative moiety comprising one or more self-immolative groups; Z is null or a peptidic, non peptidic or hybrid peptidic and non peptidic linker; RM is null or a reactive moiety; R6 is a leaving group; A1 is null or A; L1 is hydrogen or L. |