2-(3-(tert-butyldiphenylsilyloxy)propyl)oxazolidine | 873923-25-2

• 分子结构分类: 有机化合物 - 有机金属化合物 - 有机类金属化合物
• 英文名称: 2-(3-(tert-butyldiphenylsilyloxy)propyl)oxazolidine
• 英文别名: 2-(3-{[tert-Butyl(diphenyl)silyl]oxy}propyl)-1,3-oxazolidine；tert-butyl-[3-(1,3-oxazolidin-2-yl)propoxy]-diphenylsilane
• CAS: 873923-25-2
• 化学式: C₂₂H₃₁NO₂Si
• 分子量: 369.579
• InChiKey: GKVNVAPUEKJGHY-UHFFFAOYSA-N

物化性质

• 沸点：
  436.5±41.0 °C(Predicted)
• 密度：
  1.05±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.29
• 重原子数：
  26
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  30.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-(3-(tert-butyldiphenylsilyloxy)propyl)oxazolidine 在 哌啶 、 吡啶 、 四丁基氟化铵 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 生成 2-(3-Oxo-propyl)-oxazolidine-3-carboxylic acid 4-((S)-2-{(S)-2-[6-(2,5-dioxo-2,5-dihydro-pyrrol-1-yl)-hexanoylamino]-3-methyl-butyrylamino}-propionylamino)-benzyl ester
  参考文献：
  名称：

  Dipeptide-based highly potent doxorubicin antibody conjugates

  摘要：

  Highly potent and novel derivatives of doxorubicin were linked to monoclonal antibodies (mAbs) for site-specific drug delivery. Drug linker 5 consisted of a dipeptide linker attached directly to the daunosamine nitrogen of the n-butyldiacetate doxorubicin derivative 2a. Upon hydrolysis of the peptide linker and acetate groups, the free daunosamine nitrogen is able to form the highly potent 2-pyrrolinodoxorubicin (3a). The second approach involved the use of an oxazolidine carbamate (13) to mask an activating aldehyde group until proteolytic hydrolysis releases 3a. Both drug linkers were shown to be substrates for the lysosomal enzyme cathepsin B. Each molecule was conjugated to the mAbs c1F6 (anti-CD70) and cAC10 (anti-CD30) to give potent drug conjugates against renal cell carcinoma and anaplastic large cell lymphoma cell lines, respectively. The activities were immunologically selective, since antigen negative cell lines were much less sensitive to treatment with the drug conjugates. The approaches described here for attaching highly potent doxorubicin derivatives to mAbs are novel and allow for control of drug stability while covalently bound to the delivery agent. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.09.081
• 作为产物：
  描述：

  4-(tret-butyldiphenylsilyloxy)butan-1-ol 以 二氯甲烷 、 苯 为溶剂， 生成 2-(3-(tert-butyldiphenylsilyloxy)propyl)oxazolidine
  参考文献：
  名称：

  Dipeptide-based highly potent doxorubicin antibody conjugates

  摘要：

  Highly potent and novel derivatives of doxorubicin were linked to monoclonal antibodies (mAbs) for site-specific drug delivery. Drug linker 5 consisted of a dipeptide linker attached directly to the daunosamine nitrogen of the n-butyldiacetate doxorubicin derivative 2a. Upon hydrolysis of the peptide linker and acetate groups, the free daunosamine nitrogen is able to form the highly potent 2-pyrrolinodoxorubicin (3a). The second approach involved the use of an oxazolidine carbamate (13) to mask an activating aldehyde group until proteolytic hydrolysis releases 3a. Both drug linkers were shown to be substrates for the lysosomal enzyme cathepsin B. Each molecule was conjugated to the mAbs c1F6 (anti-CD70) and cAC10 (anti-CD30) to give potent drug conjugates against renal cell carcinoma and anaplastic large cell lymphoma cell lines, respectively. The activities were immunologically selective, since antigen negative cell lines were much less sensitive to treatment with the drug conjugates. The approaches described here for attaching highly potent doxorubicin derivatives to mAbs are novel and allow for control of drug stability while covalently bound to the delivery agent. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.09.081

文献信息

• [EN] PROCESS FOR THE PREPARATION OF GLUCURONIDE DRUG-LINKERS AND INTERMEDIATES THEREOF<br/>[FR] PROCÉDÉ DE PRÉPARATION DE LIEURS DE MÉDICAMENT, À BASE DE GLUCURONIDE, ET LEURS INTERMÉDIAIRES
  申请人：SEATTLE GENETICS INC

  公开号：WO2018175994A1

  公开（公告）日：2018-09-27

  The present invention provides improved processes for the preparation of drug-linkers with a β-glucuronide cleavable unit, as well as intermediates thereof.

  本发明提供了一种改进的制备具有β-葡聚糖醇可切割单元的药物连接剂的工艺，以及其中间体。
• Beta-Glucuronide-Linker Drug Conjugates
  申请人：Jeffrey Scott

  公开号：US20080241128A1

  公开（公告）日：2008-10-02

  Ligand Drug conjugate compounds comprising a β-glucuronide-based linker and methods of using such compounds are provided.

  提供了包含基于β-葡萄糖醛酸的连接剂的配体药物共轭化合物及使用这种化合物的方法。
• β-glucuronide-linker drug conjugates
  申请人：Seattle Genetics, Inc.

  公开号：US08039273B2

  公开（公告）日：2011-10-18

  Ligand Drug conjugate compounds comprising a β-glucuronide-based linker and methods of using such compounds are provided.

  提供了包括β-葡萄糖醛酸基连接物的配体药物结合物化合物以及使用这些化合物的方法。
• BETA-GLUCURONIDE-LINKER DRUG CONJUGATES
  申请人：Jeffrey Scott

  公开号：US20140031535A1

  公开（公告）日：2014-01-30

  Ligand Drug conjugate compounds comprising a β-glucuronide-based linker and methods of using such compounds are provided.

  本发明提供了包括基于β-葡萄糖醛酸的连接物的配体药物结合物化合物以及使用这种化合物的方法。
• Beta-glucuronide-linker drug conjugates
  申请人：Jeffrey Scott

  公开号：US08568728B2

  公开（公告）日：2013-10-29

  Ligand Drug conjugate compounds comprising a β-glucuronide-based linker and methods of using such compounds are provided.

  提供了一种包括β-葡萄糖醛酸酯为连接物的配体药物结合物化合物以及使用这种化合物的方法。