5-(3-(1H-indol-1-yl)propyl)-N4-butyl-6-methylpyrimidine-2,4-diamine

• 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: 5-(3-(1H-indol-1-yl)propyl)-N4-butyl-6-methylpyrimidine-2,4-diamine
• 英文别名: 4-N-butyl-5-(3-indol-1-ylpropyl)-6-methylpyrimidine-2,4-diamine
• 化学式: C₂₀H₂₇N₅
• 分子量: 337.468
• InChiKey: BNLHNFMOJLMSMB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  25
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  68.8
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  2-氨基-4-氯-6-甲基嘧啶 在 N-碘代丁二酰亚胺 、 copper(l) iodide 、 四(三苯基膦)钯 、 palladium on activated charcoal 、 氢气 、 三乙胺 、 N,N-二异丙基乙胺 作用下， 以 甲醇 、 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 70.0 ℃ 、344.75 kPa 条件下， 反应 41.0h， 生成 5-(3-(1H-indol-1-yl)propyl)-N4-butyl-6-methylpyrimidine-2,4-diamine
  参考文献：
  名称：

  Identification of High-Potency Human TLR8 and Dual TLR7/TLR8 Agonists in Pyrimidine-2,4-diamines

  摘要：

  The induction of toll-like receptor 7 (TLR7)-dependent type I interferons (IFN-alpha/beta) from plasmacytoid dendritic cells as well as the production of TLR8-dependent type II interferon (IFN-y), TNF-alpha, and IL-12 in myeloid dendritic cells are of importance in generating T helper-1 biased adaptive immune responses. In an effort to identify novel dual TLR7/TLR8-active compounds, we undertook structure activity relationship studies in pyrimidine 2,4-diamines, focusing on substituents at CS. Several analogues substituted with aminopropyl appendages at CS displayed dominant TLR8-agonistic activity. N4-Butyl-6-methyl-S-(3morpholinopropyl)pyrimidine-2,4-diamine was found to be a very potent dual TLR7/TLR8 agonist. Employing novel cytokine reporter cell assays, we verified that potency at TLR7 correlates with IFN-alpha/beta production in human blood, whereas IFN-y and TNF-a induction is largely TLR8dependent. Dual TLR7/TLR8 agonists markedly upregulate CD80 expression in multiple dendritic cell subsets, providing insight into the immunological basis for the superior adjuvantic properties of such innate immune stimuli.

  DOI：

  10.1021/acs.jmedchem.6b01860

文献信息

• PYRIMIDINES AND USES THEREOF
  申请人：David Sunil Abraham

  公开号：US20180215720A1

  公开（公告）日：2018-08-02

  The various examples presented herein are directed to compounds of the Formula: wherein R 1 -R 5 are defined herein, and uses of such compounds to, among other things, inhibit an immune response in a subject.

  本文提供的各种示例是针对下述公式的化合物的：其中R1-R5在此处被定义，并且这些化合物的用途包括在其他方面抑制受试者的免疫反应。
• Pyrimidines and uses thereof
  申请人：Regents of the University of Minnesota

  公开号：US10662161B2

  公开（公告）日：2020-05-26

  The various examples presented herein are directed to compounds of the Formula: wherein R1-R5 are defined herein, and uses of such compounds to, among other things, inhibit an immune response in a subject.

  本文介绍的各种示例均针对式化合物： 其中 R1-R5 在本文中定义，以及此类化合物在抑制受试者免疫反应等方面的用途。