(S)-2-(3-((R)-(1-benzyl-4-(2,5-difluorophenyl)-1H-imidazol-2-yl)(tetrahydro-2H-pyran-4-yl)methyl)-3-(((3S,4R)-4-fluoropyrrolidin-3-yl)methyl)ureido)propyl (2-(2-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)ethoxy)ethyl)carbamate

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: (S)-2-(3-((R)-(1-benzyl-4-(2,5-difluorophenyl)-1H-imidazol-2-yl)(tetrahydro-2H-pyran-4-yl)methyl)-3-(((3S,4R)-4-fluoropyrrolidin-3-yl)methyl)ureido)propyl (2-(2-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)ethoxy)ethyl)carbamate
• 英文别名: [(2S)-2-[[[(R)-[1-benzyl-4-(2,5-difluorophenyl)imidazol-2-yl]-(oxan-4-yl)methyl]-[[(3S,4R)-4-fluoropyrrolidin-3-yl]methyl]carbamoyl]amino]propyl] N-[2-[2-(2,5-dioxopyrrol-1-yl)ethoxy]ethyl]carbamate
• 化学式: C₄₀H₄₈F₃N₇O₇
• 分子量: 795.859
• InChiKey: FQNPWPHAFYTAJG-GQNRCETCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  57
• 可旋转键数：
  18
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  156
• 氢给体数：
  3
• 氢受体数：
  12

反应信息

• 作为产物：
  描述：

  (3R,4R)-tert-butyl 3-((S)-2-((R)-(1-benzyl-4-(2,5-difluorophenyl)-1H-imidazol-2-yl)(tetrahydro-2H-pyran-4-yl)methyl)-14-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)-5-methyl-3,8-dioxo-7,12-dioxa-2,4,9-triazatetradecyl)-4-fluoropyrrolidine-1-carboxylate 在 三氟乙酸 作用下， 以 乙腈 为溶剂， 以67%的产率得到(S)-2-(3-((R)-(1-benzyl-4-(2,5-difluorophenyl)-1H-imidazol-2-yl)(tetrahydro-2H-pyran-4-yl)methyl)-3-(((3S,4R)-4-fluoropyrrolidin-3-yl)methyl)ureido)propyl (2-(2-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)ethoxy)ethyl)carbamate
  参考文献：
  名称：

  [EN] CELL PROLIFERATION INHIBITORS AND CONJUGATES THEREOF
  [FR] INHIBITEURS DE LA PROLIFÉRATION CELLULAIRE ET LEURS CONJUGUÉS

  摘要：

  本发明公开了包含Eg5抑制剂的免疫偶联物，该抑制剂与抗原结合部分如抗体相连，用于治疗细胞增殖紊乱。还公开了新颖的Eg5抑制剂，可以单独使用或作为免疫偶联物的一部分来治疗细胞增殖紊乱。Eg5抑制剂包括如本文所述的这种化合物的化合物：[在此插入第68页的最后一个结构]本发明进一步提供了包含这些化合物和免疫偶联物的药物组合物，可选地包括治疗共剂，以及使用这些化合物、偶联物和组合物来治疗细胞增殖紊乱的方法。

  公开号：

  WO2014151030A1

文献信息

• CELL PROLIFERATION INHIBITORS AND CONJUGATES THEREOF
  申请人：Barsanti Paul A.

  公开号：US20140322247A1

  公开（公告）日：2014-10-30

  Disclosed herein are immunoconjugates comprising an inhibitor of Eg5 linked to an antigen binding moiety such as an antibody, that are useful for treating cell proliferative disorders. Also disclosed are novel inhibitors of Eg5 that can be used either alone or as part of an immunoconjugate to treat cell proliferation disorders. The Eg5 inhibitors include compounds of this formula as described herein: The invention further provides pharmaceutical compositions comprising these compounds and immunoconjugates, and compositions comprising the immunoconjugates or compounds with a therapeutic co-agent, and methods to use these compounds, conjugates and compositions for treating cell proliferation disorders.

  本文披露了一种包含Eg5抑制剂和抗原结合部分（如抗体）的免疫结合物，用于治疗细胞增殖性疾病。还披露了新型的Eg5抑制剂，可单独使用或作为免疫结合物的一部分用于治疗细胞增殖性疾病。Eg5抑制剂包括本文所述的这种化合物：进一步提供了包含这些化合物和免疫结合物的药物组合物，以及包含免疫结合物或化合物与治疗协同剂的组合物，以及使用这些化合物、结合物和组合物治疗细胞增殖性疾病的方法。
• CKIT antibody drug conjugates
  申请人：Novartis AG

  公开号：US10786578B2

  公开（公告）日：2020-09-29

  The present invention relates to anti-cKIT antibodies, antibody fragments, antibody drug conjugates, and their uses for the treatment of cancer.

  本发明涉及抗 KIT 抗体、抗体片段、抗体药物共轭物及其治疗癌症的用途。
• SPECIFIC SITES FOR MODIFYING ANTIBODIES TO MAKE IMMUNOCONJUGATES
  申请人：NOVARTIS AG

  公开号：US20170021033A1

  公开（公告）日：2017-01-26

  The present application provides specific sites for modifying antibodies or antibody fragments by replacing at least one native amino acid in the constant region of a parental antibody or antibody fragment with cysteine, which can be used as a site of attachment for a payload or linker-payload combination. In one embodiment, the antibodies are modified with cysteines at positions 152 and 375 of the heavy chain constant region, as defined by EU numbering format. In another embodiment, the antibodies are modified with cysteines at position 360 of the heavy chain constant region, and position 107 of the kappa light chain constant region, as defined by EU numbering format.
• CKIT ANTIBODY DRUG CONJUGATES
  申请人：Novartis AG

  公开号：US20180193475A1

  公开（公告）日：2018-07-12

  The present invention relates to anti-cKIT antibodies, antibody fragments, antibody drug conjugates, and their uses for the treatment of cancer.
• US9498540B2
  申请人：——

  公开号：US9498540B2

  公开（公告）日：2016-11-22