diallyl 4-{[4'-bis(2''-tert-butyldimethylsilyloxyethyl)aminophenyl]carbamoyloxymethyl}phenylcarbamoyl-L-glutamate | 528836-39-7

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: diallyl 4-{[4'-bis(2''-tert-butyldimethylsilyloxyethyl)aminophenyl]carbamoyloxymethyl}phenylcarbamoyl-L-glutamate
• 英文别名: bis(prop-2-enyl) (2S)-2-[[4-[[4-[bis[2-[tert-butyl(dimethyl)silyl]oxyethyl]amino]phenyl]carbamoyloxymethyl]phenyl]carbamoylamino]pentanedioate
• CAS: 528836-39-7
• 化学式: C₄₂H₆₆N₄O₉Si₂
• 分子量: 827.178
• InChiKey: QYBQJBOFVMQOCB-BHVANESWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  9.01
• 重原子数：
  57
• 可旋转键数：
  27
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  154
• 氢给体数：
  3
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  diallyl 4-{[4'-bis(2''-tert-butyldimethylsilyloxyethyl)aminophenyl]carbamoyloxymethyl}phenylcarbamoyl-L-glutamate 在 四氢吡咯 、 4-二甲氨基吡啶 、 四(三苯基膦)钯 、 triethylamine trihydrofluoride 、 三乙胺 、 lithium bromide 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 10.0h， 生成 (S)-2-[3-(4-{4-[Bis-(2-bromo-ethyl)-amino]-phenylcarbamoyloxymethyl}-phenyl)-ureido]-pentanedioic acid
  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-(4-硝基苯基)二乙醇胺 在 palladium on activated charcoal 咪唑 、 dibutyltin(II) dilaurate 、 氢气 、 三乙胺 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 46.25h， 生成 diallyl 4-{[4'-bis(2''-tert-butyldimethylsilyloxyethyl)aminophenyl]carbamoyloxymethyl}phenylcarbamoyl-L-glutamate
  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