4-(4-溴苯基)四氢-2H-吡喃 | 811828-76-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 4-(4-溴苯基)四氢-2H-吡喃
• 中文别名: 4-(4-溴苯基)四氢吡喃
• 英文名称: 4-(4-bromophenyl)tetrahydro-2H-pyran
• 英文别名: 4-(4-Bromophenyl)tetrahydropyran；4-(4-bromophenyl)oxane
• CAS: 811828-76-9
• 化学式: C₁₁H₁₃BrO
• 分子量: 241.128
• InChiKey: JTRPUGBQABMPMD-UHFFFAOYSA-N

物化性质

• 沸点：
  301.9±30.0 °C(Predicted)
• 密度：
  1.355±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  13
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  9.2
• 氢给体数：
  0
• 氢受体数：
  1

安全信息

• 海关编码：
  2932999099
• 危险性防范说明：
  P280,P305+P351+P338
• 危险性描述：
  H302

反应信息

• 作为反应物：
  描述：

  4-(4-溴苯基)四氢-2H-吡喃 在 1,1'-双(二苯膦基)二茂铁二氯化钯(II)二氯甲烷复合物 、 potassium acetate 、 sodium carbonate 作用下， 以 水 、 乙腈 为溶剂， 反应 1.0h， 生成 8-(3-chloro-5-(4-(tetrahydro-2H-pyran-4-yl)phenyl)pyridin-4-yl)-2,8-diazaspiro[4.5]decan-1-one
  参考文献：
  名称：

  Discovery of Potent, Orally Bioavailable, Small-Molecule Inhibitors of WNT Signaling from a Cell-Based Pathway Screen

  摘要：

  WNT signaling is frequently deregulated in malignancy, particularly in colon cancer, and plays a key role in the generation and maintenance of cancer stem cells. We report the discovery and optimization of a 3,4,5-trisubstituted pyridine 9 using a high-throughput cell-based reporter assay of WNT pathway activity. We demonstrate a twisted conformation about the pyridine-piperidine bond of 9 by small-molecule X-ray crystallography. Medicinal chemistry optimization to maintain this twisted conformation, cognisant of physicochemical properties likely to maintain good cell permeability, led to 74 (CCT251545), a potent small-molecule inhibitor of WNT signaling with good oral pharmacokinetics. We demonstrate inhibition of WNT pathway activity in a solid human tumor xenograft model with evidence for tumor growth inhibition following oral dosing. This work provides a successful example of hypothesis-driven medicinal chemistry optimization from a singleton hit against a cell-based pathway assay without knowledge of the biochemical target.

  DOI：

  10.1021/jm501436m
• 作为产物：
  描述：

  1,4-二溴苯 在 三乙基硅烷 、 正丁基锂 、 三氟乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 4.5h， 生成 4-(4-溴苯基)四氢-2H-吡喃
  参考文献：
  名称：

  Discovery of Potent, Orally Bioavailable, Small-Molecule Inhibitors of WNT Signaling from a Cell-Based Pathway Screen

  摘要：

  WNT signaling is frequently deregulated in malignancy, particularly in colon cancer, and plays a key role in the generation and maintenance of cancer stem cells. We report the discovery and optimization of a 3,4,5-trisubstituted pyridine 9 using a high-throughput cell-based reporter assay of WNT pathway activity. We demonstrate a twisted conformation about the pyridine-piperidine bond of 9 by small-molecule X-ray crystallography. Medicinal chemistry optimization to maintain this twisted conformation, cognisant of physicochemical properties likely to maintain good cell permeability, led to 74 (CCT251545), a potent small-molecule inhibitor of WNT signaling with good oral pharmacokinetics. We demonstrate inhibition of WNT pathway activity in a solid human tumor xenograft model with evidence for tumor growth inhibition following oral dosing. This work provides a successful example of hypothesis-driven medicinal chemistry optimization from a singleton hit against a cell-based pathway assay without knowledge of the biochemical target.

  DOI：

  10.1021/jm501436m

文献信息

• SUBSTITUTED PYRIDOPYRAZINES AS NOVEL SYK INHIBITORS
  申请人：Su Wei-Guo

  公开号：US20140121200A1

  公开（公告）日：2014-05-01

  Provided are pyridopyrazine compounds of formula (1), pharmaceutical compositions thereof and methods of use therefore, wherein R 1 , R 2 , R 3 , R 4 and m are as defined in the specification.

  提供了式（1）的吡啶吡嗪化合物，以及其药物组合物和使用方法，其中R1、R2、R3、R4和m如规范中所定义。
• [EN] 6,7,8,9-TETRAHYDRO-5H-PYRIDO[2,3-d]AZEPINE DOPAMINE D3 LIGANDS<br/>[FR] LIGANDS 6,7,8,9-TÉTRAHYDRO-5H-PYRIDO[2,3-D]AZÉPINE DU RÉCEPTEUR D3 DE LA DOPAMINE
  申请人：PFIZER

  公开号：WO2017122116A1

  公开（公告）日：2017-07-20

  The present invention provides compounds of Formula (I): and pharmaceutically acceptable salts thereof wherein the variables R1, R2, R3, R4, R5, a and A are as defined herein; processes for the preparation of; intermediates used in the preparation of; and compositions containing such compounds or salts, and their uses for treating D3-mediated (or D3-associated) disorders including, e.g., substance addiction, substance abuse, schizophrenia (e.g., its cognitive symptoms), cognitive impairment (e.g., cognitive impairment associated with schizophrenia, AD or PD), Parkinson's disease, mania, anxiety, impulse control disorders, sexual disorders and depression.

  本发明提供了Formula (I)的化合物及其药学上可接受的盐，其中变量R1、R2、R3、R4、R5、a和A如本文所定义；制备方法；制备中使用的中间体；以及含有这种化合物或盐的组合物，以及它们用于治疗D3介导的（或与D3相关的）疾病，包括物质成瘾、物质滥用、精神分裂症（例如其认知症状）、认知障碍（例如与精神分裂症、阿尔茨海默病或帕金森病相关的认知障碍）、帕金森病、狂躁症、焦虑、冲动控制障碍、性功能障碍和抑郁症等疾病的用途。
• A Versatile Route to Unstable Diazo Compounds via Oxadiazolines and their Use in Aryl-Alkyl Cross-Coupling Reactions
  作者：Andreas Greb、Jian-Siang Poh、Stephanie Greed、Claudio Battilocchio、Patrick Pasau、David C. Blakemore、Steven V. Ley

  DOI：10.1002/anie.201710445

  日期：2017.12.22

  Coupling of readily available boronic acids and diazo compounds has emerged recently as a powerful metal-free carbon-carbon bond forming method. However, the difficulty in forming the unstable diazo compound partner in a mild fashion has hitherto limited their general use and the scope of the transformation. Here, we report the application of oxadiazolines as precursors for the generation of an unstable

  作为一种有效的无金属碳-碳键形成方法，最近出现了易于获得的硼酸和重氮化合物的偶联。然而，迄今为止，以温和的方式形成不稳定的重氮化合物伴侣的困难限制了它们的一般用途和转化范围。在这里，我们报道了恶二唑啉作为前体的应用，它使用流式紫外光解法生成不稳定的重氮化合物家族，并首次用于不同的原去硼和氧化C（sp2）-C（sp3）交叉偶联过程中，具有出色的功能组容忍度。
• [EN] GLUCOSYLCERAMIDE SYNTHASE INHIBITORS FOR THE TREATMENT OF DISEASES<br/>[FR] INHIBITEURS DE LA GLUCOSYLCÉRAMIDE SYNTHASE POUR LE TRAITEMENT DE MALADIES
  申请人：BIOMARIN PHARM INC

  公开号：WO2015042397A1

  公开（公告）日：2015-03-26

  Described herein are compounds of Formula I, methods of making such compounds, pharmaceutical compositions and medicaments containing such compounds, and methods of using such compounds to treat or prevent diseases or conditions associated with the enzyme glucosylceramide synthase (GCS).

  本文描述了一种I式化合物，制备这种化合物的方法，含有这种化合物的药物组合物和药物，以及使用这种化合物治疗或预防与葡萄糖酰胺合成酶（GCS）相关的疾病或症状的方法。
• [EN] SUBSTITUTED PYRIDOPYRAZINES AS NOVEL SYK INHIBITORS<br/>[FR] PYRIDOPYRAZINES SUBSTITUÉES EN TANT QUE NOUVEAUX INHIBITEURS DE SYK
  申请人：HUTCHISON MEDIPHARMA LTD

  公开号：WO2012167733A1

  公开（公告）日：2012-12-13

  Provided are pyridopyrazine compounds of formula (I), pharmaceutical compositions thereof and methods of use therefore, wherein R1, R2, R3, R4 and m are as defined in the specification.

  提供了式（I）的吡啶吡嗪化合物，其药物组合物以及使用方法，其中R1、R2、R3、R4和m如规范中所定义。