N-cyclohexyl-2-(7,9-dimethoxy-2,8-dioxo-4-phenyl-3-(4-(trifluoromethyl)phenyl)-1-azaspiro[4.5]deca-3,6,9-trien-1-yl)-2-(2,3,4-trimethoxyphenyl)acetamide

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 二苯乙烯类
• 英文名称: N-cyclohexyl-2-(7,9-dimethoxy-2,8-dioxo-4-phenyl-3-(4-(trifluoromethyl)phenyl)-1-azaspiro[4.5]deca-3,6,9-trien-1-yl)-2-(2,3,4-trimethoxyphenyl)acetamide
• 英文别名: N-cyclohexyl-2-[7,9-dimethoxy-2,8-dioxo-4-phenyl-3-[4-(trifluoromethyl)phenyl]-1-azaspiro[4.5]deca-3,6,9-trien-1-yl]-2-(2,3,4-trimethoxyphenyl)acetamide
• 化学式: C₄₁H₄₁F₃N₂O₈
• 分子量: 746.78
• InChiKey: MHUNMTYDVYCIEV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.1
• 重原子数：
  54
• 可旋转键数：
  11
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.34
• 拓扑面积：
  113
• 氢给体数：
  1
• 氢受体数：
  11

反应信息

• 作为产物：
  描述：

  2,3,4-三甲氧基苯甲醛 在 四(三苯基膦)钯 、 碘 、 sodium carbonate 作用下， 以 水 、 甲苯 、 乙腈 为溶剂， 反应 6.0h， 生成 N-cyclohexyl-2-(7,9-dimethoxy-2,8-dioxo-4-phenyl-3-(4-(trifluoromethyl)phenyl)-1-azaspiro[4.5]deca-3,6,9-trien-1-yl)-2-(2,3,4-trimethoxyphenyl)acetamide
  参考文献：
  名称：

  通过一站式串联Ugi 4CC /亲电ipso-碘环化反应，高效构建Azaspiro [4.5] trienone库。

  摘要：

  通过进行串联Ugi四组分缩合（U4CC）（涉及取代的对茴香胺，醛，3-烷基/芳基丙酸和异氰酸酯）的串联Ugi四联缩合反应，开发了药物学上重要的氮杂螺并[4.5]三烯酮的溶液相平行合成方法，以及一锅碘介导的碘化碘化。这种高度原子经济的方法生产的官能化氮杂螺并[4.5]三烯酮的总收率好至极好，并且沉淀后结晶容易分离出产物。这些带有乙烯基碘的氮杂螺环[4.5]三烯酮可通过Suzuki偶联和脱碘反应用于进一步修饰，以证明这些产品适用于各种钯催化的修饰。本方法提供了易于获得的高度功能化氮杂螺[4]。

  DOI：

  10.1021/acscombsci.5b00065

文献信息

• Efficient Construction of Azaspiro[4.5]trienone Libraries via Tandem Ugi 4CC/Electrophilic <i>ipso</i>-Iodocyclization in One-Pot
  作者：D. Yugandhar、Ajay Kumar Srivastava

  DOI：10.1021/acscombsci.5b00065

  日期：2015.8.10

  excellent overall yields and products were easily isolated by precipitation followed by crystallization. These vinyl-iodide bearing azaspiro[4.5]trienones were utilized for further modifications through Suzuki coupling and deiodination reaction to demonstrate the suitability of these products for various palladium catalyzed modifications. The present method provides an easy access to highly functionalized

  通过进行串联Ugi四组分缩合（U4CC）（涉及取代的对茴香胺，醛，3-烷基/芳基丙酸和异氰酸酯）的串联Ugi四联缩合反应，开发了药物学上重要的氮杂螺并[4.5]三烯酮的溶液相平行合成方法，以及一锅碘介导的碘化碘化。这种高度原子经济的方法生产的官能化氮杂螺并[4.5]三烯酮的总收率好至极好，并且沉淀后结晶容易分离出产物。这些带有乙烯基碘的氮杂螺环[4.5]三烯酮可通过Suzuki偶联和脱碘反应用于进一步修饰，以证明这些产品适用于各种钯催化的修饰。本方法提供了易于获得的高度功能化氮杂螺[4]。
• Identification of novel β-lactams and pyrrolidinone derivatives as selective Histamine-3 receptor (H3R) modulators as possible anti-obesity agents
  作者：Anirban Ghoshal、Ajeet Kumar、Doddapaneni Yugandhar、Chandan Sona、Sunu Kuriakose、Kommu Nagesh、Mamunur Rashid、Sandeep K. Singh、Muhammad Wahajuddin、Prem N. Yadav、Ajay K. Srivastava

  DOI：10.1016/j.ejmech.2018.04.020

  日期：2018.5

  Four series of structurally related beta-lactams, 2,5-pyrrolidinediones, azaspirodecatrienediones (ASDT) and dihydropyrroloquinoxalinetriones (DPQT) were synthesized by utilizing post-Ugi modifications in one pot, and their activity towards human histamine-3 receptor (H3R) was evaluated. Out of 94 compounds, screened against histamine-3 receptor (H3R), 21 compounds showed high H3R selective agonist property with EC50 values ranging from 187 nM to 0.1 nM, whereas none of the compound was found to have the affinity towards other receptors of histamine family such as histamine HI, H2, and H4 receptor. All active compounds have no assay interference activity as determined by in-silico analysis and receptor independent luciferase assay and cell cytotoxicity assay. Given the important role of H3R in hypophagia, we also evaluated the in vivo effect of the representative compound 6k on the cumulative food intake in diet induce obese C57BL6/J mice. Interestingly, we observed that single dose administration (20 mg/kg, intraperitoneal injection) of 6k significantly suppressed cumulative food intake, while no significant effect was observed at 10 mg/kg. These results suggest that beta-lactams, 2,5-pyrrolidinediones, azaspirodecatrienediones (ASDT) and dihydropyrroloquinoxalinetriones (DPQT) could be useful for the development of anti-obesity candidate drugs. (C) 2018 Elsevier Masson SAS. All rights reserved.