1-(1-bromo-2-fluoroethyl)-4-methylbenzene | 834155-48-5

• 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: 1-(1-bromo-2-fluoroethyl)-4-methylbenzene
• 英文别名: 1-(1-Bromo-2-fluoroethyl)-4-methylbenzene
• CAS: 834155-48-5
• 化学式: C₉H₁₀BrF
• 分子量: 217.081
• InChiKey: KXNFXXVIJPTDPM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  11
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  0
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  (S)-N¹-(1-methoxy-3-(p-tolyl)propan-2-yl)benzene-1,2-diamine 、 1-(1-bromo-2-fluoroethyl)-4-methylbenzene 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 N¹-(2-fluoro-1-(p-tolyl)ethyl)-N²-((S)-1-methoxy-3-(p-tolyl)propan-2-yl)benzene-1,2-diamine 、 N¹-(2-fluoro-1-(p-tolyl)ethyl)-N²-((S)-1-methoxy-3-(p-tolyl)propan-2-yl)benzene-1,2-diamine
  参考文献：
  名称：

  基于芳烃或吡啶稠合 1,3-二氢-2H-咪唑-2-亚胺的新型食欲素受体激动剂

  摘要：

  设计了一类结构新颖的苯并或吡啶并稠合 1,3-二氢-2-咪唑-2-亚胺，并在肌醇磷酸盐积累测定中进行了评估，用于 G 信号传导，以测量 2 型食欲素受体 (OXR) 的激动活性。这些化合物是用容易获得的起始材料通过 4-9 个步骤合成的。苄基中心含有立体甲基或环丙基取代基以及正确配置的烷基醚、烷氧基烷基醚、氰基烷基醚或 α-羟基乙酰胺基取代的同质苄基侧链的类似物被认为是 OXR 偶联 G 信号传导的最有效激活剂。我们的结果还表明，苯甲基和同型苯甲基立体中心的激动活性都是立体特异性的。我们发现，含有立体异构苯甲基的甲氧基乙氧基取代的吡啶并稠合二氢咪唑亚胺类似物是最有效的激动剂，在该测定中记录了 339 nM 的 EC 值和 96% 的最大响应 (E)。体内药代动力学分析表明几种类似物具有良好的脑暴露效果。我们的综合结果为与当前化学类型不同的结构新颖的一类食欲素受体激动剂提供了重要信息。

  DOI：

  10.1016/j.bmcl.2024.129624
• 作为产物：
  描述：

  Alpha-甲基苯乙烯 在 N-溴代丁二酰亚胺(NBS) 、 triethylamine tris(hydrogen fluoride) 作用下， 以 二氯甲烷 为溶剂， 生成 1-(2-溴-1-氟乙基)-4-甲基苯 、 1-(1-bromo-2-fluoroethyl)-4-methylbenzene
  参考文献：
  名称：

  Fluorinated Phenylcyclopropylamines. 2. Effects of Aromatic Ring Substitution and of Absolute Configuration on Inhibition of Microbial Tyramine Oxidase

  摘要：

  A series of para-substituted diastereopure cis- and trans-2-fluoro-2-arylcyclopropylamines were synthesized and these were investigated as inhibitors of microbial tyramine oxidase from Arthrobacter sp. All compounds were shown to be competitive inhibitors of this enzyme. The nature of the para-substituents in the more potent trans-isomer (cis-relationship between fluorine and the amino group) of 2-fluoro-2-arylcyclopropylamine influenced the inhibitory potency in a consistent fashion. Thus, electron-withdrawing groups (F, Cl) slightly decreased the activity, while the methyl group (+ I substituent) increased the activity by a factor of ca. 7 compared to trans-2-fluoro-2-phenylcyclopropylamine and by a factor of 90 compared to tranylcypromine. Activity also was strongly dependent on the absolute configuration. The (1S,2S)-enantiomer of 2-fluoro-2-phenylcyclopropylamine was an excellent inhibitor of tyramine oxidase whereas the (1R,2R)-enantiomer was essentially devoid of activity.

  DOI：

  10.1021/jm049957t

文献信息

• Fluorinated Phenylcyclopropylamines. 2. Effects of Aromatic Ring Substitution and of Absolute Configuration on Inhibition of Microbial Tyramine Oxidase
  作者：Thomas C. Rosen、Shinichi Yoshida、Roland Fröhlich、Kenneth L. Kirk、Günter Haufe

  DOI：10.1021/jm049957t

  日期：2004.11.1

  A series of para-substituted diastereopure cis- and trans-2-fluoro-2-arylcyclopropylamines were synthesized and these were investigated as inhibitors of microbial tyramine oxidase from Arthrobacter sp. All compounds were shown to be competitive inhibitors of this enzyme. The nature of the para-substituents in the more potent trans-isomer (cis-relationship between fluorine and the amino group) of 2-fluoro-2-arylcyclopropylamine influenced the inhibitory potency in a consistent fashion. Thus, electron-withdrawing groups (F, Cl) slightly decreased the activity, while the methyl group (+ I substituent) increased the activity by a factor of ca. 7 compared to trans-2-fluoro-2-phenylcyclopropylamine and by a factor of 90 compared to tranylcypromine. Activity also was strongly dependent on the absolute configuration. The (1S,2S)-enantiomer of 2-fluoro-2-phenylcyclopropylamine was an excellent inhibitor of tyramine oxidase whereas the (1R,2R)-enantiomer was essentially devoid of activity.
• Novel orexin receptor agonists based on arene- or pyridine-fused 1,3-dihydro-2H-imidazole-2-imines
  作者：Wentian Wang、Alok Ranjan、Wei Zhang、Qiren Liang、Karen S. MacMillan、Karen Chapman、Xiaoyu Wang、Preethi Chandrasekaran、Noelle S. Williams、Daniel M. Rosenbaum、Jef K. De Brabander

  DOI：10.1016/j.bmcl.2024.129624

  日期：2024.2

  in an inositol phosphate accumulation assay for G signaling to measure agonistic activation of the orexin receptor type 2 (OXR). These compounds were synthesized in 4–9 steps overall from readily available starting materials. Analogs that contain a stereogenic methyl or cyclopropyl substituent at the benzylic center, and a correctly configured alkyl ether, alkoxyalkyl ether, cyanoalkyl ether, or α-hydroxyacetamido

  设计了一类结构新颖的苯并或吡啶并稠合 1,3-二氢-2-咪唑-2-亚胺，并在肌醇磷酸盐积累测定中进行了评估，用于 G 信号传导，以测量 2 型食欲素受体 (OXR) 的激动活性。这些化合物是用容易获得的起始材料通过 4-9 个步骤合成的。苄基中心含有立体甲基或环丙基取代基以及正确配置的烷基醚、烷氧基烷基醚、氰基烷基醚或 α-羟基乙酰胺基取代的同质苄基侧链的类似物被认为是 OXR 偶联 G 信号传导的最有效激活剂。我们的结果还表明，苯甲基和同型苯甲基立体中心的激动活性都是立体特异性的。我们发现，含有立体异构苯甲基的甲氧基乙氧基取代的吡啶并稠合二氢咪唑亚胺类似物是最有效的激动剂，在该测定中记录了 339 nM 的 EC 值和 96% 的最大响应 (E)。体内药代动力学分析表明几种类似物具有良好的脑暴露效果。我们的综合结果为与当前化学类型不同的结构新颖的一类食欲素受体激动剂提供了重要信息。