4-(N,N-bis-chloroethylamino-phenyl)butyl(N-hydroxysuccinimide)ester | 56842-79-6

• 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-chloroethylamino-phenyl)butyl(N-hydroxysuccinimide)ester
• 英文别名: N-hydroxysuccinimidyl chlorambucil ester；chlorambucil N-hydroxysuccinimidyl ester；chlorambucil NHS ester；2,5-Pyrrolidinedione, 1-(4-(4-(bis(2-chloroethyl)amino)phenyl)-1-oxobutoxy)-；(2,5-dioxopyrrolidin-1-yl) 4-[4-[bis(2-chloroethyl)amino]phenyl]butanoate
• CAS: 56842-79-6
• 化学式: C₁₈H₂₂Cl₂N₂O₄
• 分子量: 401.29
• InChiKey: XORXHHUFMDZCAS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  26
• 可旋转键数：
  11
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  66.9
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-(N,N-bis-chloroethylamino-phenyl)butyl(N-hydroxysuccinimide)ester 、 L-组氨酸 在 sodium hydroxide 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以77.4%的产率得到(S)-2-(4-(4-(bis(2-chloroethyl)amino)phenyl)butanamido)-3-(1H-imidazol-4-yl)propanoic acid
  参考文献：
  名称：

  Synthesis and biological evaluation of 99mTc(CO)3(His–CB) as a tumor imaging agent

  摘要：

  The chlorambucil L-histidine conjugate was synthesized and radiolabeled with [Tc-99m(CO)(3)](+) core to form the Tc-99m(CO)(3)(His-CB) complex. The radiochemical purity of the complex was over 90%. It had good hydrophilicity and was stable at room temperature. The high initial tumor uptake with certain retention, fast clearance from background, good tumor/non-tumor ratios and satisfactory scintigraphic images highlighted the potential of Tc-99m(CO)(3)(His-CB) as a tumor imaging agent. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.10.062
• 作为产物：
  描述：

  N-羟基丁二酰亚胺 、 苯丁酸氮芥 在 N,N'-二环己基碳二亚胺 作用下， 以 乙腈 为溶剂， 以86.6%的产率得到4-(N,N-bis-chloroethylamino-phenyl)butyl(N-hydroxysuccinimide)ester
  参考文献：
  名称：

  Synthesis and biological evaluation of 99mTc(CO)3(His–CB) as a tumor imaging agent

  摘要：

  The chlorambucil L-histidine conjugate was synthesized and radiolabeled with [Tc-99m(CO)(3)](+) core to form the Tc-99m(CO)(3)(His-CB) complex. The radiochemical purity of the complex was over 90%. It had good hydrophilicity and was stable at room temperature. The high initial tumor uptake with certain retention, fast clearance from background, good tumor/non-tumor ratios and satisfactory scintigraphic images highlighted the potential of Tc-99m(CO)(3)(His-CB) as a tumor imaging agent. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.10.062

文献信息

• Methods and compositions for treating cancer
  申请人：Eissigmann M. John

  公开号：US20060019936A1

  公开（公告）日：2006-01-26

  The invention provides compounds and methods for treating cancer. Exemplary compounds are multi-functional compounds with two different moieties connected by a linker. Compounds of the invention can activate one or more pathways that result in the inhibition of cell growth. The invention includes cytostatic and cytotoxic compounds. Methods and compositions of the invention are particularly useful for treating cancer cells that are resistant to other chemotherapeutic drugs.

  这项发明提供了用于治疗癌症的化合物和方法。示例化合物是具有两种不同基团通过连接剂连接的多功能化合物。该发明的化合物可以激活导致细胞生长抑制的一个或多个途径。该发明包括细胞静止和细胞毒性化合物。该发明的方法和组合物特别适用于治疗对其他化疗药物具有抗药性的癌细胞。
• Synthesis, characterization, and relaxation studies of Gd-DO3A conjugate of chlorambucil as a potential theranostic agent
  作者：Jasleen Kaur、Yoanna Tsvetkova、Karim Arroub、Sabri Sahnoun、Fabian Kiessling、Sanjay Mathur

  DOI：10.1111/cbdd.12827

  日期：2017.2

  DO3A-TR-CHL as a non-ionic magnetic contrast agent was tested by performing relaxometric studies on its gadolinium complex. The complex exhibited relaxivities (7.11 mm-1 /s) higher than that of currently used MR contrast agents and showed enhanced contrast in T1 -weighted images. MTT assays revealed that both DO3A-TR-CHL and Gd(III)-DO3A-TR-CHL conjugates exhibited dose-dependent toxicity and an enhanced

  基于DO3A的大环化合物可作为有吸引力的模板，与分子靶向治疗药物偶联后可从中获得临床上有用的治疗剂。在这项研究中，我们描述了新的苯丁酸氮芥（CHL）DO3A共轭物作为磁共振成像（MRI）治疗试剂的化学合成，弛豫和细胞毒性研究。报道了一种方便的合成途径，其允许大环配体（DO3A）通过酪氨酸与化学治疗药物（CHL）结合，以制备有吸引力的螯合药物组合（DO3A-TR-CHL）。所有中间体和最终化合物的结构已通过1 H，13 C NMR和MS确定。通过对relax复合物进行弛豫测量研究，测试了DO3A-TR-CHL作为非离子型磁性对比剂的功效。该复合物表现出比当前使用的MR造影剂高的弛豫度（7.11mm-1 / s），并且在T1加权图像中显示增强的对比度。MTT分析显示，与母体药物（CHL）相比，DO3A-TR-CHL和Gd（III）-DO3A-TR-CHL偶联物均表现出剂量依赖性毒性和增强的抗肿
• Bartolucci; Cellai; Di Filippo, Il Farmaco, 1992, vol. 47, # 11, p. 1367 - 1383
  作者：Bartolucci、Cellai、Di Filippo、Segre、Brufani、Filocamo、Bianco、Guiso、Brizzi、Benedetto、Di Caro、Elia

  DOI：——

  日期：——
• Design, synthesis, and evaluation of estradiol-linked genotoxicants as anti-cancer agents
  作者：U Sharma、J.C Marquis、A Nicole Dinaut、S.M Hillier、B Fedeles、P.T Rye、J.M Essigmann、R.G Croy

  DOI：10.1016/j.bmcl.2004.04.064

  日期：2004.7

  A series of bifunctional compounds was prepared consisting of 17beta estradiol linked to a DNA damaging N,N-bis-(2-chloroethyl)aniline. The objective of our studies was to determine the characteristics of the linker that permitted both reaction with DNA and binding of the resultant covalent adducts to the estrogen receptor. Linker characteristics were pivotal determinants underlying the ability of the compounds to kill selectively breast cancer cells that express the estrogen receptor. (C) 2004 Elsevier Ltd. All rights reserved.
• Facile synthesis of cyclopentapeptide, <i>cyclo</i>[Arg(NO₂)-Gly-Asp(OBn)-<scp>D</scp>-Phe-Lys(Fmoc)], and its application in synthesis of integrin-targeting anticancer conjugate
  作者：Da-You Ma、Tao Zhong、Long-Long Wang、Li-Jun Liu、Ying-Xiong Wang、Su-You Liu

  DOI：10.1080/00397911.2017.1359626

  日期：2017.11.2

  An efficient approach for integrin-targeting cRGDfK conjugate synthesis has been developed using a new protected cyclopentapeptide, cR(NO2)GD(Bn)fK(Fmoc), as the key intermediate. cR(NO2)GD(Bn)fK(Fmoc) was conveniently prepared in high yield. The Fmoc group of this cyclopentapeptide was selectively removed under mild conditions which makes it an ideal intermediate for cRGDfK conjugate synthesis as was well demonstrated in this paper by the synthesis of cRGDfK chlorambucil conjugate.