(2S)-2-(2-methoxy-2-oxoethyl)-4-[2-[6-[(2-methylpropan-2-yl)oxycarbonylamino]hexanoylamino]ethyl]-3-oxo-2,5-dihydro-1H-1,4-benzodiazepine-7-carboxylic acid | 801239-70-3

• 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: (2S)-2-(2-methoxy-2-oxoethyl)-4-[2-[6-[(2-methylpropan-2-yl)oxycarbonylamino]hexanoylamino]ethyl]-3-oxo-2,5-dihydro-1H-1,4-benzodiazepine-7-carboxylic acid
• CAS: 801239-70-3
• 化学式: C₂₆H₃₈N₄O₈
• 分子量: 534.61
• InChiKey: ZIZQGBYOBDQXBO-FQEVSTJZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  38
• 可旋转键数：
  15
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  163
• 氢给体数：
  4
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  (2S)-2-(2-methoxy-2-oxoethyl)-4-[2-[6-[(2-methylpropan-2-yl)oxycarbonylamino]hexanoylamino]ethyl]-3-oxo-2,5-dihydro-1H-1,4-benzodiazepine-7-carboxylic acid 在 N-甲基吗啉 、 sodium hydroxide 、 1-羟基苯并三唑 、 苯甲醚 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 16.0h， 生成
  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
• 作为产物：
  描述：

  tert-butyl 3-(bromomethyl)-4-fluorobenzoate 在 palladium on activated charcoal iPrN₂Et 、 氢气 、 1-羟基苯并三唑 、 苯甲醚 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 三氟乙酸 作用下， 以 甲醇 、 二氯甲烷 、 二甲基亚砜 、 N,N-二甲基甲酰胺 为溶剂， 反应 77.0h， 生成 (2S)-2-(2-methoxy-2-oxoethyl)-4-[2-[6-[(2-methylpropan-2-yl)oxycarbonylamino]hexanoylamino]ethyl]-3-oxo-2,5-dihydro-1H-1,4-benzodiazepine-7-carboxylic acid
  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

• Antibody targeting compounds
  申请人：THE SCRIPPS RESEARCH INSTITUTE

  公开号：EP2428226A1

  公开（公告）日：2012-03-14

  The present invention provides antibody targeting compounds in which the specificity of the antibody has been reprogrammed by covalently or noncovalently linking a targeting agent to the combining site of an antibody. By this approach, the covalently modified antibody takes on the binding specificity of the targeting agent. The compound may have biological activity provided by the targeting agent or by a separate biological agent. Various uses of the invention compounds are provided.

  本发明提供了抗体靶向化合物，通过共价或非共价方式将靶向制剂与抗体的结合位点连接，对抗体的特异性进行了重新编程。通过这种方法，共价修饰的抗体具有了靶向制剂的结合特异性。化合物的生物活性可由靶向药剂或单独的生物药剂提供。本发明化合物有多种用途。
• ANTIBODY TARGETING COMPOUNDS
  申请人：THE SCRIPPS RESEARCH INSTITUTE

  公开号：EP1443963B1

  公开（公告）日：2014-05-21
• US8252902B2
  申请人：——

  公开号：US8252902B2

  公开（公告）日：2012-08-28
• 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.