4-amino-1-((6-((2-(piperidin-1-yl)ethyl)amino)pyridin-3-yl)methyl)-6-(trifluoromethyl)-1,3-dihydro-2H-imidazo[4,5-c]pyridin-2-one | 1338371-12-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并吡啶类
• 英文名称: 4-amino-1-((6-((2-(piperidin-1-yl)ethyl)amino)pyridin-3-yl)methyl)-6-(trifluoromethyl)-1,3-dihydro-2H-imidazo[4,5-c]pyridin-2-one
• 英文别名: 4-amino-1-[[6-(2-piperidin-1-ylethylamino)pyridin-3-yl]methyl]-6-(trifluoromethyl)-3H-imidazo[4,5-c]pyridin-2-one
• CAS: 1338371-12-2
• 化学式: C₂₀H₂₄F₃N₇O
• 分子量: 435.452
• InChiKey: QKUWZNZVQLRNKN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  31
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  99.4
• 氢给体数：
  3
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  4-amino-1-((6-((2-(piperidin-1-yl)ethyl)amino)pyridin-3-yl)methyl)-6-(trifluoromethyl)-1,3-dihydro-2H-imidazo[4,5-c]pyridin-2-one 在 N,N-二异丙基乙胺 作用下， 以 二甲基亚砜 、 N,N-二甲基甲酰胺 为溶剂， 生成
  参考文献：
  名称：

  [EN] METHODS FOR ENHANCEMENT OF ENGINEERED CELL THERAPIES IN CANCER TREATMENT
  [FR] PROCÉDÉS D'AMÉLIORATION DE THÉRAPIES CELLULAIRES MODIFIÉES DANS LE TRAITEMENT DU CANCER

  摘要：

  提供了一种将M2型巨噬细胞重新编程为M1型巨噬细胞的方法，这可以逆转某些癌症过程中观察到的促炎症到抗炎症的转变，与一种或多种工程细胞（例如CAR T细胞，工程自然杀伤细胞，工程干细胞等）共同使用。这些化合物包括一个免疫调节剂，其靶向细胞的模式识别受体，并通过纳入靶向基团（例如叶酸或其功能性片段或类似物）特异性地作用于感兴趣的细胞。可以包括可释放和/或不可释放的连接剂，并设计为促进免疫调节剂的最佳输送。这些化合物和组合物可以用于一个或多个癌症治疗方法。

  公开号：

  WO2022147576A1
• 作为产物：
  描述：

  benzyl-(2-chloro-3-nitro-6-trifluoromethylpyridin-4-yl)amine 在 盐酸 、 sodium dithionite 、 硫酸 、 氨 、 potassium carbonate 、 三乙胺 、 sodium iodide 作用下， 以 2-甲基四氢呋喃 、 乙醇 、 水 、 丙酮 为溶剂， 生成 4-amino-1-((6-((2-(piperidin-1-yl)ethyl)amino)pyridin-3-yl)methyl)-6-(trifluoromethyl)-1,3-dihydro-2H-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

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。
• WO2021007277A5
  申请人：——

  公开号：WO2021007277A5

  公开（公告）日：2023-07-14
• REJUVENATION OF CAR T CELL
  申请人：Purdue Research Foundation

  公开号：US20210308267A1

  公开（公告）日：2021-10-07

  A payload of drug conjugated to a targeting ligand specifically designed to deliver to exhausted CART cells to rejuvenate these CAR T cells is provided herein. The targeted CAR T cells are modified with a fusion receptor which can bind to the targeting ligand and internalize the conjugated payload of drug to execute its regulatory function to exhausted CAR T cell.
• [EN] COMPOUNDS AND METHODS FOR THE TREATMENT AND PREVENTION OF FIBROTIC DISEASE STATES AND CANCER<br/>[FR] COMPOSÉS ET MÉTHODES POUR LE TRAITEMENT ET LA PRÉVENTION D'ÉTATS DE MALADIE FIBROTIQUE ET DE CANCER
  申请人：PURDUE RESEARCH FOUNDATION

  公开号：WO2021007277A1

  公开（公告）日：2021-01-14

  Compounds, pharmaceutical compositions and methods are provided for reprogramming M2-like macrophages to M1-like macrophages, which reverses the antifibrotic to profibrotic shift observed during the course of fibrotic diseases and certain cancers. The compounds comprise an immune modulator that targets a pattern recognition receptor of a cell and are specific to the cells of interest through the incorporation of a targeting moiety (e.g., folate or a functional fragment or analog thereof). Releasable and/or non-releasable linkers can be included and engineered to facilitate the optimal delivery of the immune modulator. The compounds and compositions can be employed in one or more methods of treatment for fibrotic diseases and/or cancers.
• Discovery of a highly potent series of TLR7 agonists
  作者：Peter Jones、David C. Pryde、Thien-Duc Tran、Fiona M. Adam、Gerwyn Bish、Frederick Calo、Guiseppe Ciaramella、Rachel Dixon、Jonathan Duckworth、David N.A. Fox、Duncan A. Hay、James Hitchin、Nigel Horscroft、Martin Howard、Carl Laxton、Tanya Parkinson、Gemma Parsons、Katie Proctor、Mya C. Smith、Nicholas Smith、Amy Thomas

  DOI：10.1016/j.bmcl.2011.07.076

  日期：2011.10

  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.