tert-butyl (2S)-3-[[4-[2-[6-(methylamino)pyridin-2-yl]ethyl]benzoyl]amino]-2-[[4-[3-[2-[2-[(2-methylpropan-2-yl)oxycarbonylamino]ethoxy]ethoxy]propyl]phenyl]sulfonylamino]propanoate | 801239-54-3

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: tert-butyl (2S)-3-[[4-[2-[6-(methylamino)pyridin-2-yl]ethyl]benzoyl]amino]-2-[[4-[3-[2-[2-[(2-methylpropan-2-yl)oxycarbonylamino]ethoxy]ethoxy]propyl]phenyl]sulfonylamino]propanoate
• CAS: 801239-54-3
• 化学式: C₄₀H₅₇N₅O₉S
• 分子量: 783.987
• InChiKey: PZNCUUCKLSPBEO-UMSFTDKQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  55
• 可旋转键数：
  25
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  192
• 氢给体数：
  4
• 氢受体数：
  12

反应信息

• 作为反应物：
  描述：

  tert-butyl (2S)-3-[[4-[2-[6-(methylamino)pyridin-2-yl]ethyl]benzoyl]amino]-2-[[4-[3-[2-[2-[(2-methylpropan-2-yl)oxycarbonylamino]ethoxy]ethoxy]propyl]phenyl]sulfonylamino]propanoate 在 苯甲醚 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 生成
  参考文献：
  名称：

  Use of Retro-Aldol Reaction to Generate Reactive Vinyl Ketone for Attachment to Antibody Molecules by Michael Addition Reaction for Use in Immunostaining and Immunotargeting

  摘要：

  本发明涉及一种制备化学程序化抗体的方法，包括以下步骤：(1)将信号模块共价连接到前适配体上，与催化部分子反应，所述催化部分子选自催化抗体和催化抗体的Fab片段，其中前适配体中包含一种通过催化部分子催化反应激活为反应性部分子的前体；(2)将反应性部分子与催化部分子活性位点的氨基酸残基侧链交联，以制备化学程序化抗体。本发明还涵盖了通过这些方法形成的化学程序化抗体、它们的使用方法、制药组合物，以及包括它们的前适配体和共轭物。化学程序化抗体对于治疗癌症，特别是转移性癌症具有用处。

  公开号：

  US20080213249A1
• 作为产物：
  描述：

  6-溴-2-甲基氨基吡啶 在 palladium on activated charcoal N-甲基吗啉 、 bis-triphenylphosphine-palladium(II) chloride 、 sodium hydroxide 、 copper(l) iodide 、 氢气 、 1-羟基苯并三唑 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 64.0h， 生成 tert-butyl (2S)-3-[[4-[2-[6-(methylamino)pyridin-2-yl]ethyl]benzoyl]amino]-2-[[4-[3-[2-[2-[(2-methylpropan-2-yl)oxycarbonylamino]ethoxy]ethoxy]propyl]phenyl]sulfonylamino]propanoate
  参考文献：
  名称：

  Chemical Adaptor Immunotherapy:  Design, Synthesis, and Evaluation of Novel Integrin-Targeting Devices

  摘要：

  A series of beta-diketone derivatives of RGD peptidornimetics that selectively bind to alphabbeta3 and alphavbeta5 integrins were synthesized and covalently docked to the reactive lysine residues of monoclonal aldolase antibody 38C2. The resulting targeting devices strongly and selectively bound to human cancer cells expressing integrins alphavbeta3 and alphavbeta5 as analyzed by flow cytometry. In vitro and in vivo studies revealed that these novel integrin-targeting devices efficiently inhibit tumor growth. Thus, the combination of beta-diketone derivatives of RGD peptidomimetics that target cell surface integrins alphavbeta3 and alphavbeta5 with monoclonal aldolase antibodies through formation of a covalent bond of defined stoichiometry holds promise as a new approach to cancer therapy.

  DOI：

  10.1021/jm049666k

文献信息

• Chemical Adaptor Immunotherapy:  Design, Synthesis, and Evaluation of Novel Integrin-Targeting Devices
  作者：Lian-Sheng Li、Christoph Rader、Masayuki Matsushita、Sanjib Das、Carlos F. Barbas、Richard A. Lerner、Subhash C. Sinha

  DOI：10.1021/jm049666k

  日期：2004.11.1

  A series of beta-diketone derivatives of RGD peptidornimetics that selectively bind to alphabbeta3 and alphavbeta5 integrins were synthesized and covalently docked to the reactive lysine residues of monoclonal aldolase antibody 38C2. The resulting targeting devices strongly and selectively bound to human cancer cells expressing integrins alphavbeta3 and alphavbeta5 as analyzed by flow cytometry. In vitro and in vivo studies revealed that these novel integrin-targeting devices efficiently inhibit tumor growth. Thus, the combination of beta-diketone derivatives of RGD peptidomimetics that target cell surface integrins alphavbeta3 and alphavbeta5 with monoclonal aldolase antibodies through formation of a covalent bond of defined stoichiometry holds promise as a new approach to cancer therapy.
• Use of Retro-Aldol Reaction to Generate Reactive Vinyl Ketone for Attachment to Antibody Molecules by Michael Addition Reaction for Use in Immunostaining and Immunotargeting
  申请人：Sinha Subhash C.

  公开号：US20080213249A1

  公开（公告）日：2008-09-04

  The present invention is directed to methods for formation of a chemically programmed antibody comprising the steps of: (1) reacting a conjugate comprising a signal module covalently linked to a proadapter with a catalytic moiety selected from the group consisting of a catalytic antibody and a Fab fragment of a catalytic antibody, wherein the proadapter includes therein a precursor to a reactive moiety activated to a reactive moiety by a reaction catalyzed by the catalytic moiety; and (2) crosslinking the reactive moiety to a side chain of an amino acid residue in the active site of the catalytic moiety to produce the chemically programmed antibody. The invention also encompasses chemically programmed antibodies formed by these methods, methods for their use, and pharmaceutical compositions, as well as proadaptors and conjugates including them. Chemically programmed antibodies are useful for the treatment of cancer, particularly in metastasis.

  本发明涉及一种制备化学程序化抗体的方法，包括以下步骤：(1)将信号模块共价连接到前适配体上，与催化部分子反应，所述催化部分子选自催化抗体和催化抗体的Fab片段，其中前适配体中包含一种通过催化部分子催化反应激活为反应性部分子的前体；(2)将反应性部分子与催化部分子活性位点的氨基酸残基侧链交联，以制备化学程序化抗体。本发明还涵盖了通过这些方法形成的化学程序化抗体、它们的使用方法、制药组合物，以及包括它们的前适配体和共轭物。化学程序化抗体对于治疗癌症，特别是转移性癌症具有用处。