(2-((4-oxo-3-phenyl-4,5-dihydro-3H-pyrimido[5,4-b]indol-2-yl)thio)acetic acid) | 1438280-85-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯并嘧啶类
• 英文名称: (2-((4-oxo-3-phenyl-4,5-dihydro-3H-pyrimido[5,4-b]indol-2-yl)thio)acetic acid)
• 英文别名: 2-((4-Oxo-3-phenyl-4,5-dihydro-3H-pyrimido[5,4-b]indol-2-yl)thio)acetic acid；2-[(4-oxo-3-phenyl-5H-pyrimido[5,4-b]indol-2-yl)sulfanyl]acetic acid
• CAS: 1438280-85-3
• 化学式: C₁₈H₁₃N₃O₃S
• 分子量: 351.386
• InChiKey: OADDIYIXZWZNCE-UHFFFAOYSA-N

物化性质

• 沸点：
  649.5±61.0 °C(Predicted)
• 密度：
  1.49±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  25
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  111
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (2-((4-oxo-3-phenyl-4,5-dihydro-3H-pyrimido[5,4-b]indol-2-yl)thio)acetic acid) 在 N-甲基吗啉 、 2-氯-4,6-二甲氧基-1,3,5-三嗪 、 三乙胺 、 三氟乙酸 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 42.0h， 生成 1-amino-N-(4-(2-((4-oxo-3-phenyl-4,5-dihydro-3H-pyrimido[5,4-b]indol-2-yl)thio)acetamido)cyclohexyl)-3,6,9,12-tetraoxapentadecan-15-amide
  参考文献：
  名称：

  [EN] POLYMER ADJUVANT
  [FR] ADJUVANT POLYMÈRE

  摘要：

  该发明涉及一种辅助剂，其包括与聚合物链相连的模式识别受体（PRR）激动子分子，这些聚合物链能够在水性条件下形成颗粒，或者在水性条件下响应外部刺激形成颗粒；以及使用这种辅助剂进行疾病治疗或预防的方法。

  公开号：

  WO2016055812A1
• 作为产物：
  描述：

  2-氨基苯甲腈 在 potassium tert-butylate 、 碳酸氢钠 、 乙酰氯 、 potassium hydroxide 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 反应 68.75h， 生成 (2-((4-oxo-3-phenyl-4,5-dihydro-3H-pyrimido[5,4-b]indol-2-yl)thio)acetic acid)
  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

• 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。
• POLYMER ADJUVANT
  申请人：Oxford University Innovation Limited

  公开号：US20170304420A1

  公开（公告）日：2017-10-26

  The invention relates to an adjuvant comprising Pattern Recognition Receptor (PRR) agonist molecules linked to polymer chains that are capable of undergoing particle formation in aqueous conditions, or in aqueous conditions in response to external stimuli; and methods of treatment or prevention of disease using such an adjuvant.
• US9505768B2
  申请人：——

  公开号：US9505768B2

  公开（公告）日：2016-11-29
• METHODS AND COMPOSITIONS FOR TREATING CANCER WITH CANCER-BINDING ADJUVANTS
  申请人：[en]THE UNIVERSITY OF CHICAGO

  公开号：WO2024040169A2

  公开（公告）日：2024-02-22

  Disclosed herein are compositions comprising immune-activating agents that bind the tumor cell surface in the absence of a tumor-targeting protein component. Described herein are methods and compositions for targeting a TLR or STING agonist to tumor cells and/or cells in the tumor microenvironment. It is hypothesized that the metabolic stress of tumor growth also produces an excess of unpaired cysteines on cell surface proteins relative to the rest of the body. Therefore, this chemistry can be used with compounds that would preferentially target unpaired cysteines on cell surface proteins.