| 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 R 1 and R 2 taken together form a group (D) or (G): wherein R 5 is hydrogen or C 1 -C 4 alkyl; R 3 and R 4 are independently hydrogen, C 1 -C 4 alkyl or C 1 -C 4 hydroxyalkyl; n is 0, 1 or 2; each of X is independently —O—, —S— or —NR 4 —; each of Y is independently —CH═ or —N═; R 7 and R 8 are independently hydrogen, halogen, hydroxy, C 1 -C 4 alkoxy, cyano, —NHCOOR 3 , —C(NH)NH 2 or —NR 3 R 4 ; 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; R 6 is a leaving group; A 1 is null or A; L 1 is hydrogen or L. |