4-[N,N-bis(2-chloroethyl)amino]phenyl chloroformate | 52177-49-8

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: 4-[N,N-bis(2-chloroethyl)amino]phenyl chloroformate
• 英文别名: p-phenyl-chloroformat；p-(Bis-2-chlorethylamino)phenyl-chloroformat；4-[Bis(2-chloroethyl)amino]phenyl chloroformate；[4-[bis(2-chloroethyl)amino]phenyl] carbonochloridate
• CAS: 52177-49-8
• 化学式: C₁₁H₁₂Cl₃NO₂
• 分子量: 296.581
• InChiKey: GNSBYIAIRMLLQS-UHFFFAOYSA-N

物化性质

• 沸点：
  386.8±37.0 °C(Predicted)
• 密度：
  1.374±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  17
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  29.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-[N,N-bis(2-chloroethyl)amino]phenyl chloroformate 在 sodium hydroxide 、 sodium methylate 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 甲醇 、 丙酮 为溶剂， 生成 (2S,3S,4S,5R,6S)-6-[2-[[4-[bis(2-chloroethyl)amino]phenoxy]carbonyl-methylamino]-4-nitrophenoxy]-3,4,5-trihydroxyoxane-2-carboxylic acid
  参考文献：
  名称：

  Glucuronide prodrugs of hydroxy compounds for antibody directed enzyme prodrug therapy (ADEPT) : A phenol nitrogen mustard carbamate

  摘要：

  A prodrug consisting of a beta-D-glucuronic acid linked to a self-immolative spacer (a N-(orthohydroxyphenyl)-N-methylcarbamate) and a phenolic nitrogen mustard was synthesised. As this prodrug was easily cleaved by a beta-glucuronidase enzyme and displayed low cytotoxicity, it must be considered as appropriate for an ADEPT approach. (C) 1997 Elsevier Science Ltd.

  DOI：

  10.1016/s0960-894x(97)00157-1
• 作为产物：
  描述：

  4-[双(2-羟乙基)氨基]苯酚 在 palladium on activated charcoal 氢氧化钾 、 氢气 、 甲基磺酰氯 、 三乙胺 作用下， 以 吡啶 、 乙醇 为溶剂， 生成 4-[N,N-bis(2-chloroethyl)amino]phenyl chloroformate
  参考文献：
  名称：

  Glucuronide prodrugs of hydroxy compounds for antibody directed enzyme prodrug therapy (ADEPT) : A phenol nitrogen mustard carbamate

  摘要：

  A prodrug consisting of a beta-D-glucuronic acid linked to a self-immolative spacer (a N-(orthohydroxyphenyl)-N-methylcarbamate) and a phenolic nitrogen mustard was synthesised. As this prodrug was easily cleaved by a beta-glucuronidase enzyme and displayed low cytotoxicity, it must be considered as appropriate for an ADEPT approach. (C) 1997 Elsevier Science Ltd.

  DOI：

  10.1016/s0960-894x(97)00157-1

文献信息

• New Mustard Prodrugs for Antibody-Directed Enzyme Prodrug Therapy:  Alternatives to the Amide Link
  作者：Robert I. Dowell、Caroline J. Springer、David H. Davies、Elizabeth M. Hadley、Philip J. Burke、F. Thomas Boyle、Roger G. Melton、Thomas A. Connors、David C. Blakey、Anthony B. Mauger

  DOI：10.1021/jm950671l

  日期：1996.1.1

  Antibody-directed enzyme prodrug therapy (ADEPT) is a two-step approach for the treatment of cancer which seeks to generate a potent cytotoxic agent selectively at a tumor site. In this work described the cytotoxic agent is generated by the action of an enzyme CPG2 on a relatively nontoxic prodrug. The prodrug 1 currently on clinical trial is a benzamide and is cleaved by CPG2 to a benzoic acid mustard

  抗体导向酶前药疗法（ADEPT）是一种用于癌症治疗的两步法，旨在在肿瘤部位选择性地产生有效的细胞毒剂。在这项工作中，描述了细胞毒性剂是通过酶CPG2对相对无毒的前药产生的。当前正在临床试验中的前药1是苯甲酰胺，并被CPG2裂解为苯甲酸芥子气药物1a。我们合成了一系列新的前药3-8，其中的苯甲酰胺键已被例如氨基甲酸酯或脲基取代。这些替代链接中的一些已被证明是CPG2的良好底物，因此是ADEPT的新候选者。源自这些前药中最好的一种的活性药物3a和4a是有效的细胞毒剂（1-2 microM），大约是1a的100倍。前药3和4的细胞毒性降低了约100-200倍，
• Prodrugs for the therapy of tumors and inflammatory disorders
  申请人：Heochst Aktiengesellschaft

  公开号：US05935995A1

  公开（公告）日：1999-08-10

  Compounds of the formula I glycosyl-Y\x9b--C(.dbd.Y)--X--!.sub.p --W(R).sub.n --Z--C(.dbd.Y)-active compound (I) are described which are suitable for the treatment of carcinomatous diseases, autoimmune diseases and chronic inflammatory diseases such as rheumatoid arthritis.

  化合物的公式I糖基-Y\x9b--C(.dbd.Y)--X--!.sub.p --W(R).sub.n --Z--C(.dbd.Y)-活性化合物（I）适用于治疗癌症性疾病、自身免疫疾病和慢性炎症性疾病，如类风湿性关节炎。
• Aniline or phenol mustards linked to DNA-affinic molecules or water-soluble aromatic rings and their use as cancer therapeutic agents
  申请人：Su Tsann-Long

  公开号：US20080171765A1

  公开（公告）日：2008-07-17

  New aniline or phenol N-mustards linked to DNA-affinity carriers (such as 9-anilinoacridines, acridines and quinolines), aminobenzamides or aminophenol ethers by a urea, carbamic acid, carbanic acid ester, hydrazineurea, hydrazinecarbamic acid ester, phenoxyurea, phenoxycarbamic acid ester linkage with improved chemical stability and anti-tumor therapeutic efficacy are provided.

  提供了与DNA亲和载体（如9-苯胺基吖啶、吖啶和喹啉）、氨基苯甲酰胺或氨基酚醚通过脲、碳酸酯、碳酸酯、叠氮脲、叠氮碳酸酯、苯氧基脲、苯氧基碳酸酯链接的新苯胺或酚N-芥子素，具有改善的化学稳定性和抗肿瘤治疗效果。
• PHENYL N-MUSTARD LINKED TO DNA-AFFINIC MOLECULES OR WATER-SOLUBLE ARYL RINGS, METHOD AND THEIR USE AS CANCER THERAPEUTIC AGENTS
  申请人：SU Tsann-Long

  公开号：US20130178494A1

  公开（公告）日：2013-07-11

  The present disclosure relates to new DNA-directed alkylating agents and water-soluble N-mustard agents with improved chemical stability and anti-tumor therapeutic efficacy.

  本公开涉及新的DNA定向烷基化剂和具有改善化学稳定性和抗肿瘤治疗效果的水溶性N-芥子剂。
• Edwards,P.D. et al., Journal of the Chemical Society. Perkin transactions I, 1973, p. 2397 - 2402
  作者：Edwards,P.D. et al.

  DOI：——

  日期：——