2-(tetrahydrofuran-2-yl)aniline | 1384979-47-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 2-(tetrahydrofuran-2-yl)aniline
• 英文别名: 2-Tetrahydrofuran-2-yl-aniline；2-(oxolan-2-yl)aniline
• CAS: 1384979-47-8
• 化学式: C₁₀H₁₃NO
• 分子量: 163.219
• InChiKey: IHKGQAUPMXBYBL-UHFFFAOYSA-N

物化性质

• 沸点：
  278.9±33.0 °C(Predicted)
• 密度：
  1.116±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  12
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  35.2
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-(tetrahydrofuran-2-yl)aniline 在 N-溴代丁二酰亚胺(NBS) 作用下， 生成 C₁₀H₁₂BrNO
  参考文献：
  名称：

  Evaluation of WO2012177707 and WO2012097269: Vertex's phosphate prodrugs of gyrase and topoisomerase antibacterial agents

  摘要：

  The two patent applications describe two novel compounds in the benzimidazole class of GyrB/ParE antibacterial agents and multiple phosphate prodrugs derived from these compounds. The new benzimidazole compounds have excellent antibacterial activity on Gram-positive strains. But like previous benzimidazoles, they have limited solubility and are highly protein bound. The phosphate prodrugs offer a drug substance with high aqueous solubility that should aid both intravenous and oral formulations. The potential utility of the prodrugs was demonstrated in efficacy studies.

  DOI：

  10.1517/13543776.2013.820707
• 作为产物：
  描述：

  1-溴-2-硝基苯 在 5%-palladium/activated carbon 、 palladium diacetate 1,3-双(二苯基膦)丙烷 、 氢气 、 potassium carbonate 、 三乙胺 作用下， 以 1,4-二氧六环 、 甲醇 为溶剂， 生成 2-(tetrahydrofuran-2-yl)aniline
  参考文献：
  名称：

  SOLID FORMS OF GYRASE INHIBITOR (R)-1-ETHYL-3-[5-[2-(1-HYDROXY-METHYL-ETHYL)PYRIMIDIN-5-YL]-7-(TETRAHYDROFURAN-2-YL)-1H-BENZIMIDAZOL-2-YL]UREA

  摘要：

  本申请涉及公式（I）化合物的固态形式及其药用盐，这些化合物和盐能抑制细菌旋转酶和/或Topo IV，以及包含这些化合物和盐的药物组合物。这些化合物和盐在治疗细菌感染中具有用途。

  公开号：

  US20120184741A1

文献信息

• Discovery of Diaminopyrimidine Carboxamide HPK1 Inhibitors as Preclinical Immunotherapy Tool Compounds
  作者：Brandon A. Vara、Samuel M. Levi、Abdelghani Achab、David A. Candito、Xavier Fradera、Charles A. Lesburg、Shuhei Kawamura、Brian M. Lacey、Jongwon Lim、Joey L. Methot、Zangwei Xu、Haiyan Xu、Dustin M. Smith、Jennifer A. Piesvaux、J. Richard Miller、Mark Bittinger、Sheila H. Ranganath、David J. Bennett、Erin F. DiMauro、Alexander Pasternak

  DOI：10.1021/acsmedchemlett.1c00096

  日期：2021.4.8

  production as well as tumor growth inhibition in vivo, supporting its value as an immunotherapeutic target. Herein, we present the structurally enabled discovery of novel, potent, and selective diaminopyrimidine carboxamide HPK1 inhibitors. The key discovery of a carboxamide moiety was essential for enhanced enzyme inhibitory potency and kinome selectivity as well as sustained elevation of cellular IL-2

  造血祖细胞激酶 1 (HPK1) 是一种丝氨酸/苏氨酸激酶，是 T 细胞受体 (TCR) 和 B 细胞信号传导的负免疫调节因子，主要在造血细胞中表达。因此，据报道，在 HPK1 激酶死亡的同基因小鼠模型中，HPK1 功能丧失显示出增强的 T 细胞信号传导和细胞因子产生以及体内肿瘤生长抑制，支持其作为免疫治疗靶点的价值。在此，我们提出了新型、有效、选择性二氨基嘧啶甲酰胺 HPK1 抑制剂的结构发现。甲酰胺部分的关键发现对于增强酶抑制效力和激酶组选择性以及在人外周血单核细胞的滴定范围内持续提高细胞 IL-2 产量至关重要。使用各种悬垂氨基环系统阐明结构-活性关系，可以鉴定出几种具有良好体外前景的小分子 I 型抑制剂。
• PROCESS OF MAKING GYRASE AND TOPOISOMERASE IV INHIBITORS
  申请人：Shannon Dean

  公开号：US20120184742A1

  公开（公告）日：2012-07-19

  The present application is directed to compounds, intermediates and methods for preparing compounds of formula (I) or a pharmaceutically acceptable salts thereof, wherein R is H or F, and each of R 3 , R 4 , and R 5 are as defined herein. The compounds of formula (I) and pharmaceutical compositions comprising said compounds and salts inhibit bacterial gyrase and/or Topo IV and are useful in treating bacterial infections.

  本申请涉及化合物、中间体和制备公式（I）化合物或其药学上可接受的盐的方法，其中R为H或F，R3、R4和R5如本文所定义。公式（I）化合物及包含该化合物和盐的药物组合物抑制细菌旋转酶和/或拓扑异构酶IV，并可用于治疗细菌感染。
• GYRASE AND TOPOISOMERASE IV INHIBITORS
  申请人：Le Tiran Arnaud

  公开号：US20120184512A1

  公开（公告）日：2012-07-19

  The present invention relates to a compound of formula (I) or a pharmaceutically acceptable salt thereof wherein X and R are as defined herein. The compounds of formula (I) are useful as gyrase and/or topoisomerase IV inhibitors for treating bacterial infections. The compounds of formula (I) either possess a broad range of anti-bacterial activity and advantageous toxicological properties or are prodrugs of compounds having said activity.

  本发明涉及公式(I)的化合物或其药用盐，其中X和R如本文所定义。公式(I)的化合物可用作治疗细菌感染的旋转酶和/或拓扑异构酶IV抑制剂。公式(I)的化合物具有广泛的抗菌活性和有利的毒理学特性，或者是具有该活性的化合物的前药。
• [EN] COMBINATION THERAPY COMPRISING|1 -ETHYL-3-[5-[2-{1 -HYDROXY-1 -METHYL-ETHYL}PYRIMIDIN-5-YL]-7-(TETRA HYDROFURAN-2-|YL}-1 H-BENZIMIDAZOL-2-YL]UREA AND DERIVATIVES THEREOF TO TREAT MYCOBACTERIUM|DISEASES<br/>[FR] THÉRAPIE COMBINÉE COMPRENANT DE LA 1-ÉTHYL-3[5-[-2-{1-HYDROXY-1-MÉTHYL-ÉTHYL}PYRIMIDIN-5-YL]-7-(TÉTRAHYDROFURAN-2-YL}-1H-BENZIMIDAZOL-2-YL]URÉE ET SES DÉRIVÉS POUR TRAITER DES MALADIES MYCOBACTÉRIENNES
  申请人：VERTEX PHARMA

  公开号：WO2014014845A1

  公开（公告）日：2014-01-23

  The present invention relates to combination therapies comprising a compound of formula (I) or a pharmaceutically acceptable salt thereof wherein X and R are as defined herein. The compounds of formula (I) are useful as gyrase and/or topoisomerase IV inhibitors for treating bacterial infections. The compounds of formula (I) either possess a broad range of anti-bacterial activity and advantageous toxicological properties or are prodrugs of compounds having said activity.

  本发明涉及组合疗法，包括公式(I)化合物或其药学上可接受的盐，其中X和R如本文所定义。公式(I)化合物可用作革兰氏阴性菌和/或拓扑异构酶IV抑制剂，用于治疗细菌感染。公式(I)化合物具有广泛的抗菌活性和优越的毒理学特性，或是具有该活性的化合物的前药。
• [EN] PYRIMIDINE GYRASE AND TOPOISOMERASE IV INHIBITORS<br/>[FR] INHIBITEURS DE PYRIMIDINE GYRASE ET TOPOÏSOMÉRASE IV
  申请人：VERTEX PHARMA

  公开号：WO2012097269A1

  公开（公告）日：2012-07-19

  The present invention relates to a compound of formula (I): or a pharmaceutically acceptable salt thereof wherein X and R are as defined herein. The compounds of formula (I) are useful as gyrase and/or topoisomerase IV inhibitors for treating bacterial infections. The compounds of formula (I) either possess a broad range of anti¬ bacterial activity and advantageous toxicological properties or are prodrugs of compounds having said activity.

  本发明涉及一种公式(I)的化合物或其药学上可接受的盐，其中X和R如本文所定义。公式(I)的化合物对于治疗细菌感染作为陀螺酶和/或拓扑异构酶IV抑制剂是有用的。公式(I)的化合物具有广泛的抗菌活性和优良的毒理学特性，或者是具有该活性的化合物的前药。