methyl 2-(5-iodo-1H-indol-3-yl)-2-oxoacetate | 374818-69-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: methyl 2-(5-iodo-1H-indol-3-yl)-2-oxoacetate
• CAS: 374818-69-6
• 化学式: C₁₁H₈INO₃
• 分子量: 329.094
• InChiKey: DLRNETFPKOBMCS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  59.2
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  methyl 2-(5-iodo-1H-indol-3-yl)-2-oxoacetate 在 咪唑 、 copper(l) iodide 、 四(三苯基膦)钯 、 N,N-二甲基甘氨酸 、 偶氮二甲酸二异丙酯 、 dimethyl sulfide borane 、 potassium carbonate 、 叔丁基二甲基氯硅烷 、 三苯基膦 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 79.5h， 生成 2-[2-[1-[4-(2,6-dichlorophenyl)phenyl]-5-(4-fluorophenyl)indol-3-yl]ethoxy]benzoic acid
  参考文献：
  名称：

  发现取代的吲哚衍生物作为 m6A-RNA 甲基转移酶 METTL3-14 复合物的变构抑制剂

  摘要：

  m 6 RNA 甲基转移酶 (METTL3-14) 催化 mRNA 中腺苷的甲基化并在 mRNA 功能中发挥重要作用，它与多种癌症的进展有关，包括急性髓性白血病 (AML)。在这项研究中，我们描述了基于构效关系 (SAR) 的 METTL3-14 复合物的第一个变构抑制剂的发现和命中化合物 4-[2-[5-chloro-1-(diphenylmethyl) 的优化研究。 )-2-甲基-1H-吲哚-3-基]-乙氧基]苯甲酸 (CDIBA)。化合物43n在结构的 4 个不同区域的修饰中进行了优化，并显示出 METTL3-14 复合物的有效酶抑制活性（IC 50 = 2.81 μM)，并通过抑制 m 6 A mRNA 水平在 AML 细胞系中发挥抗增殖作用。43n的抑制机制和结合模式基于变构位点的可逆和非竞争性抑制谱的相互作用以及 METTL3-14 复合物相对于每个亚基酶​​或截短复合酶的选择性。

  DOI：

  10.1002/ddr.21910
• 作为产物：
  描述：

  2-(5-iodo-1H-indol-3-yl)-2-oxoacetyl chloride 、 sodium methylate 在 甲醇 作用下， 以 乙醚 为溶剂， 以553 mg的产率得到methyl 2-(5-iodo-1H-indol-3-yl)-2-oxoacetate
  参考文献：
  名称：

  Labeled 3-aryl-4-indolylmaleimide derivatives and their potential as angiogenic PET biomarkers

  摘要：

  In a continued effort to find a suitable PET tracer for visualization of angiogenic processes, we explored the 3,4-diarylmaleimide family, known to have high affinity and selectivity towards the VEGFR-TKs. One previously reported agent and three new halogen-containing 3,4-diarylmaleimide derivatives were synthesized. The four maleimide derivatives were evaluated for their affinity and selectivity towards the VEGFRs and exhibited promising results. An automated carbon-11 radiolabeling route with a total synthesis time of 50 min successfully labeled the lead compound, resulting in 1.55 +/- 0.15 GBq of tracer with a radiochemical yield of 20 +/- 2%, 96% radiochemical purity and a SA of 111 +/- 22 GBq/mu mol (EOB, n = 5). The tracer possessed high stability in in vitro blood stability tests and specific VEGFR-TK binding profiles in intact cell binding experiments. Tracer lipophilicity was evaluated in an n-octanol/phosphate buffer system giving a Log D-7.4 of 1.99 +/- 0.04. For the in vivo experiments, two animal models were used. The first was a U87 glioma tumor model, frequently reported in the literature and the second, a newly developed 293/KDR tumor model. Both models were validated for VEGFR-2 expression and used in in vivo biodistribution studies. These studies revealed low accumulation and rapid washout of the tracer from tumor tissue. High accumulation of activity in the liver prompted us to examine the tracer's in vitro stability to liver microsomes, revealing low resistance to P450 metabolism. In spite of encouraging in vitro results, the labeled lead tracer failed to accumulate in VEGFR-2 overexpressing tumors. It is possible that poor resistance to P450 metabolism reduces tracer's circulation leading to low tumor accumulation. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2009.12.004

文献信息

• Neuroprotective and anti-proliferative compounds
  申请人：——

  公开号：US20040102467A1

  公开（公告）日：2004-05-27

  This invention features ring-substituted pyrrolo-&bgr;-carboline derivatives and ring-substitution and structural derivatives of 3-(1H-indol-3-yl)-1H-pyrrole-2,5-dione of formulas (I-III), which are useful as neuroprotective and anti-proliferative compounds. Also disclosed are methods for the preparation of these compounds, selected biological profiles and uses of these compounds in the treatment of various neurodegenerative and inflammatory diseases of the human nervous system and in the treatment of various other proliferative disorders characterized by loss of growth or cellular differentiation control including, but not limited to, cancer and inflammation. 1

  这项发明涉及环取代吡咯β-咔啉衍生物和3-(1H-吲哚-3-基)-1H-吡咯-2,5-二酮的环取代和结构衍生物，其作为神经保护和抗增殖化合物具有用途。还公开了这些化合物的制备方法，选择的生物学特性以及这些化合物在治疗人类神经系统的各种神经退行性和炎症性疾病以及治疗其他各种增殖性疾病中的用途，这些疾病的特征是失去生长或细胞分化控制，包括但不限于癌症和炎症。
• NEUROPROTECTIVE AND ANTI-PROLIFERATIVE COMPOUNDS
  申请人：Aegera Therapeutics Inc.

  公开号：EP1283836A2

  公开（公告）日：2003-02-19
• US7129250B2
  申请人：——

  公开号：US7129250B2

  公开（公告）日：2006-10-31
• [EN] NEUROPROTECTIVE AND ANTI-PROLIFERATIVE COMPOUNDS<br/>[FR] COMPOSÉS NEUROPROTECTEURS ET ANTI-PROLIFÉRATIFS
  申请人：AEGERA THERAPEUTICS INC

  公开号：WO2001087887A2

  公开（公告）日：2001-11-22

  This invention features ring-substituted pyrrolo-β-carboline derivatives and ring-substitution and structural derivatives of 3-(1H-indol-3-yl)-1H-pyrrole-2,5-dione of formulas (I - III), which are useful as neuroprotective and anti-proliferative compounds. Also disclosed are methods for the preparation of these compounds, selected biological profiles and uses of these compounds in the treatment of various neurodegenerative and inflammatory diseases of the human nervous system and in the treatment of various other proliferative disorders characterized by loss of growth or cellular differentiation control including, but not limited to, cancer and inflammation.