ethyl (2-chloro-3-nitro-6-(trifluoromethyl)pyridin-4-yl)((6-chloropyridin-3-yl)methyl)carbamate | 1338370-95-8

• 分子结构分类: 有机化合物 - 有机1,3-偶极化合物 - 烯丙基型1,3-偶极有机化合物
• 英文名称: ethyl (2-chloro-3-nitro-6-(trifluoromethyl)pyridin-4-yl)((6-chloropyridin-3-yl)methyl)carbamate
• CAS: 1338370-95-8
• 化学式: C₁₅H₁₁Cl₂F₃N₄O₄
• 分子量: 439.178
• InChiKey: YVPHJHVLCUYZQK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.87
• 重原子数：
  28.0
• 可旋转键数：
  5.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  98.46
• 氢给体数：
  0.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  ethyl (2-chloro-3-nitro-6-(trifluoromethyl)pyridin-4-yl)((6-chloropyridin-3-yl)methyl)carbamate 在 盐酸 、 sodium dithionite 、 potassium tert-butylate 、 氨 作用下， 以 2-甲基四氢呋喃 、 乙醇 、 水 为溶剂， 生成 4-amino-1-[[6-(2-pyrrolidin-1-ylethoxy)pyridin-3-yl]methyl]-6-(trifluoromethyl)-3H-imidazo[4,5-c]pyridin-2-one
  参考文献：
  名称：

  Discovery of a highly potent series of TLR7 agonists

  摘要：

  The discovery of a series of highly potent and novel TLR7 agonist interferon inducers is described. Structure- activity relationships are presented, along with pharmacokinetic studies of a lead molecule from this series of N9-pyridylmethyl-8-oxo-3-deazapurine analogues. A rationale for the very high potency observed is offered. An investigation of the clearance mechanism of this class of compounds in rat was carried out, resulting in aldehyde oxidase mediated oxidation being identified as a key component of the high clearance observed. A possible solution to this problem is discussed. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.07.076
• 作为产物：
  描述：

  2-chloro-3-nitro-6-trifluoromethyl-pyridin-4-ylamine 在 potassium carbonate 、 三乙胺 、 sodium iodide 作用下， 以 2-甲基四氢呋喃 、 丙酮 为溶剂， 生成 ethyl (2-chloro-3-nitro-6-(trifluoromethyl)pyridin-4-yl)((6-chloropyridin-3-yl)methyl)carbamate
  参考文献：
  名称：

  Discovery of a highly potent series of TLR7 agonists

  摘要：

  The discovery of a series of highly potent and novel TLR7 agonist interferon inducers is described. Structure- activity relationships are presented, along with pharmacokinetic studies of a lead molecule from this series of N9-pyridylmethyl-8-oxo-3-deazapurine analogues. A rationale for the very high potency observed is offered. An investigation of the clearance mechanism of this class of compounds in rat was carried out, resulting in aldehyde oxidase mediated oxidation being identified as a key component of the high clearance observed. A possible solution to this problem is discussed. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.07.076

文献信息

• Design, Synthesis, and Targeted Delivery of an Immune Stimulant that Selectively Reactivates Exhausted CAR T Cells
  作者：John Victor Napoleon、Boning Zhang、Qian Luo、Madduri Srinivasarao、Philip S. Low

  DOI：10.1002/anie.202113341

  日期：2022.4.4

  Chronic exposure of CAR T cells to tumor antigens can lead to CAR T cell exhaustion and tumor expansion. To reverse this exhaustion, we have developed two orthogonal strategies to target a potent TLR7 agonist specifically to exhausted CAR T cells. We demonstrate here that both strategies rejuvenate exhausted CAR T cells, leading to dramatic reduction in T cell exhaustion markers (PD-1+Tim-3+) and shrinkage

  CAR T 细胞长期暴露于肿瘤抗原可导致 CAR T 细胞耗竭和肿瘤扩张。为了扭转这种疲惫，我们开发了两种正交策略，专门针对用尽的 CAR T 细胞靶向有效的 TLR7 激动剂。我们在此证明，这两种策略都能使衰竭的 CAR T 细胞恢复活力，从而导致 T 细胞衰竭标志物 (PD-1 + Tim-3 + ) 的显着减少和 CAR T 细胞抗性肿瘤的缩小。