methyl 4-[(12aS)-9-[5-[[(12aS)-8-methoxy-6-oxo-12a,13-dihydroindolo[2,1-c][1,4]benzodiazepin-9-yl]oxy]pentoxy]-8-methoxy-6-oxo-12a,13-dihydro-12H-indolo[2,1-c][1,4]benzodiazepin-11-yl]-4-oxobutanoate | 1239587-21-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯二氮卓类
• 英文名称: methyl 4-[(12aS)-9-[5-[[(12aS)-8-methoxy-6-oxo-12a,13-dihydroindolo[2,1-c][1,4]benzodiazepin-9-yl]oxy]pentoxy]-8-methoxy-6-oxo-12a,13-dihydro-12H-indolo[2,1-c][1,4]benzodiazepin-11-yl]-4-oxobutanoate
• CAS: 1239587-21-3
• 化学式: C₄₄H₄₄N₄O₉
• 分子量: 772.855
• InChiKey: IJQOHAXUQUCNHT-KYJUHHDHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  57
• 可旋转键数：
  14
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.34
• 拓扑面积：
  137
• 氢给体数：
  0
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  (S)-9-((5-iodopentyl)oxy)-8-methoxy-12a,13-dihydro-6H-benzo[5,6][1,4]diazepino[1,2-a]indol-6-one 、 methyl 4-[(12aS)-9-hydroxy-8-methoxy-6-oxo-12a,13-dihydro-12H-indolo[2,1-c][1,4]benzodiazepin-11-yl]-4-oxobutanoate 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以66%的产率得到methyl 4-[(12aS)-9-[5-[[(12aS)-8-methoxy-6-oxo-12a,13-dihydroindolo[2,1-c][1,4]benzodiazepin-9-yl]oxy]pentoxy]-8-methoxy-6-oxo-12a,13-dihydro-12H-indolo[2,1-c][1,4]benzodiazepin-11-yl]-4-oxobutanoate
  参考文献：
  名称：

  [EN] NOVEL BENZODIAZEPINE DERIVATIVES
  [FR] NOUVEAUX DÉRIVÉS DE BENZODIAZÉPINE

  摘要：

  该发明涉及具有抗增殖活性的新型苯二氮䓬啶衍生物，更具体地涉及具有式(I)和(II)的新型苯二氮䓬啶化合物，其中二氮䓬啶环(B)与杂环环(CD)融合，其中杂环环是双环的或式(III)的化合物，其中二氮䓬啶环(B)与杂环环(C)融合，其中杂环环是单环的。该发明提供了这些化合物的细胞毒性二聚体。该发明还提供了单体和二聚体的结合物。该发明进一步提供了使用该发明的化合物或结合物抑制异常细胞生长或治疗哺乳动物增殖性疾病的有效组合物和方法。该发明还涉及使用该发明的化合物或结合物进行体外、原位和体内诊断或治疗哺乳动物细胞或相关病理条件的方法。

  公开号：

  WO2010091150A1

文献信息

• NOVEL BENZODIAZEPINE DERIVATIVES
  申请人：Li Wei

  公开号：US20100203007A1

  公开（公告）日：2010-08-12

  The invention relates to novel benzodiazepine derivatives with antiproliferative activity and more specifically to novel benzodiazepines of formula (I) and (II), in which the diazepine ring (B) is fused with a heterocyclic ring (CD), wherein the heterocyclic ring is bicyclic or a compound of formula (III), in which the diazepine ring (B) is fused with a heterocyclic ring (C), wherein the heterocyclic ring is monocyclic. The invention provides cytotoxic dimers of these compounds. The invention also provides conjugates of the monomers and the dimers. The invention further provides compositions and methods useful for inhibiting abnormal cell growth or treating a proliferative disorder in a mammal using the compounds or conjugates of the invention. The invention further relates to methods of using the compounds or conjugates for in vitro, in situ, and in vivo diagnosis or treatment of mammalian cells, or associated pathological conditions.

  本发明涉及具有抗增殖活性的新型苯二氮平衍生物，更具体地涉及公式（I）和（II）的新型苯二氮平，其中二氮平环（B）与杂环环（CD）融合，其中杂环环为双环或公式（III）的化合物，其中二氮平环（B）与杂环环（C）融合，其中杂环环为单环。本发明提供这些化合物的细胞毒性二聚体。本发明还提供单体和二聚体的结合物。本发明还提供使用该发明的化合物或结合物抑制异常细胞生长或治疗哺乳动物增殖性疾病的组合物和方法。本发明还涉及使用该化合物或结合物进行哺乳动物细胞的体外、原位和体内诊断或治疗，或相关病理条件的方法。
• CYTOTOXIC BENZODIAZEPINE DERIVATIVES
  申请人：Li Wei

  公开号：US20120244171A1

  公开（公告）日：2012-09-27

  The invention relates to novel benzodiazepine derivatives with antiproliferative activity and more specifically to novel benzodiazepine compounds of formula (I)-(VII). The invention also provides conjugates of the benzodiazepine compounds linked to a cell-binding agent. The invention further provides compositions and methods useful for inhibiting abnormal cell growth or treating a proliferative disorder in a mammal using the compounds or conjugates of the invention.

  本发明涉及具有抗增殖活性的新型苯二氮平衍生物，更具体地涉及公式（I）-（VII）的新型苯二氮平化合物。本发明还提供了与细胞结合剂连接的苯二氮平化合物的结合物。本发明还提供了使用该化合物或结合物抑制异常细胞生长或治疗哺乳动物增殖性疾病的组合物和方法。
• Cytotoxic benzodiazepine derivatives
  申请人：IMMUNOGEN, INC.

  公开号：US10179818B2

  公开（公告）日：2019-01-15

  The invention relates to novel benzodiazepine derivatives with antiproliferative activity and more specifically to novel benzodiazepine compounds of formula (I)-(VII). The invention also provides conjugates of the benzodiazepine compounds linked to a cell-binding agent. The invention further provides compositions and methods useful for inhibiting abnormal cell growth or treating a proliferative disorder in a mammal using the compounds or conjugates of the invention.

  本发明涉及具有抗增殖活性的新型苯并二氮杂卓衍生物，更具体地说，涉及式（I）-（VII）的新型苯并二氮杂卓化合物。本发明还提供了与细胞结合剂连接的苯二氮杂卓化合物共轭物。本发明进一步提供了使用本发明化合物或共轭物抑制哺乳动物异常细胞生长或治疗增殖性疾病的组合物和方法。
• Benzodiazepine derivatives
  申请人：ImmunoGen, Inc.

  公开号：US10208127B2

  公开（公告）日：2019-02-19

  The invention relates to novel benzodiazepine derivatives with antiproliferative activity and more specifically to novel benzodiazepines of formula (I) and (II), in which the diazepine ring (B) is fused with a heterocyclic ring (CD), wherein the heterocyclic ring is bicyclic or a compound of formula (III), in which the diazepine ring (B) is fused with a heterocyclic ring (C), wherein the heterocyclic ring is monocyclic. The invention provides cytotoxic dimers of these compounds. The invention also provides conjugates of the monomers and the dimers. The invention further provides compositions and methods useful for inhibiting abnormal cell growth or treating a proliferative disorder in a mammal using the compounds or conjugates of the invention. The invention further relates to methods of using the compounds or conjugates for in vitro, in situ, and in vivo diagnosis or treatment of mammalian cells, or associated pathological conditions.

  本发明涉及具有抗增殖活性的新型苯并二氮杂卓衍生物，更具体地说，涉及式(I)和(II)的新型苯并二氮杂卓，其中二氮杂卓环(B)与杂环(CD)融合，其中杂环为双环；或式(III)的化合物，其中二氮杂卓环(B)与杂环(C)融合，其中杂环为单环。本发明提供了这些化合物的细胞毒性二聚体。本发明还提供了单体和二聚体的共轭物。本发明进一步提供了使用本发明化合物或共轭物抑制哺乳动物异常细胞生长或治疗增殖性疾病的组合物和方法。本发明进一步涉及使用本发明化合物或共轭物体外、原位和体内诊断或治疗哺乳动物细胞或相关病理状况的方法。
• EP3666289A1
  申请人：——

  公开号：EP3666289A1

  公开（公告）日：2020-06-17