diethyl [1-amine(3-methoxyphenyl)methyl]phosphonate | 1112455-41-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: diethyl [1-amine(3-methoxyphenyl)methyl]phosphonate
• 英文别名: α-O,O'-diethyl amino(3-methoxyphenyl)methylphosphonate；Diethoxyphosphoryl-(3-methoxyphenyl)methanamine
• CAS: 1112455-41-0
• 化学式: C₁₂H₂₀NO₄P
• 分子量: 273.269
• InChiKey: XDVUJTQTLDFOLN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  18
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  70.8
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  diethyl [1-amine(3-methoxyphenyl)methyl]phosphonate 、 大黄酸 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 二甲基亚砜 、 N,N-二甲基甲酰胺 为溶剂， 反应 3.27h， 以87%的产率得到O,O'-diethyl{[(4,5-dihydroxy-9,10-dioxo-9,10-dihydroanthracen-2-yl)formamido](3-methoxyphenyl)methyl}phosphonate
  参考文献：
  名称：

  大黄酸氨基膦酸酯衍生物及其合成方法和应用

  摘要：

  本发明公开了一系列大黄酸氨基膦酸酯衍生物及它们的合成方法和应用。所述大黄酸氨基膦酸酯衍生物的合成方法为：以大黄酸和α-氨基膦酸酯为原料，溶于极性溶剂中，在催化剂HOBT和缩合剂EDAC存在的条件下反应至完全；向反应液中加入三氯甲烷，水洗，收集有机层，上硅胶柱层析，用由体积比为1:4～100的乙酸乙酯和石油醚组成的混合溶剂洗脱，即得到相应的衍生物。所述的大黄酸氨基膦酸酯衍生物，其结构通式如下式(I)所示：其中，R为对溴苯、邻溴苯、间溴苯、对氟苯、邻氟苯、对氯苯、间氯苯、邻氯苯、间甲氧基苯、邻甲氧基苯、苯、萘、对甲氧基苯、间甲基苯、对甲基苯、间氟苯或蒽。

  公开号：

  CN103524555B
• 作为产物：
  描述：

  在 sodium hydroxide 作用下， 以 乙醚 、 水 为溶剂， 反应 2.5h， 生成 diethyl [1-amine(3-methoxyphenyl)methyl]phosphonate
  参考文献：
  名称：

  Synthesis and antitumor activities of novel rhein α-aminophosphonates conjugates

  摘要：

  Several rhein alpha-aminophosphonates conjugates (5a-5q) were synthesized and evaluated for in vitro cytotoxicity against HepG-2, CNE, Spca-2, Hela and Hct-116 cell lines. Some compounds showed relatively high cytotoxicity. Especially, compound 5i exhibited the strongest cytotoxicity against Hct-116 cells (IC50 was 5.32 mu M). All the synthesized compounds exhibited low cytotoxicity against HUVEC cells. The mechanism of compound 5i was preliminarily investigated by Hoechst 33258 staining, JC-1 mitochondrial membrane potential staining and flow cytometry, which indicated that the compound 5i induced apoptosis in Hct-116 cancer cells. Cell cycle analysis showed that these compound 5i mainly arrested Hct-116 cells in G1 stage. The effects of 5i on the activation of caspases expression indicated that 5i might induce apoptosis via the membrane death receptor pathways. In addition, the binding properties of a model analog 5i to DNA were investigated by methods (UV-vis, fluorescence, CD spectroscopy and FRET-melting) in compare with that of rhein. Results indicated that 5i showed moderate ability to interact ct-DNA. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.12.030

文献信息

• Synthesis, antiproliferative and apoptosis-inducing effects of novel asiatic acid derivatives containing α-aminophosphonates
  作者：Ri-Zhen Huang、Cai-Yi Wang、Jian-Fei Li、Gui-Yang Yao、Ying-Ming Pan、Man-Yi Ye、Heng-Shan Wang、Ye Zhang

  DOI：10.1039/c6ra11397d

  日期：——

  This is an Accepted Manuscript, which has been through the RSC Publishing peer review process and has been accepted for publication. Accepted manuscripts are published online shortly after acceptance. This version of the article will be replaced by the fully edited, formatted and proof read Advance Article as soon as this is available.

  这是已接受的手稿，已通过RSC出版同行评审过程，并已被接受出版。接受的手稿在接受后不久就会在线发布。一旦可用，此版本的文章将被完全编辑，格式化并提供高级阅读的高级文章代替。
• Synthesis and antitumor activities of novel α-aminophosphonate derivatives containing an alizarin moiety
  作者：Man-Yi Ye、Gui-Yang Yao、Ying-Ming Pan、Zhi-Xin Liao、Ye Zhang、Heng-Shan Wang

  DOI：10.1016/j.ejmech.2014.02.067

  日期：2014.8

  A series of novel α-aminophosphonate derivatives containing an alizarin moiety (6–7) was designed and synthesized as antitumor agents. MTT (3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide) assay results indicated that most compounds exhibited moderate to high inhibitory activity against KB, NCI-H460, HepG 2, A549, MGC-803, Hct-116, CNE and Hela tumor cell lines. The action mechanism

  一系列含有茜素部分（新颖α-氨基膦衍生物的6 - 7）被设计并作为抗肿瘤剂的合成。MTT（3-（4，5-二甲基噻唑-2-基）-2，5-二苯基溴化四唑）测定结果表明，大多数化合物对KB，NCI-H460，HepG 2，A549，MGC- 803，Hct-116，CNE和Hela肿瘤细胞系。通过荧光染色分析，流式细胞仪分析和实时聚合酶链反应（PCR）分析方法研究了代表性化合物7h，7j和7n的作用机理，这表明这些化合物诱导细胞凋亡并通过增加GSH的产生而参与G1期阻滞。细胞内钙2+和活性氧（ROS）并影响相关的酶和基因。结果表明，这些化合物可通过线粒体依赖性途径诱导细胞凋亡。
• Synthesis and antitumor activities of novel thiourea α-aminophosphonates from dehydroabietic acid
  作者：Xiao-Chao Huang、Meng Wang、Ying-Ming Pan、Gui-Yang Yao、Heng-Shan Wang、Xiao-Yan Tian、Jiang-Ke Qin、Ye Zhang

  DOI：10.1016/j.ejmech.2013.08.055

  日期：2013.11

  levels of antitumor activities against the tested cancer cell lines and that most demonstrated more potent inhibitory activities compared with the commercial anticancer drug 5-fluorouracil. The mechanism of compound 5f was preliminarily investigated by acridine orange/ethidium bromide staining, Hoechst 33258 staining, JC-1 mitochondrial membrane potential staining, TUNEL assay, DNA ladder assay and flow

  设计并合成了一系列具有DHA结构的新型硫脲α-氨基膦酸酯衍生物作为抗肿瘤剂。使用MTT测定法在体外估计了它们对NCI-H460（肺），A549（肺腺癌），HepG2（肝）和SKOV3（卵巢）人癌细胞系的抑制活性。筛选结果表明，许多化合物对测试的癌细胞系均表现出中等至高水平的抗肿瘤活性，并且与市售抗癌药物5-氟尿嘧啶相比，大多数化合物具有更强的抑制活性。化合物5f的作用机理 通过a啶橙/溴化乙锭染色，Hoechst 33258染色，JC-1线粒体膜电位染色，TUNEL测定，DNA阶梯测定和流式细胞术进行了初步研究，表明该化合物可以诱导A549细胞凋亡。
• Al(OTf)₃as an Efficient Catalyst for One-Pot Synthesis of Primary Diethyl 1-Aminophosphonates Under Solvent-Free Conditions
  作者：Sara Sobhani、Zahra Tashrifi

  DOI：10.1080/00397910802369695

  日期：2008.12.16

  A simple and general method has been developed for the one-pot, three-component synthesis of a variety of primary 1-aminophosphonates catalyzed by Al(OTf)(3) under solvent-free conditions in good to high yields.
• Coumarin-containing aminophosphonates bridged with chiral side chain: synthesis and influence of chirality on cytotoxicity and DNA binding
  作者：Ya-Jun Li、Man-Yi Ye、Ri-Zhen Huang、Gui-Yang Yao、Ying-Ming Pan、Zhi-Xin Liao、Heng-Shan Wang

  DOI：10.1007/s00044-013-0899-3

  日期：2014.6

  A series of novel coumarin-containing alpha-aminophosphonates with two chiral centers were synthesized and a single-crystal structure of compound 8g (8g', (R)-diethyl ((S)-2-(4-methyl-2-oxo-2H-chromen-7-yloxy)propanamido)(2-bromophenyl)methylphosphonate) was obtained. The in vitro antitumor activities of compound 8a-8g' against human pulmonary carcinoma cell line (A549), human nasopharyngeal carcinoma (human KB), and human lung adenocarcinoma (MGC-803) cell lines were evaluated. Some compounds showed relatively high cytotoxicity. Compared with 8g, 8g' exhibited an improved activity against three tumor cells, which was evidenced by the IC50 that was four- to five-fold lower than those for 8g. The influence of chirality was also observed in DNA-binding assay of 8g and 8g'. 8g' exhibited higher binding constant (1.96 x 10(3) M-1) as compared to 8g (1.69 x 10(3) M-1).