1-((2-bromoethoxy)(phenyl)methyl)-4-chlorobenzene | 92425-35-9

• 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-((2-bromoethoxy)(phenyl)methyl)-4-chlorobenzene
• 英文别名: 1-[2-Bromoethoxy(phenyl)methyl]-4-chlorobenzene
• CAS: 92425-35-9
• 化学式: C₁₅H₁₄BrClO
• 分子量: 325.633
• InChiKey: IJJMFCFMKJYVCK-UHFFFAOYSA-N

物化性质

• 沸点：
  152-153 °C(Press: 0.05 Torr)
• 密度：
  1.391±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  18
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  9.2
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  1-((2-bromoethoxy)(phenyl)methyl)-4-chlorobenzene 在 lithium hydroxide 、 potassium carbonate 作用下， 以 甲醇 、 乙腈 为溶剂， 反应 79.0h， 生成 1-<2-<(4-chlorophenyl)phenylmethoxy>ethyl>-3-piperidinecarboxylic acid
  参考文献：
  名称：

  Structure-activity studies on benzhydrol-containing nipecotic acid and guvacine derivatives as potent, orally-active inhibitors of GABA uptake

  摘要：

  The introduction of lipophilic groups onto the ring nitrogen of nipecotic acid and guvacine, two known GABA uptake inhibitors, afforded potent, orally-active anticonvulsant drugs. A series of compounds is reported which explores the structure-activity relationships (SAR) in this series. Among the areas explored: side-chain SAR (aromatic-, heterocyclic-, and tricyclic-containing side chains) and modifications to the tetrahydropyridine ring. The benzhydrol ether-containing side chains afforded the most potent compounds with several exhibiting in vitro IC50 values for GABA uptake of <1 muM (including 5, Table 1; 37, 43, Table IV; and 44, Table V). Compound 44 was selected for extensive evaluation and subsequently progressed to Phase 1 clinical trials with severe adverse effects seen after single dose administration to humans.

  DOI：

  10.1021/jm00100a032
• 作为产物：
  描述：

  4-氯二苯甲酮 在 sodium tetrahydroborate 、 硫酸 作用下， 以 异丙醇 、 甲苯 为溶剂， 反应 21.0h， 生成 1-((2-bromoethoxy)(phenyl)methyl)-4-chlorobenzene
  参考文献：
  名称：

  Structure-activity studies on benzhydrol-containing nipecotic acid and guvacine derivatives as potent, orally-active inhibitors of GABA uptake

  摘要：

  The introduction of lipophilic groups onto the ring nitrogen of nipecotic acid and guvacine, two known GABA uptake inhibitors, afforded potent, orally-active anticonvulsant drugs. A series of compounds is reported which explores the structure-activity relationships (SAR) in this series. Among the areas explored: side-chain SAR (aromatic-, heterocyclic-, and tricyclic-containing side chains) and modifications to the tetrahydropyridine ring. The benzhydrol ether-containing side chains afforded the most potent compounds with several exhibiting in vitro IC50 values for GABA uptake of <1 muM (including 5, Table 1; 37, 43, Table IV; and 44, Table V). Compound 44 was selected for extensive evaluation and subsequently progressed to Phase 1 clinical trials with severe adverse effects seen after single dose administration to humans.

  DOI：

  10.1021/jm00100a032

文献信息

• Synthesis of azolylethyl benzhydryl ethers, analogs of diphenhydramine
  作者：M. L. Burdeinyi、S. V. Popkov、M. V. Kharchevnikova

  DOI：10.1007/s11172-009-0118-z

  日期：2009.5

  Alternative approaches to the preparation of azolylethyl benzhydryl ethers have been studied. It was shown that the reaction of diphenylmethyl halide with 2-(azol-1-yl)ethanol in the presence of triethylamine is the optimum way. An efficient method for the synthesis of 2-(imidazol-1-yl)ethanol using phase-transfer catalysis has been developed.

  已经研究了制备唑基乙基二苯甲基醚的替代方法。结果表明，在三乙胺存在下，二苯甲基卤化物与2-(唑-1-基)乙醇反应是最佳的反应方式。已开发出一种使用相转移催化合成 2-(咪唑-1-基) 乙醇的有效方法。
• Synthesis and dopamine transporter binding affinities of 3α-Benzyl-8-(diarylmethoxyethyl)-8-azabicyclo[3.2.1]octanes
  作者：Amy L Bradley、Sari Izenwasser、Dean Wade、Cheryl Klein-Stevens、Naijue Zhu、Mark L Trudell

  DOI：10.1016/s0960-894x(02)00464-x

  日期：2002.9

  A series of 3alpha-benzyl-8-(diarylmethoxyethyl)-8-azabicyclo[3.2.1]octanes was synthesized and the binding affinities of the compounds were determined at the dopamine transporter. The unsubstituted analogue 7b (K-i = 98 nM) was the most potent compound of the series with binding affinity three-times greater than cocaine and only 5-fold less than GBR-12909. The structure-activity data for 7a-f suggests that these compounds may be binding at the dopamine transporter in a similar fashion to GBR 12909. (C) 2002 Elsevier Science Ltd. All rights reserved.
• Synthesis, biological evaluation, and molecular docking investigation of benzhydrol- and indole-based dual PPAR-γ/FFAR1 agonists
  作者：Khaled M. Darwish、Ismail Salama、Samia Mostafa、Mohamed S. Gomaa、El-Sayed Khafagy、Mohamed A. Helal

  DOI：10.1016/j.bmcl.2018.03.051

  日期：2018.5

  Type-2 diabetes mellitus is a progressive cluster of metabolic disorders, representing a global public health burden affecting more than 366 million people worldwide. We recently reported the discovery of three series of novel agents showing balanced activity on two metabolic receptors, peroxisome proliferator activated receptor-gamma (PPAR-gamma) and free fatty acid receptor 1 (FFAR1), also known as GPCR40. Our designing strategy relied on linking the thiazolidinedione head with known GPCR privilege structures. To further investigate this concept, two new scaffolds, the benzhydrol- and indole-based chemotypes, were introduced here in. Our optimization campaign resulted in three compounds; 15a, 15c, and 15d, with affinities in the low micromolar range on both targets. In vivo study of selected test compounds, revealed that 15c possesses a significant anti-hyperglycemic and anti-hyperlipidemic activities superior to rosiglitazone in fat-fed animal models. Molecular docking analysis was conducted to explain the binding modes of both series. These compounds could lead to the development of the unique antidiabetic agent acting as insulin sensitizer as well as insulin secretagogue. (C) 2018 Elsevier Ltd. All rights reserved.
• WO2023/47107
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  公开号：——

  公开（公告）日：——