ethyl 1-(4-bromophenyl)-4-methyl-5-phenyl-1H-pyrazole-3-carboxylate | 1284281-28-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: ethyl 1-(4-bromophenyl)-4-methyl-5-phenyl-1H-pyrazole-3-carboxylate
• 英文别名: Ethyl 1-(4-bromophenyl)-4-methyl-5-phenylpyrazole-3-carboxylate
• CAS: 1284281-28-2
• 化学式: C₁₉H₁₇BrN₂O₂
• 分子量: 385.26
• InChiKey: APCGESLGDKOUQC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  24
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.16
• 拓扑面积：
  44.1
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  ethyl 1-(4-bromophenyl)-4-methyl-5-phenyl-1H-pyrazole-3-carboxylate 在 草酰氯 、 N,N-二甲基甲酰胺 、 lithium hydroxide 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 为溶剂， 生成
  参考文献：
  名称：

  N-(4-Cyanotetrahydro-2H-pyran-4-yl) and N-(1-Cyanocyclohexyl) Derivatives of 1,5-Diarylpyrazole-3-carboxamides Showing High Affinity for 18 kDa Translocator Protein and/or Cannabinoid Receptors

  摘要：

  In order to develop improved radioligands for imaging brain CB(1) receptors with positron emission tomography (PET) based on rimonabant (5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-N-(piperidin-1-yl)-1H-pyrazole-3-carboxamide, 1), we synthesized compounds 9a-s in which the N-piperidinyl ring was replaced with a 4-(4-cyanotetrahydro-2H-pyranyl) or 1-cyanocyclohexyl ring. Such changes were expected to be almost isosteric with 1, confer greater metabolic resistance, and in the case of the 4-(4-cyanotetrahydro-2H-pyranyl) compounds, substantially reduce lipophilicity. One derivative, 1-(2-bromophenyl)-N-(1-cyanocyclohexyl)-5-(4-methoxyphenyl)-4-methylpyrazole-3-carboxamide (9n), showed high affinity (K(i) = 15.7 nM) and selectivity for binding to CB(1) receptors. The corresponding 4-(4-cyanotetrahydro-2H-pyranyl) derivative (9m) also showed quite high affinity for CB(1) receptors (K(i) = 62 nM) but was found to have even higher affinity (K(i) = 29 nM) for the structurally unrelated 18 kDa translocator protein (TSPO). Some other minor structural changes among 9a-s were also found to switch binding selectivity from CB(1) receptors to TSPO or vice versa. These unexpected findings and their implications for the development of selective ligands or PET radioligands for CB(1) receptors or TSPO are discussed in relation to current pharmacophore models of CB(1) receptor and TSPO binding sites.

  DOI：

  10.1021/jm2000536
• 作为产物：
  描述：

  苯丙酮 在 四氯化钛 、 magnesium sulfate 、 N,N-二异丙基乙胺 作用下， 以 乙醇 、 甲苯 为溶剂， 反应 16.0h， 生成 ethyl 1-(4-bromophenyl)-4-methyl-5-phenyl-1H-pyrazole-3-carboxylate
  参考文献：
  名称：

  N-(4-Cyanotetrahydro-2H-pyran-4-yl) and N-(1-Cyanocyclohexyl) Derivatives of 1,5-Diarylpyrazole-3-carboxamides Showing High Affinity for 18 kDa Translocator Protein and/or Cannabinoid Receptors

  摘要：

  In order to develop improved radioligands for imaging brain CB(1) receptors with positron emission tomography (PET) based on rimonabant (5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-N-(piperidin-1-yl)-1H-pyrazole-3-carboxamide, 1), we synthesized compounds 9a-s in which the N-piperidinyl ring was replaced with a 4-(4-cyanotetrahydro-2H-pyranyl) or 1-cyanocyclohexyl ring. Such changes were expected to be almost isosteric with 1, confer greater metabolic resistance, and in the case of the 4-(4-cyanotetrahydro-2H-pyranyl) compounds, substantially reduce lipophilicity. One derivative, 1-(2-bromophenyl)-N-(1-cyanocyclohexyl)-5-(4-methoxyphenyl)-4-methylpyrazole-3-carboxamide (9n), showed high affinity (K(i) = 15.7 nM) and selectivity for binding to CB(1) receptors. The corresponding 4-(4-cyanotetrahydro-2H-pyranyl) derivative (9m) also showed quite high affinity for CB(1) receptors (K(i) = 62 nM) but was found to have even higher affinity (K(i) = 29 nM) for the structurally unrelated 18 kDa translocator protein (TSPO). Some other minor structural changes among 9a-s were also found to switch binding selectivity from CB(1) receptors to TSPO or vice versa. These unexpected findings and their implications for the development of selective ligands or PET radioligands for CB(1) receptors or TSPO are discussed in relation to current pharmacophore models of CB(1) receptor and TSPO binding sites.

  DOI：

  10.1021/jm2000536

文献信息

• Palladium-catalyzed late-stage mono-aroylation of the fully substituted pyrazoles via aromatic C–H bond activation
  作者：Miao-Miao Chen、Ling-Yan Shao、Li-Jun Lun、Yu-Liang Wu、Xiao-Pan Fu、Ya-Fei Ji

  DOI：10.1016/j.cclet.2018.09.022

  日期：2019.3

  5-diaryl-1H-pyrazole-3-carboxylates has been developed via direct and exclusive mono-Csp2 H bond activation with broad substrate scope and good functional group tolerance. A dual-core dimeric palladacycle is confirmed by X-ray single crystal crystallography, and probably serves as an active species in the catalytic cycle.

  摘要通过直接和排他的单-Csp2 H键活化，具有宽的底物范围和良好的官能团耐受性，开发了钯催化的4-甲基-1,5-二芳基-1H-吡唑-3-羧酸酯的后期芳基化反应。X射线单晶晶体学证实了双核二聚体帕拉达环，并且可能在催化循环中用作活性物质。