11-(N-chlorambucilamino)undecanoic acid | 1260612-37-0

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: 11-(N-chlorambucilamino)undecanoic acid
• 英文别名: N-6-chlorambucil-undecanoic acid；N-6-(chlorambucilyl)undecanoic acid
• CAS: 1260612-37-0
• 化学式: C₂₅H₄₀Cl₂N₂O₃
• 分子量: 487.51
• InChiKey: RKQFYXMRGJWXNX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.01
• 重原子数：
  32.0
• 可旋转键数：
  20.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.68
• 拓扑面积：
  69.64
• 氢给体数：
  2.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  11-(N-chlorambucilamino)undecanoic acid 在 三乙胺 、 N,N'-二环己基碳二亚胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 29.0h， 生成 N-((N-chlorambucilylamino)hexanoyl)-p-hydroxyphenyl-L-p-tyrosinamide
  参考文献：
  名称：

  [EN] ANTICANCER AGENTS BASED ON AMINO ACID DERIVATIVES
  [FR] AGENTS ANTICANCÉREUX À BASE DE DÉRIVÉS D'ACIDES AMINÉS

  摘要：

  本发明提供了以下式（I）的化合物：其中T是L或-A-NH-C（O）-L-；L是-(CH2)n-或-(CH2)p-Z-；A是-(CH2)m-或天然氨基酸的烷基成分；R是-CO2R1，-CH2OH，-C（O）NH（羟基苯基）或C（S）NH（羟基苯基）；R1是H或是C1-C12烷基；X是-OH，OSO2R2，-Cl，-Br或-I；R2是C1-C12烷基或-CF3；Z是苯基或萘基；m是具有值1至20的整数；n是具有值1至20的整数；p是具有值1至20的整数或其对映体，非对映异构体，混合物，药用可接受的盐，溶剂化合物或前药。这些化合物可以用作抗癌剂。

  公开号：

  WO2011011865A1
• 作为产物：
  描述：

  苯丁酸氮芥 在 三乙胺 作用下， 反应 5.0h， 生成 11-(N-chlorambucilamino)undecanoic acid
  参考文献：
  名称：

  Design of novel tyrosine-nitrogen mustard hybrid molecules active against uterine, ovarian and breast cancer cell lines

  摘要：

  L-para-Tyrosine was linked to ortho-hydroxyaniline, meta-hydroxyaniline and para-hydroxyaniline giving three distinct tyrosinamide molecules. The new extended amino acid derivatives were constructed to imitate, in part, the estradiol (E-2, the natural female sex hormone) nucleus. The resulting tyrosinamides were then linked to chlorambucil either directly, or via a 5 and 10 carbon atoms spacer chain. This was done in an attempt to target cancerous cells expressing the estrogen receptor alpha (ER alpha) and to obtain a more specific chemotherapeutic agent. The tyrosinamide-chlorambucil molecules were designed and synthesized in good yields, according to two different approaches. The novel compounds were evaluated for their anticancer efficacy in hormone-dependent and hormone-independent (ER+; MCF-7 and ER-; MDA-MB-231) breast cancer cell lines. Interestingly, the meta-hydroxyphenyl-tyrosinamide-chlorambucil derivatives were more active than the ortho- and para- analogs. The molecules bearing a 5 carbon atoms spacer were selected for additional biological study using a panel of female cancerous cells; breast (ZR-75-1, MDA-MB-436, MDA-MB-468), ovarian (OVCAR-3, A2780) and uterine (Ishikawa, HEC-1A). It was discovered that for breast cancer cells, the new compounds were up to 4.2 times more active than chlorambucil itself. (C) 2011 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.steroids.2011.12.021

文献信息

• SAR study of tyrosine–chlorambucil hybrid regioisomers; synthesis and biological evaluation against breast cancer cell lines
  作者：Caroline Descôteaux、Kevin Brasseur、Valérie Leblanc、Sophie Parent、Éric Asselin、Gervais Bérubé

  DOI：10.1007/s00726-011-1152-3

  日期：2012.8

  receptor negative (ER+ and ER−) breast cancer cell lines revealed an enhanced cytotoxic activity for compounds with the phenol function located at position meta. Molecular docking calculations were performed for the pure l-ortho, l-meta- and l-para-tyrosine phenolic regioisomers. The synthesis of all tyrosine–chlorambucil hybrid regioisomers and their biological activity are reported herein. Possible orientations

  氨基酸被转化并与众所周知的化学治疗剂苯丁酸氮芥偶联，以尝试创造对乳腺癌细胞具有选择性的新抗癌药物。在可用的氨基酸中，酪氨酸被选为雌激素配体。据推测，酪氨酸与雌二醇在结构上有一些相似之处，可能模仿天然激素，随后与雌激素受体结合。在这项探索性研究中，设计了几种酪氨酸-药物偶联物。因此，ortho -、meta - 和paraβ-酪氨酸-苯丁酸氮芥类似物的合成是为了产生具有结构多样性的新型抗癌药物，尤其是在苯酚基团位置方面。这些新的类似物按照有效的合成方法以良好的产率生产。所有酪氨酸-苯丁酸氮芥杂种都比母体药物苯丁酸氮芥更有效。对雌激素受体阳性和雌激素受体阴性（ER +和 ER -）乳腺癌细胞系的体外生物学评估显示，位于meta位置的具有苯酚功能的化合物具有增强的细胞毒活性。对纯l - ortho , l - meta进行了分子对接计算- 和l -对酪氨酸酚区域异构体。本文报道了所有酪氨酸-苯丁
• Synthesis of d- and l-tyrosine-chlorambucil analogs active against breast cancer cell lines
  作者：Caroline Descôteaux、Valérie Leblanc、Kevin Brasseur、Atul Gupta、Éric Asselin、Gervais Bérubé

  DOI：10.1016/j.bmcl.2010.10.039

  日期：2010.12

  A series of D- and L-tyrosine-chlorambucil analogs was synthesized as anticancer drugs for chemotherapy of breast cancer. The novel compounds were synthesized in good yields through efficient modifications of D-and L-tyrosine. The newly synthesized compounds were evaluated for their anticancer efficacy in different hormone-dependent and hormone-independent (ER+ and ER-) breast cancer cell lines. The novel analogs showed significant in vitro anticancer activity when compared to chlorambucil. Structure-activity relationship (SAR) reveals both, the influence of the length of the spacer chain and the stereochemistry of the tyrosine moiety. Interestingly, the D-and L-tyrosinol-chlorambucil derivatives with 10 carbon atoms spacer are selective towards MCF-7 (ER+) breast cancer cell line. (C) 2010 Elsevier Ltd. All rights reserved.