carbonic acid p-(bis-2-chloroethylamino)phenol ester-p-nitrophenyl ester | 156078-81-8

• 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: carbonic acid p-(bis-2-chloroethylamino)phenol ester-p-nitrophenyl ester
• 英文别名: 4-(bis(2-chloroethyl)amino)phenyl 4-nitrophenyl carbonate；4-[N,N-bis(2-chloroethyl)amino]phenyl-4-nitrophenyl carbonate；[4-[Bis(2-chloroethyl)amino]phenyl] (4-nitrophenyl) carbonate
• CAS: 156078-81-8
• 化学式: C₁₇H₁₆Cl₂N₂O₅
• 分子量: 399.23
• InChiKey: GDDGMKLRZNWTPR-UHFFFAOYSA-N

物化性质

• 沸点：
  541.8±50.0 °C(Predicted)
• 密度：
  1.402±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  26
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  84.6
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  carbonic acid p-(bis-2-chloroethylamino)phenol ester-p-nitrophenyl ester 在 palladium on activated charcoal 氢气 、 三乙胺 作用下， 以 氯仿 、 乙酸乙酯 为溶剂， 反应 6.0h， 生成 4-[N,N-bis(2-chloroethyl)amino]-phenoxycarbonyl-L-glutamic acid
  参考文献：
  名称：

  用于抗体指导的酶前药治疗的新型芥末前药：酰胺连接的替代物。

  摘要：

  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，

  DOI：

  10.1021/jm950671l
• 作为产物：
  描述：

  4--O-benzylphenol 在 palladium on activated charcoal 盐酸 、 氢气 、 甲基磺酰氯 、 三乙胺 作用下， 以 吡啶 、 甲醇 、 乙醇 、 甲苯 为溶剂， 反应 1.0h， 生成 carbonic acid p-(bis-2-chloroethylamino)phenol ester-p-nitrophenyl ester
  参考文献：
  名称：

  Melanocyte-directed enzyme prodrug therapy (MDEPT): development of a targeted treatment for malignant melanoma

  摘要：

  A novel prodrug rationally designed to function as a tyrosinase substrate has been synthesised to allow targeted treatment of malignant melanoma. This agent has been evaluated for tyrosinase-mediated drug release, and has been shown to act in the desired manner. Furthermore, differential cytotoxicity has been demonstrated in cell lines which express tyrosinase and those which do not.

  DOI：

  10.1016/s0968-0896(99)00126-1

文献信息

• 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。
• Phenylethylamine derivatives and their use in the treatment of melanoma
  申请人：——

  公开号：US20040029967A1

  公开（公告）日：2004-02-12

  Novel mono- and dihydroxy phenylethylamine derivatives useful in treating melanoma are provided having the formulae (Ia, Ib or Ic). In the above formulae, R a is hydrogen or —COOR b, R b is hydrogen or C 1-6 alkyl; R e and R e independently represent hydrogen and hydroxy, R f is hydrogen, C 1-4? alkyl or halogen, X is —CHOH—, —CH 2 -oxygen or sulphur, m is zero or 1, W is oxygen or sulphur, and —ODrug, —NHDrug and —N(Drug) 2 each represent a residue of a therapeutically active agent. The above compounds are prodrugs which are inactive until metabolised by enzymes expressed by host melanoma cells. The invention allows a greater amount of active agent to be used while reducing systemic side effects. 1

  提供了用于治疗黑色素瘤的新型单氢和二羟基苯乙胺衍生物，其化学式为（Ia、Ib或Ic）。在上述化学式中，R是氢或—COORb，Rb是氢或C1-6烷基；Re和Re独立表示氢和羟基，Rf是氢、C1-4烷基或卤素，X是—CHOH—、—CH2-氧或硫，m为零或1，W是氧或硫，而—ODrug、—NHDrug和—N（Drug）2分别表示治疗活性剂的残基。上述化合物是一种前药，在被宿主黑色素瘤细胞表达的酶代谢之前是无效的。该发明允许使用更多的活性剂而减少全身副作用。
• [EN] PHENYLETHYLAMINE DERIVATIVES AND THEIR USE IN THE TREATMENT OF MELANOMA<br/>[FR] DERIVES DE PHENYLETHYLAMINE ET LEUR UTILISATION DANS LE TRAITEMENT DE MELANOME
  申请人：RILEY PATRICK ANTHONY

  公开号：WO2002008174A1

  公开（公告）日：2002-01-31

  Novel mono- and dihydroxy phenylethylamine derivatives useful in treating melanoma are provided having the formulae (Ia, Ib or Ic). In the above formulae, Ra is hydrogen or -COORb, Rb is hydrogen or C¿1-6? alkyl; R?e and Re¿ independently represent hydrogen and hydroxy, Rf is hydrogen, C¿1-4? alkyl or halogen, X is -CHOH-, -CH2-oxygen or sulphur, m is zero or 1, W is oxygen or sulphur, and -ODrug, -NHDrug and -N(Drug)2 each represent a residue of a therapeutically active agent. The above compounds are prodrugs which are inactive until metabolised by enzymes expressed by host melanoma cells. The invention allows a greater amount of active agent to be used while reducing systemic side effects.

  本发明提供了一种在治疗黑色素瘤方面有用的新型单和双羟基苯乙胺衍生物，其化学式为（Ia，Ib或Ic）。在上述化学式中，Ra为氢或-COORb，Rb为氢或C1-6烷基；Re和Re'独立地表示氢和羟基，Rf为氢，C1-4烷基或卤素，X为-CHOH-，-CH2-氧或硫，m为零或1，W为氧或硫，-ODrug，-NHDrug和-N（Drug）2分别表示治疗活性剂的残基。上述化合物是前药，在被宿主黑色素瘤细胞表达的酶代谢之前是不活性的。本发明允许使用更多的活性剂而减少全身副作用。
• 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。
• Novel DNA-directed alkylating agents: Design, synthesis and potent antitumor effect of phenyl N-mustard-9-anilinoacridine conjugates via a carbamate or carbonate linker
  作者：Naval Kapuriya、Kalpana Kapuriya、Huajin Dong、Xiuguo Zhang、Ting-Chao Chou、Yu-Ting Chen、Te-Chang Lee、Wen-Chuan Lee、Tung-Hu Tsai、Yogesh Naliapara、Tsann-Long Su

  DOI：10.1016/j.bmc.2008.12.022

  日期：2009.2

  A series of phenyl N-mustard-9-anilinoacridine conjugates via a carbamate or carbonate linker was synthesized for antitumor evaluation. The carbamate or carbonate linker is able to lower the reactivity of the phenyl N-mustard pharmacophore and thus, these conjugates are rather chemically stable. The in vitro studies revealed that these derivatives possessed significant cytotoxicity with IC50 in sub-micromolar range in inhibiting human lymphoblastic leukemia (CCRF-CEM), breast carcinoma (MX-1), colon carcinoma (HCT-116) and human non-small cell lung cancer (H1299) cell growth in vitro. Compounds 10a, 10b, 10e, 10i, and 15a were selected for evaluating their antitumor activity in nude mice bearing MX1 and HCT-116 xenografts. Remarkably, total tumor remission was achieved by these agents with only one cycle of treatment. Interestingly, no tumor relapse was found in mice treated with 10a over 129 days. This agent is capable of inducing DNA interstrand cross-linking in human non-small lung cancer H1299 cells in a dose dependent manner by modified comet assay and has a long half-life in rat plasma. (c) 2008 Elsevier Ltd. All rights reserved.