[(2S)-2-[[tert-butyl(dimethyl)silyl]oxymethyl]pyrrolidin-1-yl]-(2-isocyanato-4,5-dimethoxyphenyl)methanone | 848004-21-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: [(2S)-2-[[tert-butyl(dimethyl)silyl]oxymethyl]pyrrolidin-1-yl]-(2-isocyanato-4,5-dimethoxyphenyl)methanone
• CAS: 848004-21-7
• 化学式: C₂₁H₃₂N₂O₅Si
• 分子量: 420.581
• InChiKey: SJYGXCNGIBLDJC-HNNXBMFYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  29
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  77.4
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  [(2S)-2-[[tert-butyl(dimethyl)silyl]oxymethyl]pyrrolidin-1-yl]-(2-isocyanato-4,5-dimethoxyphenyl)methanone 在 四氢吡咯 、 重铬酸吡啶 、 四(三苯基膦)钯 、 4 A molecular sieve 、 TEA 、 溶剂黄146 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 23.0h， 生成 (2S)-2-[[4-[[(6S,6aS)-6-hydroxy-2,3-dimethoxy-11-oxo-6a,7,8,9-tetrahydro-6H-pyrrolo[2,1-c][1,4]benzodiazepine-5-carbonyl]oxymethyl]phenoxy]carbonylamino]pentanedioic acid
  参考文献：
  名称：

  Synthesis and biological evaluation of novel pyrrolo[2,1-c][1,4]benzodiazepine prodrugs for use in antibody-directed enzyme prodrug therapy

  摘要：

  The design, synthesis and evaluation of four novel pyrrolo[2,1-c][1,4]benzodiazepine (PBD) prodrugs (1a,b and 2a,b; Fig. 1) for potential use in carboxypeptidase G2 (CPG2)-based anti body-directed enzyme prodrug therapy (ADEPT) is reported. Although all four prodrugs were shown to be less cytotoxic than the released parent PBDs 3 and 4, the urea prodrugs 1b and 2b were found to be too unstable for use in ADEPT, whereas carbamates 1a and 2a are both stable in an aqueous environment and are good substrates for CPG2. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.10.017
• 作为产物：
  描述：

  (2-amino-4,5-dimethoxyphenyl)-[(2S)-2-[[tert-butyl(dimethyl)silyl]oxymethyl]pyrrolidin-1-yl]methanone 、 三光气 在 三乙胺 作用下， 以 甲苯 为溶剂， 反应 2.0h， 生成 [(2S)-2-[[tert-butyl(dimethyl)silyl]oxymethyl]pyrrolidin-1-yl]-(2-isocyanato-4,5-dimethoxyphenyl)methanone
  参考文献：
  名称：

  [EN] SYNTHESIS OF PROTECTED PYRROLOBENZODIAZEPINES
  [FR] SYNTHESE DE PYRROLOBENZODIAZEPINES PROTEGEES

  摘要：

  通过公式（II）或公式（V）的中间体合成公式（I）的N-10保护的PBD化合物的方法。

  公开号：

  WO2005023814A1

文献信息

• [EN] SYNTHESIS OF PROTECTED PYRROLOBENZODIAZEPINES<br/>[FR] SYNTHESE DE PYRROLOBENZODIAZEPINES PROTEGEES
  申请人：SPIROGEN LTD

  公开号：WO2005023814A1

  公开（公告）日：2005-03-17

  A method of synthesis of a N-10 protected PBD compound of formula (I) via an intermediate of formula (II) or formula (V).

  通过公式（II）或公式（V）的中间体合成公式（I）的N-10保护的PBD化合物的方法。
• Synthesis and biological evaluation of novel pyrrolo[2,1-c][1,4]benzodiazepine prodrugs for use in antibody-directed enzyme prodrug therapy
  作者：Luke A. Masterson、Victoria J. Spanswick、John A. Hartley、Richard H. Begent、Philip W. Howard、David E. Thurston

  DOI：10.1016/j.bmcl.2005.10.017

  日期：2006.1

  The design, synthesis and evaluation of four novel pyrrolo[2,1-c][1,4]benzodiazepine (PBD) prodrugs (1a,b and 2a,b; Fig. 1) for potential use in carboxypeptidase G2 (CPG2)-based anti body-directed enzyme prodrug therapy (ADEPT) is reported. Although all four prodrugs were shown to be less cytotoxic than the released parent PBDs 3 and 4, the urea prodrugs 1b and 2b were found to be too unstable for use in ADEPT, whereas carbamates 1a and 2a are both stable in an aqueous environment and are good substrates for CPG2. (c) 2005 Elsevier Ltd. All rights reserved.