N-phenyl-N-3-<(2-ethoxycarbonylindolil)> thiourea | 116989-29-8

• 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: N-phenyl-N-3-<(2-ethoxycarbonylindolil)> thiourea
• 英文别名: ethyl 3-(3-phenylthioureido)-1H-indole-2-carboxylate；N-phenyl-N-3-[(2-ethoxycarbonylindolil)] thiourea；ethyl 3-(phenylcarbamothioylamino)-1H-indole-2-carboxylate
• CAS: 116989-29-8
• 化学式: C₁₈H₁₇N₃O₂S
• 分子量: 339.418
• InChiKey: MKCQOXPXPBUMGV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  24
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.11
• 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：

  N-phenyl-N-3-<(2-ethoxycarbonylindolil)> thiourea 在 三乙胺 、 乙酰氯 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 、 potassium hydroxide 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 18.0h， 生成 N-cycloheptyl-2-((4-oxo-3-phenyl-4,5-dihydro-3H-pyrimido[5,4-b]indol-2-yl)thio)acetamide
  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-(2-氰基苯胺基)-乙酸乙酯 在 potassium tert-butylate 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 反应 8.75h， 生成 N-phenyl-N-3-<(2-ethoxycarbonylindolil)> thiourea
  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

• One-step ring-closure procedure for 4,5-dihydro-1,3-thiazino[5,4-b]indole derivatives with Lawesson's reagent. The fifth dihydro-1,3-thiazino[b]indole isomer
  作者：Péter Csomós、Lajos Fodor、Gábor Bernáth、Antal Csámpai、Pál Sohár

  DOI：10.1002/jhet.607

  日期：2011.9

  corresponding 3‐phenylthiourea‐2‐carboxylic acid ester derivatives by chemoselective reduction of the ester group, followed by ring closure under acidic conditions. The structures of the novel products were elucidated by IR, 1H‐NMR, and 13C‐NMR spectroscopy, including 2D‐HMQC, 2D‐HMBC, and DEPT measurements. J. Heterocyclic Chem., (2011).

  我们报告了一种合成新环系统的简便方法：4,5-二氢-1,3-噻嗪基[5,4- b ]吲哚。该程序涉及在二氧化硅存在下使用Lawesson试剂，以实现2-苯甲酰基氨基-3-羟甲基吲哚中间体的一步闭环反应，从而提供4,5-二氢-2--2-芳基-1,3-噻嗪基[ 5,4‐ b ]吲哚。通过相应的3-苯基硫脲-2-羧酸酯衍生物，通过化学选择性还原酯基，然后在酸性条件下闭环，可得到2-苯基亚氨基-1,3-噻嗪[5,4- b ]吲哚。红外，1 H-NMR和13阐明了新产品的结构C-NMR光谱，包括2D-HMQC，2D-HMBC和DEPT测量。J.杂环化​​学。（2011）。
• COMPOSITIONS AND METHODS FOR MODULATING TLR4
  申请人：THE REGENTS OF THE UNIVERSITY OF CALIFORNIA

  公开号：US20150197527A1

  公开（公告）日：2015-07-16

  Provided herein, inter alia, are methods and compositions for modulating TLR-4.

  本文提供了一些调节TLR-4的方法和组合物。
• Russo; Guccione; Santagati, Farmaco, Edizione Scientifica, 1988, vol. 43, # 5, p. 409 - 420
  作者：Russo、Guccione、Santagati、Santagati、Caruso、Leone、Attaguile、Roxas

  DOI：——

  日期：——
• RUSSO, F.;GUCCIONE, S.;SANTAGATI, N. A.;SANTAGATI, A.;CARUSO, A.;LEONE, M+, FARMACO: ED. SCI., 43,(1988) N 5, C. 409-420
  作者：RUSSO, F.、GUCCIONE, S.、SANTAGATI, N. A.、SANTAGATI, A.、CARUSO, A.、LEONE, M+

  DOI：——

  日期：——
• US9505768B2
  申请人：——

  公开号：US9505768B2

  公开（公告）日：2016-11-29