ethyl 2-amino-7-hydroxy-4-(3,4-dimethoxyphenyl)-4H-chromene-3-carboxylate | 401464-02-6

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 新黄酮类化合物
• 英文名称: ethyl 2-amino-7-hydroxy-4-(3,4-dimethoxyphenyl)-4H-chromene-3-carboxylate
• 英文别名: ethyl 2-amino-4-(3,4-dimethoxyphenyl)-7-hydroxy-4H-chromene-3-carboxylate
• CAS: 401464-02-6
• 化学式: C₂₀H₂₁NO₆
• 分子量: 371.39
• InChiKey: REBVQASAMYDXIF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  27
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  100
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  ethyl 2-amino-7-hydroxy-4-(3,4-dimethoxyphenyl)-4H-chromene-3-carboxylate 在 一水合肼 作用下， 以 甲醇 为溶剂， 以71 %的产率得到2‐amino‐4‐(3,4‐dimethoxyphenyl)‐7‐hydroxy‐4H‐chromene‐3‐carbohydrazide
  参考文献：
  名称：

  设计、合成新型基于色烯的肝细胞癌支架：细胞周期阻滞、对耐药癌细胞的细胞毒作用、细胞凋亡诱导和 c-Src 抑制

  摘要：

  基于4-(3,4-二甲氧基) -4H-色烯骨架合成了新的色烯衍生物。所有目标化合物均表现出针对 HepG2 细胞的细胞毒活性 (IC 50 = 2.40–141.22 μM)。 Chromens 5和9的细胞毒性优于十字孢菌素 (IC 50 = 18.27 μM) 和长春花碱 (IC 50 = 5.20 μM)。化合物5和9的 c-Src 激酶抑制测定显示， 5 (IC 50 = 0.184 μM) 的 c-Src 抑制活性优于9 (IC 50 = 0.288 μM)。最有效的化合物5针对正常 WI-38 细胞的安全性通过其 IC 50为 115.75 μM 与 5-FU 相当（IC 50 = 16.28 μM）得到证实。此外，有前途的色烯5对耐药 HepG2 细胞表现出有效的细胞毒性，IC 50为 26.03 μM，与 5-FU (IC 50 = 42.68 μM) 相当。最活跃的色烯5将

  DOI：

  10.1002/ddr.22133
• 作为产物：
  描述：

  3,4-二甲氧基苯甲醛 、 氰乙酸乙酯 在 哌啶 作用下， 以 乙醇 为溶剂， 反应 8.0h， 生成 ethyl 2-amino-7-hydroxy-4-(3,4-dimethoxyphenyl)-4H-chromene-3-carboxylate
  参考文献：
  名称：

  Optimisation of estrogen receptor subtype-selectivity of a 4-Aryl-4H-chromene scaffold previously identified by virtual screening

  摘要：

  4-Aryl-4H-Chromene derivatives have been previously shown to exhibit anti-proliferative, apoptotic and anti-angiogenic activity in a variety of tumor models in vitro and in vivo generally via activation of caspases through inhibition of tubulin polymerisation. We have previously identified by Virtual Screening (VS) a 4-aryl-4H-chromene scaffold, of which two examples were shown to bind Estrogen Receptor alpha and beta with low nanomolar affinity and <20-fold selectivity for alpha over beta and low micromolar anti-proliferative activity in the MCF-7 cell line. Thus, using the 4-aryl-4H-chromene scaffold as a starting point, a series of compounds with a range of basic arylethers at C-4 and modifications at the C3-ester substituent of the benzopyran ring were synthesised, producing some potent ER antagonists in the MCF-7 cell line which were highly selective for ERa (compound 35; 350-fold selectivity) or ER beta (compound 42; 170-fold selectivity).

  DOI：

  10.1016/j.bmc.2019.115261

文献信息

• Optimisation of estrogen receptor subtype-selectivity of a 4-Aryl-4H-chromene scaffold previously identified by virtual screening
  作者：Miriam Carr、Andrew J.S. Knox、Daniel K. Nevin、Niamh O'Boyle、Shu Wang、Billy Egan、Thomas McCabe、Brendan Twamley、Daniela M. Zisterer、David G. Lloyd、Mary J. Meegan

  DOI：10.1016/j.bmc.2019.115261

  日期：2020.3

  4-Aryl-4H-Chromene derivatives have been previously shown to exhibit anti-proliferative, apoptotic and anti-angiogenic activity in a variety of tumor models in vitro and in vivo generally via activation of caspases through inhibition of tubulin polymerisation. We have previously identified by Virtual Screening (VS) a 4-aryl-4H-chromene scaffold, of which two examples were shown to bind Estrogen Receptor alpha and beta with low nanomolar affinity and <20-fold selectivity for alpha over beta and low micromolar anti-proliferative activity in the MCF-7 cell line. Thus, using the 4-aryl-4H-chromene scaffold as a starting point, a series of compounds with a range of basic arylethers at C-4 and modifications at the C3-ester substituent of the benzopyran ring were synthesised, producing some potent ER antagonists in the MCF-7 cell line which were highly selective for ERa (compound 35; 350-fold selectivity) or ER beta (compound 42; 170-fold selectivity).
• Design, synthesis of novel chromene‐based scaffolds targeting hepatocellular carcinoma: Cell cycle arrest, cytotoxic effect against resistant cancer cells, apoptosis induction, and c‐Src inhibition
  作者：Eman K. A. Abdelall、Heba A. H. Elshemy、Madlen B. Labib、Fatma E. A. Mohamed

  DOI：10.1002/ddr.22133

  日期：2024.2

  normal WI-38 cells was confirmed via its IC50 of 115.75 μM comparable with 5-FU (IC50 = 16.28 μM). Moreover, the promising chromene 5 displayed potent cytotoxicity against resistant HepG2 cells with IC50 of 26.03 μM comparable with 5-FU (IC50 = 42.68 μM). The most active chromene 5 arrested the HepG2 cell cycle at the S phase and induced a 29-fold increase in the total number of apoptotic cells indicating

  基于4-(3,4-二甲氧基) -4H-色烯骨架合成了新的色烯衍生物。所有目标化合物均表现出针对 HepG2 细胞的细胞毒活性 (IC 50 = 2.40–141.22 μM)。 Chromens 5和9的细胞毒性优于十字孢菌素 (IC 50 = 18.27 μM) 和长春花碱 (IC 50 = 5.20 μM)。化合物5和9的 c-Src 激酶抑制测定显示， 5 (IC 50 = 0.184 μM) 的 c-Src 抑制活性优于9 (IC 50 = 0.288 μM)。最有效的化合物5针对正常 WI-38 细胞的安全性通过其 IC 50为 115.75 μM 与 5-FU 相当（IC 50 = 16.28 μM）得到证实。此外，有前途的色烯5对耐药 HepG2 细胞表现出有效的细胞毒性，IC 50为 26.03 μM，与 5-FU (IC 50 = 42.68 μM) 相当。最活跃的色烯5将