N-hydroxy-3-(4(((2-(2-methyl-1H-indol-3-yl)ethyl)amino)methyl)phenyl)propanamide

• 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-hydroxy-3-(4(((2-(2-methyl-1H-indol-3-yl)ethyl)amino)methyl)phenyl)propanamide
• 英文别名: N-hydroxy-3-[4-[[[2-(2-methyl-1H-indol-3-yl)-ethyl]-amino]methyl]phenyl]-2E-2-propenamide；N-hydroxy-3-(4-(((2-(2-methyl-1h-indol-3-yl)ethyl)amino)methyl)phenyl)propanamide；N-hydroxy-3-[4-[[2-(2-methyl-1H-indol-3-yl)ethylamino]methyl]phenyl]propanamide
• 化学式: C₂₁H₂₅N₃O₂
• 分子量: 351.448
• InChiKey: AAHLLMGAWIHICC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  26
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  77.2
• 氢给体数：
  4
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  1H-2-甲基-3-氨乙基吲哚 在 sodium cyanoborohydride 、 N,N-二异丙基乙胺 、 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 乙醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 41.0h， 生成 N-hydroxy-3-(4(((2-(2-methyl-1H-indol-3-yl)ethyl)amino)methyl)phenyl)propanamide
  参考文献：
  名称：

  Identifying drug targets in tissues and whole blood with thermal-shift profiling

  摘要：

  监测药物与靶标的相互作用，采用如细胞热迁移测定（CETSA）等方法在简单细胞系统中已得到广泛应用，但在体内依然具有挑战性。在此我们介绍了一种组织热蛋白组分析（tissue-TPP），该方法通过定量质谱检测药物处理动物的组织样本中蛋白质热稳定性的变化，来测量小分子药物与组织中蛋白质的结合。我们报告了器官特异性、蛋白组范围的热稳定性图谱，并推导出非共价组蛋白去乙酰化酶抑制剂panobinostat在大鼠肝脏、肺、肾脏和脾脏中的靶标谱，以及B-Raf抑制剂vemurafenib在小鼠睾丸中的靶标谱。此外，我们设计了血液CETSA和血液TPP，并将其应用于直接在全血中测量panobinostat和BET家族抑制剂JQ1的靶标和非靶标结合。panobinostat的血液TPP分析确认了其与已知靶标的结合，还揭示了锌指转录因子ZNF512的热稳定性增强。这些方法将有助于阐明药物在体内的作用机制。小分子药物的靶标在组织和血液中通过热蛋白组测定被检测到。

  DOI：

  10.1038/s41587-019-0388-4

文献信息

• Antibody molecules to PD-1 and uses thereof
  申请人：NOVARTIS AG

  公开号：US10752687B2

  公开（公告）日：2020-08-25

  Antibody molecules that specifically bind to PD-1 are disclosed. The anti-PD-1 antibody molecules can be used to treat, prevent and/or diagnose cancerous or infectious conditions and disorders.

  本研究公开了与 PD-1 特异性结合的抗体分子。抗 PD-1 抗体分子可用于治疗、预防和/或诊断癌症或感染性疾病。
• Compositions and methods for activating “stimulator of interferon gene”13 dependent signalling
  申请人：CHINOOK THERAPEUTICS, INC.

  公开号：US11040053B2

  公开（公告）日：2021-06-22

  The present invention provides highly active cyclic-di-nucleotide (CDN) immune stimulators that activate DCs via a recently discovered cytoplasmic receptor known as STING (Stimulator of Interferon Genes). In particular, the CDNs of the present invention are provided in the form of a composition comprising one or more cyclic purine dinucleotides induce human STING-dependent type I interferon production, wherein the cyclic purine dinucleotides present in the composition are 2′-fluoro substituted, bis-3′,5′ CDNs, and most preferably one or more 2′,2″-diF-Rp,Rp, bis-3′,5′CDNs.

  本发明提供了高活性环状二核苷酸（CDN）免疫刺激剂，可通过最近发现的一种称为 STING（干扰素基因刺激器）的细胞质受体激活 DC。特别是，本发明的 CDN 以组合物的形式提供，该组合物包含一种或多种环状嘌呤二核苷酸，可诱导人类 STING 依赖性 I 型干扰素的产生、其中组合物中的环状嘌呤二核苷酸是 2′-氟取代的双-3′,5′CDN，最优选的是一种或多种 2′,2″-diF-Rp,Rp，双-3′,5′CDN。
• ANTIBODY MOLECULES TO PD-1 AND USES THEREOF
  申请人：NOVARTIS AG

  公开号：US20180155427A1

  公开（公告）日：2018-06-07

  Antibody molecules that specifically bind to PD-1 are disclosed. The anti-PD-1 antibody molecules can be used to treat, prevent and/or diagnose cancerous or infectious conditions and disorders.
• COMPOSITIONS AND METHODS FOR ACTIVATING "STIMULATOR OF INTERFERON GENE" - DEPENDENT SIGNALLING
  申请人：ADURO BIOTECH, INC.

  公开号：US20200179431A1

  公开（公告）日：2020-06-11

  The present invention provides highly active cyclic-di-nucleotide (CDN) immune stimulators that activate DCs via a recently discovered cytoplasmic receptor known as STING (Stimulator of Interferon Genes). In particular, the CDNs of the present invention are provided in the form of a composition comprising one or more cyclic purine dinucleotides induce human STING-dependent type I interferon production, wherein the cyclic purine dinucleotides present in the composition are 2′-fluoro substituted, bis-3′,5′ CDNs, and most preferably one or more 2′,2″-diF-Rp,Rp, bis-3′,5′CDNs.
• COMPOUNDS AND METHODS FOR IMPROVING IMPAIRED ENDOGENOUS FIBRINOLYSIS USING HISTONE DEACETYLASE INHIBITORS
  申请人：Cereno Scientific AB

  公开号：US20210060014A1

  公开（公告）日：2021-03-04

  There is provided a compound which is a histone deacetylase (HDAC) inhibitor, or a pharmaceutically acceptable ester, amide, solvate or salt thereof, for use in: (I) treating or preventing a pathological condition associated with excess fibrin deposition and/or thrombus formation; and/or (II) potentiating the degradation of fibrin deposits and preventing such deposits associated with pathological conditions or which may lead to such conditions, wherein the HDAC inhibitor, and the dose thereof, is as described in the description. There is also provided valproic acid, or a pharmaceutically acceptable salt thereof, for use in improving or normalizing endogenous fibrinolysis impaired by local or systemic inflammation.