(2-(3-{2-[2-(3-tert-Butoxycarbonylamino-propoxy)-ethoxy]-ethoxy}-propyl)-8-{2-[6-(tert-butoxycarbonyl-methyl-amino)-pyridin-2-yl]-ethoxy}-3-oxo-2,3,4,5-tetrahydro-1H-benzo[c]azepin-4-yl)-acetic acid methyl ester | 801240-05-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯氮卓类
• 英文名称: (2-(3-{2-[2-(3-tert-Butoxycarbonylamino-propoxy)-ethoxy]-ethoxy}-propyl)-8-{2-[6-(tert-butoxycarbonyl-methyl-amino)-pyridin-2-yl]-ethoxy}-3-oxo-2,3,4,5-tetrahydro-1H-benzo[c]azepin-4-yl)-acetic acid methyl ester
• CAS: 801240-05-1
• 化学式: C₄₁H₆₂N₄O₁₁
• 分子量: 786.963
• InChiKey: ZRYFWOQCMRMLDP-UHFFFAOYSA-N

物化性质

• 沸点：
  852.6±65.0 °C(Predicted)
• 密度：
  1.149±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.49
• 重原子数：
  56.0
• 可旋转键数：
  21.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.63
• 拓扑面积：
  164.29
• 氢给体数：
  1.0
• 氢受体数：
  12.0

反应信息

• 作为反应物：
  描述：

  (2-(3-{2-[2-(3-tert-Butoxycarbonylamino-propoxy)-ethoxy]-ethoxy}-propyl)-8-{2-[6-(tert-butoxycarbonyl-methyl-amino)-pyridin-2-yl]-ethoxy}-3-oxo-2,3,4,5-tetrahydro-1H-benzo[c]azepin-4-yl)-acetic acid methyl ester 在 sodium hydroxide 、 苯甲醚 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 水 、 乙腈 为溶剂， 反应 16.0h， 生成 {2-(3-{2-[2-(3-{4-[4-(3,5-Dioxo-hexyl)-phenylcarbamoyl]-butyrylamino}-propoxy)-ethoxy]-ethoxy}-propyl)-8-[2-(6-methylamino-pyridin-2-yl)-ethoxy]-3-oxo-2,3,4,5-tetrahydro-1H-benzo[c]azepin-4-yl}-acetic 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
• 作为产物：
  描述：

  2-溴-5-甲氧基溴苄 在 palladium on activated charcoal 4-二甲氨基吡啶 、 palladium diacetate 、 二乙基异丙基胺 、 偶氮二甲酸二异丙酯 、 四丁基氟化铵 、 氢气 、 三溴化硼 、 溶剂黄146 、 N,N-二异丙基乙胺 、 三苯基膦 、 三(邻甲基苯基)磷 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 xylene 为溶剂， -20.0~90.0 ℃ 、101.33 kPa 条件下， 反应 74.25h， 生成 (2-(3-{2-[2-(3-tert-Butoxycarbonylamino-propoxy)-ethoxy]-ethoxy}-propyl)-8-{2-[6-(tert-butoxycarbonyl-methyl-amino)-pyridin-2-yl]-ethoxy}-3-oxo-2,3,4,5-tetrahydro-1H-benzo[c]azepin-4-yl)-acetic acid methyl ester
  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