ethyl 3-(3-phenethylthioureido)-1H-indole-2-carboxylate | 1171632-04-4

• 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: ethyl 3-(3-phenethylthioureido)-1H-indole-2-carboxylate
• 英文别名: ethyl 3-(2-phenylethylcarbamothioylamino)-1H-indole-2-carboxylate
• CAS: 1171632-04-4
• 化学式: C₂₀H₂₁N₃O₂S
• 分子量: 367.472
• InChiKey: OOSPHFFZKLOZOS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  26
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  98.2
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  ethyl 3-(3-phenethylthioureido)-1H-indole-2-carboxylate 在 polyphosphoric acid 作用下， 以 乙醇 为溶剂， 反应 3.5h， 以61.1%的产率得到3-phenethyl-2-thioxo-2,3-dihydro-1H-pyrimido[5,4-b]indol-4(5H)-one
  参考文献：
  名称：

  Identification of Substituted Pyrimido[5,4-b]indoles as Selective Toll-Like Receptor 4 Ligands

  摘要：

  A cell-based high-throughput screen to identify small molecular weight stimulators of the innate immune system revealed substituted pyrimido[5,4-b]indoles as potent NF kappa beta activators. The most potent hit compound selectively stimulated Toll-like receptor 4 (TLR4) in human and mouse cells. Synthetic modifications of the pyrimido[5,4-b]indole scaffold at the carboxamide, N-3, and N-5 positions revealed differential TLR4 dependent production of NF kappa beta and type I interferon associated cytokines, IL-6 and interferon gamma-induced protein 10 (IP-10) respectively. Specifically, a subset of compounds bearing phenyl and substituted phenyl carboxamides induced lower IL-6 release while maintaining higher IP-10 production, skewing toward the type I interferon pathway. Substitution at N-5 with short alkyl substituents reduced the cytotoxicity of the leading hit compound. Computational studies supported that active compounds appeared to bind primarily to MD-2 in the TLR4/MD-2 complex. These small molecules, which stimulate innate immune cells with minimal toxicity, could potentially be used as adjuvants or immune modulators.

  DOI：

  10.1021/jm301694x
• 作为产物：
  描述：

  2-氨基苯甲腈 在 potassium tert-butylate 、 碳酸氢钠 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 反应 50.75h， 生成 ethyl 3-(3-phenethylthioureido)-1H-indole-2-carboxylate
  参考文献：
  名称：

  Identification of Substituted Pyrimido[5,4-b]indoles as Selective Toll-Like Receptor 4 Ligands

  摘要：

  A cell-based high-throughput screen to identify small molecular weight stimulators of the innate immune system revealed substituted pyrimido[5,4-b]indoles as potent NF kappa beta activators. The most potent hit compound selectively stimulated Toll-like receptor 4 (TLR4) in human and mouse cells. Synthetic modifications of the pyrimido[5,4-b]indole scaffold at the carboxamide, N-3, and N-5 positions revealed differential TLR4 dependent production of NF kappa beta and type I interferon associated cytokines, IL-6 and interferon gamma-induced protein 10 (IP-10) respectively. Specifically, a subset of compounds bearing phenyl and substituted phenyl carboxamides induced lower IL-6 release while maintaining higher IP-10 production, skewing toward the type I interferon pathway. Substitution at N-5 with short alkyl substituents reduced the cytotoxicity of the leading hit compound. Computational studies supported that active compounds appeared to bind primarily to MD-2 in the TLR4/MD-2 complex. These small molecules, which stimulate innate immune cells with minimal toxicity, could potentially be used as adjuvants or immune modulators.

  DOI：

  10.1021/jm301694x

文献信息

• Identification of Substituted Pyrimido[5,4-<i>b</i>]indoles as Selective Toll-Like Receptor 4 Ligands
  作者：Michael Chan、Tomoko Hayashi、Richard D. Mathewson、Afshin Nour、Yuki Hayashi、Shiyin Yao、Rommel I. Tawatao、Brian Crain、Igor F. Tsigelny、Valentina L. Kouznetsova、Karen Messer、Minya Pu、Maripat Corr、Dennis A. Carson、Howard B. Cottam

  DOI：10.1021/jm301694x

  日期：2013.6.13

  A cell-based high-throughput screen to identify small molecular weight stimulators of the innate immune system revealed substituted pyrimido[5,4-b]indoles as potent NF kappa beta activators. The most potent hit compound selectively stimulated Toll-like receptor 4 (TLR4) in human and mouse cells. Synthetic modifications of the pyrimido[5,4-b]indole scaffold at the carboxamide, N-3, and N-5 positions revealed differential TLR4 dependent production of NF kappa beta and type I interferon associated cytokines, IL-6 and interferon gamma-induced protein 10 (IP-10) respectively. Specifically, a subset of compounds bearing phenyl and substituted phenyl carboxamides induced lower IL-6 release while maintaining higher IP-10 production, skewing toward the type I interferon pathway. Substitution at N-5 with short alkyl substituents reduced the cytotoxicity of the leading hit compound. Computational studies supported that active compounds appeared to bind primarily to MD-2 in the TLR4/MD-2 complex. These small molecules, which stimulate innate immune cells with minimal toxicity, could potentially be used as adjuvants or immune modulators.