5-((4-((S)-2-((S)-2-amino-3-methylbutanamido)propanamido)benzyl)amino)-6-(7-amino-6-methoxy-5,8-dioxo-5,8-dihydroquinolin-2-yl)-4-(2-hydroxy-3,4-dimethoxyphenyl)-3-methylpicolinic acid | 1166834-75-8

• 分子结构分类: 有机化合物 - 有机杂环化合物
• 英文名称: 5-((4-((S)-2-((S)-2-amino-3-methylbutanamido)propanamido)benzyl)amino)-6-(7-amino-6-methoxy-5,8-dioxo-5,8-dihydroquinolin-2-yl)-4-(2-hydroxy-3,4-dimethoxyphenyl)-3-methylpicolinic acid
• CAS: 1166834-75-8
• 化学式: C₄₀H₄₃N₇O₁₀
• 分子量: 781.822
• InChiKey: MMTYQQNYFOGCLL-PPHZAIPVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.77
• 重原子数：
  57.0
• 可旋转键数：
  14.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  267.41
• 氢给体数：
  7.0
• 氢受体数：
  14.0

反应信息

• 作为反应物：
  描述：

  6-(马来酰亚胺基)己酸琥珀酰亚胺酯 、 5-((4-((S)-2-((S)-2-amino-3-methylbutanamido)propanamido)benzyl)amino)-6-(7-amino-6-methoxy-5,8-dioxo-5,8-dihydroquinolin-2-yl)-4-(2-hydroxy-3,4-dimethoxyphenyl)-3-methylpicolinic acid 在 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以86%的产率得到6-(7-amino-6-methoxy-5,8-dioxo-5,8-dihydroquinolin-2-yl)-5-((4-((S)-2-((S)-2-(6-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)hexanamido)-3-methylbutanamido)propanamido)benzyl)amino)-4-(2-hydroxy-3,4-dimethoxyphenyl)-3-methylpicolinic acid
  参考文献：
  名称：

  Novel immunoconjugates comprised of streptonigrin and 17-amino-geldanamycin attached via a dipeptide-p-aminobenzyl-amine linker system

  摘要：

  Cytotoxic agents streptonigrin and 17-amino-geldanamycin were linked to monoclonal antibodies (mAbs), forming antibody-drug conjugates (ADCs) for antigen-mediated targeting to cancer cells. The drugs were conjugated with a linker construct that is labile to lysosomal proteases and incorporates a valine-alanine-p-aminobenzyl (PAB)-amino linkage for direct attachment to the electron-deficient amine functional groups present in both drugs. The resulting ADCs release drug following internalization into antigen-positive cancer cells. The drug linkers were conjugated to mAbs cAC10 (anti-CD30) and h1F6 (anti-CD70) via alkylation of reduced interchain disulfides to give ADCs loaded with 4 drugs/mAb. The streptonigrin ADCs were potent and immunologically specific on a panel of cancer cell lines in vitro and in a Hodgkin lymphoma xenograft model. We conclude that streptonigrin ADCs are candidates for further research, and that the novel linker system used to make them is well-suited for the conjugation of cytotoxic agents containing electron-deficient amine functional groups. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.03.145
• 作为产物：
  描述：

  在 哌啶 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以100%的产率得到5-((4-((S)-2-((S)-2-amino-3-methylbutanamido)propanamido)benzyl)amino)-6-(7-amino-6-methoxy-5,8-dioxo-5,8-dihydroquinolin-2-yl)-4-(2-hydroxy-3,4-dimethoxyphenyl)-3-methylpicolinic acid
  参考文献：
  名称：

  Novel immunoconjugates comprised of streptonigrin and 17-amino-geldanamycin attached via a dipeptide-p-aminobenzyl-amine linker system

  摘要：

  Cytotoxic agents streptonigrin and 17-amino-geldanamycin were linked to monoclonal antibodies (mAbs), forming antibody-drug conjugates (ADCs) for antigen-mediated targeting to cancer cells. The drugs were conjugated with a linker construct that is labile to lysosomal proteases and incorporates a valine-alanine-p-aminobenzyl (PAB)-amino linkage for direct attachment to the electron-deficient amine functional groups present in both drugs. The resulting ADCs release drug following internalization into antigen-positive cancer cells. The drug linkers were conjugated to mAbs cAC10 (anti-CD30) and h1F6 (anti-CD70) via alkylation of reduced interchain disulfides to give ADCs loaded with 4 drugs/mAb. The streptonigrin ADCs were potent and immunologically specific on a panel of cancer cell lines in vitro and in a Hodgkin lymphoma xenograft model. We conclude that streptonigrin ADCs are candidates for further research, and that the novel linker system used to make them is well-suited for the conjugation of cytotoxic agents containing electron-deficient amine functional groups. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.03.145