4-bis(2'-tert-butyldimethylsilyloxyethyl)amino-N-tert-butyloxycarbonylaniline | 244247-70-9

• 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'-tert-butyldimethylsilyloxyethyl)amino-N-tert-butyloxycarbonylaniline
• 英文别名: 4-[bis(2-tert-butyldimethylsilyloxyethyl)amino]-N-(tert-butoxycarbonyl)aniline；tert-butyl N-[4-[bis[2-[tert-butyl(dimethyl)silyl]oxyethyl]amino]phenyl]carbamate
• CAS: 244247-70-9
• 化学式: C₂₇H₅₂N₂O₄Si₂
• 分子量: 524.892
• InChiKey: GOPHAURXVMDFQL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.88
• 重原子数：
  35
• 可旋转键数：
  14
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.74
• 拓扑面积：
  60
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-bis(2'-tert-butyldimethylsilyloxyethyl)amino-N-tert-butyloxycarbonylaniline 在 4-二甲氨基吡啶 、 triethylamine trihydrofluoride 、 三乙胺 、 lithium bromide 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 生成 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-(4-硝基苯基)二乙醇胺 在 palladium on activated charcoal 咪唑 、 氢气 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 42.0h， 生成 4-bis(2'-tert-butyldimethylsilyloxyethyl)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

• Anti-tumor agents
  申请人：Astrazeneca AB

  公开号：US06472435B1

  公开（公告）日：2002-10-29

  The invention concerns anti-tumor agents of formula (I), wherein each of R1, R2 and R3 has the meanings defined in the specification including hydrogen, (1-4C)alkyl, (3-4C)alkynyl and (1-4C)alkoxyl; each of R4 and R5 is (1-4C) alkyl; each of R6 and R7 is hydrogen or (1-4C)alkyl; X is N-(1-4C)alkylimino, N-(3-4C)alkenylimino, or (3-4C)alkynylimino; m is 1 or 2 and each R8 is as defined in the specification; each Y′ and Y2 is halogen, (1-4C)alkanesulphonyloxy, benzensulphonyloxy or phenyl-(1-4C)alkanesulfonyloxy; or a pharmaceutical acceptable salt thereof; provided that at least one of R1, R2 and R3 is other than hydrogen; a process for their preparation, pharmaceutical composition containing them and their use for producing an anti-proliferative effect in a warm-blooded animal.

  本发明涉及式（I）的抗肿瘤剂，其中R1，R2和R3中的每一个具有规范中定义的含义，包括氢，（1-4C）烷基，（3-4C）炔基和（1-4C）烷氧基; R4和R5中的每一个是（1-4C）烷基; R6和R7中的每一个是氢或（1-4C）烷基; X是N-(1-4C)烷基亚胺基，N-(3-4C)烯基亚胺基或（3-4C）炔基亚胺基; m为1或2，每个R8如规范中所定义; 每个Y′和Y2是卤素，（1-4C）烷磺酰氧基，苯基磺酰氧基或苯基-(1-4C)烷基磺酰氧基; 或其药物可接受的盐; 前提是至少有一个R1，R2和R3不是氢; 它们的制备方法，含有它们的药物组合物以及它们用于在温血动物中产生抗增殖作用的用途。
• Self-Immolative Nitrogen Mustards Prodrugs Cleavable by Carboxypeptidase G2 (CPG2) Showing Large Cytotoxicity Differentials in GDEPT
  作者：Dan Niculescu-Duvaz、Ion Niculescu-Duvaz、Frank Friedlos、Jan Martin、Panos Lehouritis、Richard Marais、Caroline J. Springer

  DOI：10.1021/jm020462i

  日期：2003.4.1

  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.