N-(4-methoxybenzyl)isoxazol-3-amine | 1269530-62-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: N-(4-methoxybenzyl)isoxazol-3-amine
• 英文别名: N-[(4-methoxyphenyl)methyl]-1,2-oxazol-3-amine
• CAS: 1269530-62-2
• 化学式: C₁₁H₁₂N₂O₂
• 分子量: 204.228
• InChiKey: XNCXJZIYQYJNKD-UHFFFAOYSA-N

物化性质

• 沸点：
  367.6±22.0 °C(Predicted)
• 密度：
  1.204±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  15
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  47.3
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-(4-methoxybenzyl)isoxazol-3-amine 在 1,1'-双(二苯膦基)二茂铁二氯化钯(II)二氯甲烷复合物 、 sodium hexamethyldisilazane 、 sodium carbonate 作用下， 以 四氢呋喃 、 1,4-二氧六环 为溶剂， 反应 1.25h， 生成 3-chloro-1-(2-chloro-3'-fluoro-5-methoxy-[1,1'-biphenyl]-4-yl)-N-(isoxazol-3-yl)-N-(4-methoxybenzyl)-isoquinoline-6-sulfonamide
  参考文献：
  名称：

  Sulfonamides as Selective Na_V1.7 Inhibitors: Optimizing Potency and Pharmacokinetics While Mitigating Metabolic Liabilities

  摘要：

  Several reports have recently emerged regarding the identification of heteroarylsulfonamides as Na(V)1.7 inhibitors that demonstrate high levels of selectivity over other Na-V isoforms. The optimization of a series of internal Na(V)1.7 leads that address a number of metabolic liabilities including bioactivation, PXR activation, as well as CYP3A4 induction and inhibition led to the identification of potent and selective inhibitors that demonstrated favorable pharmacokinetic profiles and were devoid of the aforementioned liabilities. The key to achieving this within a series prone to transporter-mediated clearance was the identification of a small range of optimal cLogD values and the discovery of subtle PXR SAR that was not lipophilicity dependent. This enabled the identification of compound 20, which was advanced into a target engagement pharmacodynamic model where it exhibited robust reversal of histamine-induced scratching bouts in mice.

  DOI：

  10.1021/acs.jmedchem.6b01851
• 作为产物：
  描述：

  3-氨基异恶唑 、 4-甲氧基苯甲醛 在 溶剂黄146 、 molybdenum(VI) oxychloride 、 苯硅烷 作用下， 以 甲醇 、 水 为溶剂， 反应 16.25h， 以75%的产率得到N-(4-methoxybenzyl)isoxazol-3-amine
  参考文献：
  名称：

  CYCLOPROPYL DIHYDROQUINOLINE SULFONAMIDE COMPOUNDS

  摘要：

  本发明提供了一种式（I）的化合物：其对映体、异构体、异构体、混合物或其药学上可接受的盐，该化合物抑制电压门控钠通道，特别是NaV1.7。这些化合物对治疗与钠通道活性相关的疾病如疼痛障碍、咳嗽和瘙痒具有用处。还提供了含有本发明化合物的药物组合物。还进一步提供了所述式（I）化合物的对映选择性制备以及其中间体。

  公开号：

  US20210387977A1

文献信息

• [EN] ALKYL DIHYDROQUINOLINE SULFONAMIDE COMPOUNDS<br/>[FR] COMPOSÉS SULFONAMIDES DE DIHYDROQUINOLINE D'ALKYLE
  申请人：AMGEN INC

  公开号：WO2017106871A1

  公开（公告）日：2017-06-22

  The present invention provides compounds of Formula (I), and pharmaceutically acceptable salts thereof, that are inhibitors of voltage-gated sodium channels, in particular Nav1.7. The compounds are useful for the treatment of diseases associated with the activity of sodium channels such as pain disorders, cough, and itch. Also provided are pharmaceutical compositions containing compounds of the present invention.

  本发明提供了式（I）的化合物及其药学上可接受的盐，这些化合物是钠通道的抑制剂，特别是Nav1.7。这些化合物对于治疗与钠通道活性相关的疾病，如疼痛障碍、咳嗽和瘙痒，是有用的。还提供了含有本发明化合物的药物组合物。
• [EN] PYRIDINE SULFONAMIDES<br/>[FR] SULFONAMIDES DE PYRIDINE
  申请人：AMGEN INC

  公开号：WO2018017896A1

  公开（公告）日：2018-01-25

  The present invention provides compounds of Formula (I), as defined in the specification, or pharmaceutically acceptable salts thereof, that are inhibitors of voltage-gated sodium channels, in particular Nav 1.7. The compounds are useful for the treatment of diseases treatable by inhibition of sodium channels such as pain disorders, cough, or itch. Also provided are pharmaceutical compositions containing compounds of the present invention.

  本发明提供了如规范中定义的Formula (I)的化合物，或其药用可接受的盐，这些化合物是电压门控钠通道的抑制剂，特别是Nav 1.7。这些化合物对于治疗可通过抑制钠通道治疗的疾病如疼痛障碍、咳嗽或瘙痒是有用的。还提供了含有本发明化合物的药物组合物。
• Bicyclic sulfonamide compounds as sodium channel inhibitors
  申请人：AMGEN INC.

  公开号：US09212182B2

  公开（公告）日：2015-12-15

  The present invention provides compounds of Formula I, and pharmaceutically acceptable salts thereof, that are inhibitors of voltage-gated sodium channels, in particular Nav1.7. The compounds are useful for the treatment of diseases associated with the activity of sodium channels such as pain disorders and itch. Also provided are pharmaceutical compositions containing compounds of the present invention.

  本发明提供了式I的化合物及其药学上可接受的盐，这些化合物是钠通道的抑制剂，特别是Nav1.7。这些化合物对于治疗与钠通道活性相关的疾病，如疼痛障碍和瘙痒，是有用的。还提供了含有本发明化合物的药物组合物。
• CYCLOBUTYL DIHYDROQUINOLINE SULFONAMIDE COMPOUNDS
  申请人：AMGEN INC.

  公开号：US20210387978A1

  公开（公告）日：2021-12-16

  The present invention provides a cyclobutyl dihydroquinoline sulfonamide compound of Formula (I), an enantiomer, diastereoisomer, atropisomer thereof, a mixture thereof, or a pharmaceutically acceptable salt thereof, that inhibits voltage-gated sodium channels, in particular Nav1.7. The compounds are useful for the treatment of diseases associated with the activity of sodium channels such as pain disorders, cough, and itch. Also provided are pharmaceutical compositions containing the compounds of the present invention. Also further provided is an atropi-selective preparation of said compounds of Formula (I), and intermediate thereof.

  本发明提供了一种公式（I）的环丁基二氢喹啉磺胺化合物，其对电压门控钠通道，特别是Nav1.7具有抑制作用的对映体、顺反异构体、对映异构体、混合物或其药学上可接受的盐。这些化合物对治疗与钠通道活性相关的疾病如疼痛障碍、咳嗽和瘙痒等方面具有用处。还提供了含有本发明化合物的药物组合物。此外，还提供了一种选择性对映异构体的制备方法，以及该公式（I）化合物及其中间体。
• CYCLOPROPYL DIHYDROQUINOLINE SULFONAMIDE COMPOUNDS
  申请人：AMGEN INC.

  公开号：US20210387977A1

  公开（公告）日：2021-12-16

  The present invention provides a compound of Formula (I): an enantiomer, diastereoisomer, atropisomer thereof, a mixture thereof, or a pharmaceutically acceptable salt thereof, that inhibits voltage-gated sodium channels, in particular NaV1.7. The compounds are useful for the treatment of diseases associated with the activity of sodium channels such as pain disorders, cough, and itch. Also provided are pharmaceutical compositions containing the compounds of the present invention. Also further provided is an atropi-selective preparation of said compounds of Formula (I), and intermediate thereof.

  本发明提供了一种式（I）的化合物：其对映体、异构体、异构体、混合物或其药学上可接受的盐，该化合物抑制电压门控钠通道，特别是NaV1.7。这些化合物对治疗与钠通道活性相关的疾病如疼痛障碍、咳嗽和瘙痒具有用处。还提供了含有本发明化合物的药物组合物。还进一步提供了所述式（I）化合物的对映选择性制备以及其中间体。