- 专利标题: FUNCTIONALIZED THIENO-INDOLE DERIVATIVES FOR THE TREATMENT OF CANCER
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申请号: EP13713180.1申请日: 2013-03-28
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公开(公告)号: EP2836493B1公开(公告)日: 2018-06-20
- 发明人: BERIA, Italo , CARUSO, Michele , LUPI, Vittoria , ORSINI, Paolo , SALSA, Matteo
- 申请人: Nerviano Medical Sciences S.r.l.
- 申请人地址: 11 Viale Pasteur, 10 P.O. Box 11 20014 Nerviano (MI) IT
- 专利权人: Nerviano Medical Sciences S.r.l.
- 当前专利权人: Nerviano Medical Sciences S.r.l.
- 当前专利权人地址: 11 Viale Pasteur, 10 P.O. Box 11 20014 Nerviano (MI) IT
- 优先权: EP12163437 20120405
- 国际公布: WO2013149946 20131010
- 主分类号: C07D495/04
- IPC分类号: C07D495/04 ; A61K31/407 ; A61P35/00
摘要:
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 hydroxyalkyl; 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.
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