1-[(3-甲基-5-异噁唑)甲基]哌嗪 | 173850-53-8

• 分子结构分类: 有机化合物 - 有机氮化合物
• 中文名称: 1-[(3-甲基-5-异噁唑)甲基]哌嗪
• 英文名称: 3-methyl-5-(N-piperazinomethyl) isoxazole
• 英文别名: 3-Methyl-5-(piperazin-1-ylmethyl)-1,2-oxazole
• CAS: 173850-53-8
• 化学式: C₉H₁₅N₃O
• mdl: MFCD08444202
• 分子量: 181.238
• InChiKey: IICSMQOSSHSZLK-UHFFFAOYSA-N

物化性质

• 沸点：
  298.9±35.0 °C(Predicted)
• 密度：
  1.104±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0
• 重原子数：
  13
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.666
• 拓扑面积：
  41.3
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (E)-3-(4-chloro-2-((5-methyl-2H-tetraazol-2-yl)methyl)phenyl)propaneenoic acid 、 1-[(3-甲基-5-异噁唑)甲基]哌嗪 在 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 生成 3-[4-Chloro-2-[(5-methyltetrazol-2-yl)methyl]phenyl]-1-[4-[(3-methyl-1,2-oxazol-5-yl)methyl]piperazin-1-yl]prop-2-en-1-one
  参考文献：
  名称：

  紫杉醇抑制剂的开发：一系列四唑肉桂酸酯

  摘要：

  已从高通量筛选结果1a中开发了一系列自分泌运动抑制因子（ATX），它显示了与已知催化部位抑制剂的另一种结合方式。在hERG通道上的选择性和微粒体清除率取决于化合物的亲脂性，这通过降低clogD来优化，同时保持了高亲和力ATX抑制。如药代动力学-药效学（PK / PD）实验所示，化合物15a表现出良好的口服暴露以及体内LPA形成的浓度依赖性抑制。

  DOI：

  10.1016/j.bmcl.2020.127663
• 作为产物：
  描述：

  3-甲基-5-异噁唑羧酸甲酯 在 dimethyl sulfide borane 作用下， 以 四氢呋喃 为溶剂， 反应 6.0h， 生成 1-[(3-甲基-5-异噁唑)甲基]哌嗪
  参考文献：
  名称：

  Regioisomeric 3-, 4- and 5-aminomethyl isoxazoles: synthesis and muscarinic activity

  摘要：

  A series of 3-, 4- and 5-aminomethyl isoxazoles and isoxazoles with one or two additional methyl groups at the heterocycle were synthesized in order to investigate the structural requirements, ie heterocyclic moiety, regiochemistry and length of an aminoalkyl unit, for muscarinic activity. This was assayed on isolated rabbit vas deferens (M(1) receptor subtype) and isolated guinea-pig atrium (M(2) receptor subtype) and ileum (M(3) receptor subtype). The isoxazoles tested are one to three orders of magnitude less active than furane or oxadiazole derivatives, having similar structural characteristics except for the heterocycle. Thus, the differences in molecular point charges and charge distribution contribute to the muscarinic activity of these compounds more than small differences in molecular shape and conformational energies.

  DOI：

  10.1016/0223-5234(96)88303-6

文献信息

• Regioisomeric 3-, 4- and 5-aminomethyl isoxazoles: synthesis and muscarinic activity
  作者：G Dannhardt、W Kiefer、G Lambrecht、S Laufer、E Mutschler、J Schweiger、H.G. Striegel

  DOI：10.1016/0223-5234(96)88303-6

  日期：1995.1

  A series of 3-, 4- and 5-aminomethyl isoxazoles and isoxazoles with one or two additional methyl groups at the heterocycle were synthesized in order to investigate the structural requirements, ie heterocyclic moiety, regiochemistry and length of an aminoalkyl unit, for muscarinic activity. This was assayed on isolated rabbit vas deferens (M(1) receptor subtype) and isolated guinea-pig atrium (M(2) receptor subtype) and ileum (M(3) receptor subtype). The isoxazoles tested are one to three orders of magnitude less active than furane or oxadiazole derivatives, having similar structural characteristics except for the heterocycle. Thus, the differences in molecular point charges and charge distribution contribute to the muscarinic activity of these compounds more than small differences in molecular shape and conformational energies.
• Development of autotaxin inhibitors: A series of tetrazole cinnamides
  作者：Christopher G. Thomson、Darren Le Grand、Mark Dowling、David Beattie、Lucy Elphick、Michael Faller、Mark Freeman、Elizabeth Hardaker、Victoria Head、Rene Hemmig、Johan Hill、Andrew Lister、David Pascoe、Sebastien Rieffel、Binesh Shrestha、Oliver Steward、Florence Zink

  DOI：10.1016/j.bmcl.2020.127663

  日期：2021.1

  A series of inhibitors of Autotaxin (ATX) have been developed from a high throughput screening hit, 1a, which shows an alternative binding mode to known catalytic site inhibitors. Selectivity over the hERG channel and microsomal clearance were dependent on the lipophilicity of the compounds, and this was optimised by reduction of clogD whilst maintaining high affinity ATX inhibition. Compound 15a shows

  已从高通量筛选结果1a中开发了一系列自分泌运动抑制因子（ATX），它显示了与已知催化部位抑制剂的另一种结合方式。在hERG通道上的选择性和微粒体清除率取决于化合物的亲脂性，这通过降低clogD来优化，同时保持了高亲和力ATX抑制。如药代动力学-药效学（PK / PD）实验所示，化合物15a表现出良好的口服暴露以及体内LPA形成的浓度依赖性抑制。