4-bis(2'-mesyloxyethyl)amino-N-tert-butyloxycarbonylaniline | 528836-52-4

• 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: 4-bis(2'-mesyloxyethyl)amino-N-tert-butyloxycarbonylaniline
• 英文别名: ((4-((tert-butoxycarbonyl)amino)phenyl)azanediyl)bis(ethane-2,1-diyl) dimethanesulfonate
• CAS: 528836-52-4
• 化学式: C₁₇H₂₈N₂O₈S₂
• 分子量: 452.55
• InChiKey: JBKHOOWATQFPOY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.79
• 重原子数：
  29.0
• 可旋转键数：
  10.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.59
• 拓扑面积：
  128.31
• 氢给体数：
  1.0
• 氢受体数：
  9.0

反应信息

• 作为反应物：
  描述：

  4-bis(2'-mesyloxyethyl)amino-N-tert-butyloxycarbonylaniline 在 lithium bromide 作用下， 以 四氢呋喃 为溶剂， 以73.5%的产率得到4-bis(2'-bromoethyl)amino-N-tert-butyloxycarbonylaniline
  参考文献：
  名称：

  Self-Immolative Nitrogen Mustards Prodrugs Cleavable by Carboxypeptidase G2 (CPG2) Showing Large Cytotoxicity Differentials in GDEPT

  摘要：

  Nineteen novel potential self-immolative prodrugs and their corresponding drugs have been synthesized for gene-directed enzyme prodrug therapy (GDEPT) with carboxypeptidase G2 (CPG2) as the activating enzyme. The compounds are derived from o- and p-amino and p-methylamino aniline nitrogen mustards. Their aqueous stability, kinetics of drug release by CPG2, and cytotoxicity in the colon carcinoma cell line WiDr, expressing either surface-tethered CPG2 (stCPG2(Q)3) or control beta-galactosidase, are assessed. The effect of various structural features on stability, kinetics of activation, and biological activity is discussed. The p-methylamino prodrugs are the most stable compounds from this series, with the largest cytotoxicity differentials between CPG2-expressing and nonexpressing cells. The most potent compounds in all series are prodrugs of bis-iodo nitrogen mustards. 4-{N-[4'-Bis(2"-iodoethyl)aminophenyll-N'-methylcarbamoyloxymethyl}phenylcarbamoyl-L-glutamic acid, compound 39b, is 124-fold more cytotoxic to WiDr cells expressing CPG2 than to cells expressing beta-galactosidase. An additional six compounds show better cytotoxicity differential than the published N-{4-[(2-chloroethyl)(2-mesyloxyethyl)amino]benzoyl}-L-glutamic acid (CMDA) prodrug.

  DOI：

  10.1021/jm020462i
• 作为产物：
  描述：

  N,N-bis(2-{[tert-butyldimethylsilyl]oxy}ethyl)-4-nitroaniline 在 palladium on activated charcoal 4-二甲氨基吡啶 、 triethylamine trihydrofluoride 、 氢气 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 22.0h， 生成 4-bis(2'-mesyloxyethyl)amino-N-tert-butyloxycarbonylaniline
  参考文献：
  名称：

  Self-Immolative Nitrogen Mustards Prodrugs Cleavable by Carboxypeptidase G2 (CPG2) Showing Large Cytotoxicity Differentials in GDEPT

  摘要：

  Nineteen novel potential self-immolative prodrugs and their corresponding drugs have been synthesized for gene-directed enzyme prodrug therapy (GDEPT) with carboxypeptidase G2 (CPG2) as the activating enzyme. The compounds are derived from o- and p-amino and p-methylamino aniline nitrogen mustards. Their aqueous stability, kinetics of drug release by CPG2, and cytotoxicity in the colon carcinoma cell line WiDr, expressing either surface-tethered CPG2 (stCPG2(Q)3) or control beta-galactosidase, are assessed. The effect of various structural features on stability, kinetics of activation, and biological activity is discussed. The p-methylamino prodrugs are the most stable compounds from this series, with the largest cytotoxicity differentials between CPG2-expressing and nonexpressing cells. The most potent compounds in all series are prodrugs of bis-iodo nitrogen mustards. 4-{N-[4'-Bis(2"-iodoethyl)aminophenyll-N'-methylcarbamoyloxymethyl}phenylcarbamoyl-L-glutamic acid, compound 39b, is 124-fold more cytotoxic to WiDr cells expressing CPG2 than to cells expressing beta-galactosidase. An additional six compounds show better cytotoxicity differential than the published N-{4-[(2-chloroethyl)(2-mesyloxyethyl)amino]benzoyl}-L-glutamic acid (CMDA) prodrug.

  DOI：

  10.1021/jm020462i

文献信息

• Introducing a squaramide-based self-immolative spacer for controlled drug release
  作者：Marta Ximenis、Angel Sampedro、Luis Martínez-Crespo、Guillem Ramis、Francisca Orvay、Antonio Costa、Carmen Rotger

  DOI：10.1039/d0cc07683j

  日期：——

  Herein we report the design, synthesis and assessment of the first example of a squaramide-based self-immolative system triggered by an enzymatic reduction. We have proved that the release of the alkylating agent N′,N′-(bis(2-chloroethyl)benzene)-1,4-diamine (ANM) provokes a dramatic reduction of the survival factor in glioblastoma cells, evidencing the suitability of the squaramide-based spacer for drug

  本文中，我们报告了由酶促还原反应引发的基于方胺的自燃系统的第一个实例的设计，合成和评估。我们已经证明，烷基化剂N ′，N ′ -（双（2-氯乙基）苯）-1,4-二胺（ANM）的释放引起胶质母细胞瘤细胞中生存因子的显着降低，证明了其适用性。基于方胺的间隔基，用于药物输送应用。