4-[4-[bis(2-chloroethyl)amino]phenyl]-N-[(2S)-1-(2-hydroxyanilino)-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]butanamide | 1263819-87-9

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 4-[4-[bis(2-chloroethyl)amino]phenyl]-N-[(2S)-1-(2-hydroxyanilino)-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]butanamide
• CAS: 1263819-87-9
• 化学式: C₂₉H₃₃Cl₂N₃O₄
• 分子量: 558.505
• InChiKey: MJNBQKRNQHOOMV-SANMLTNESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  38
• 可旋转键数：
  14
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  102
• 氢给体数：
  4
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  Boc-L-酪氨酸 在 1-羟基苯并三唑 、 三乙胺 、 N,N'-二环己基碳二亚胺 、 三氟乙酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 76.0h， 生成 4-[4-[bis(2-chloroethyl)amino]phenyl]-N-[(2S)-1-(2-hydroxyanilino)-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]butanamide
  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

• Design of novel tyrosine-nitrogen mustard hybrid molecules active against uterine, ovarian and breast cancer cell lines
  作者：Caroline Descôteaux、Kevin Brasseur、Valérie Leblanc、Sophie Parent、Éric Asselin、Gervais Bérubé

  DOI：10.1016/j.steroids.2011.12.021

  日期：2012.4

  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.