2-(4-methoxyphenyl)-2-(3-chloropropyl)-5,5-dimethyl-1,3-dioxane | 56327-36-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 2-(4-methoxyphenyl)-2-(3-chloropropyl)-5,5-dimethyl-1,3-dioxane
• 英文别名: 2-(3-chloro-propyl)-2-(4-methoxy-phenyl)-5,5-dimethyl-[1,3]dioxane；1,3-Dioxane, 2-(3-chloropropyl)-2-(4-methoxyphenyl)-5,5-dimethyl-；2-(3-chloropropyl)-2-(4-methoxyphenyl)-5,5-dimethyl-1,3-dioxane
• CAS: 56327-36-7
• 化学式: C₁₆H₂₃ClO₃
• 分子量: 298.81
• InChiKey: YDBSKUFQAFZOHA-UHFFFAOYSA-N

物化性质

• 熔点：
  54 °C
• 沸点：
  3174 °C
• 密度：
  1.070±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  20
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  27.7
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-(4-methoxyphenyl)-2-(3-chloropropyl)-5,5-dimethyl-1,3-dioxane 、 7-methoxy-2,3,4,5-tetrahydro-1H-benzo[d]azepin-1-ol 在 四丁基碘化铵 、 potassium carbonate 作用下， 以 乙腈 为溶剂， 以79%的产率得到7-methoxy-3-(3-(2-(4-methoxyphenyl)-5,5-dimethyl-1,3-dioxan-2-yl)propyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepin-1-ol
  参考文献：
  名称：

  Design, Synthesis, and Biological Evaluation of 3-Benzazepin-1-ols as NR2B-Selective NMDA Receptor Antagonists

  摘要：

  AbstractCleavage and reconstitution of a bond in the piperidine ring of ifenprodil (1) leads to 7‐methoxy‐2,3,4,5‐tetrahydro‐1H‐3‐benzazepin‐1‐ols, a novel class of NR2B‐selective NMDA receptor antagonists. The secondary amine 7‐methoxy‐2,3,4,5‐tetrahydro‐1H‐3‐benzazepin‐1‐ol (12), which was synthesized in six steps starting from 2‐phenylethylamine 3, represents the central building block for the introduction of several N‐linked residues. A distance of four methylene units between the basic nitrogen atom and the phenyl residue in the side chain results in high NR2B affinity. The 4‐phenylbutyl derivative 13 (WMS‐1405, Ki=5.4 nM) and the conformationally restricted 4‐phenylcyclohexyl derivative 31 (Ki=10 nM) represent the most potent NR2B ligands of this series. Whereas 13 shows excellent selectivity, the 4‐phenylcyclohexyl derivative 31 also interacts with σ1 (Ki=33 nM) and σ2 receptors (Ki=82 nM). In the excitotoxicity assay the phenylbutyl derivative 13 inhibits the glutamate‐induced cytotoxicity with an IC50 value of 360 nM, indicating that 13 is an NMDA antagonist.

  DOI：

  10.1002/cmdc.201000005
• 作为产物：
  描述：

  Γ-氯-4-甲氧基苯丁酮 以309%的产率得到
  参考文献：
  名称：

  LEDNICER D.; EMMERT D. E.; RUDZIK A. D.; GRAHAM B. E., J. MED. CHEM. , 1975, 18, NO 6, 593-599

  摘要：

  DOI：

文献信息

• Butyrophenones as hypotensive agents. Derivatives of 4-aryl-4-(hydroxymethyl)cyclohexylamine
  作者：Daniel Lednicer、D. Edward Emmert、Alan D. Rudzik、Boyd E. Graham

  DOI：10.1021/jm00240a014

  日期：1975.6

  preparation of butyrophenone derivatives of 4-aryl-4-(hydroxymethyl)cyclohex-1-ylamines starting from the corresponding 4-cyano-4-phenylcyclohexan-1-ones is described. Substitution was varied with both rings; both isomers of 4-phenyl-4-(hydroxymethyl)cyclohex-1-ylamine were characterized. Those derivatives which carried p-fluoro substitution on the butyrophenone exhibited hypotensive activity in the rat with

  描述了从相应的4-氰基-4-苯基环己酮-1-酮开始制备4-芳基-4-（羟甲基）环己-1-基胺的丁苯酮衍生物。两个环都有不同的取代基；对4-苯基-4-（羟甲基）环己-1-基胺的两种异构体进行了表征。与缺乏羟甲基的化合物相比，在丁苯酮上进行对氟取代的那些衍生物在大鼠中表现出降压活性，而CNS活性降低。讨论了取代对4-芳基环的影响。
• Conformationally constrained NR2B selective NMDA receptor antagonists derived from ifenprodil: Synthesis and biological evaluation of tetrahydro-3-benzazepine-1,7-diols
  作者：Bastian Tewes、Bastian Frehland、Dirk Schepmann、Kai-Uwe Schmidtke、Thomas Winckler、Bernhard Wünsch

  DOI：10.1016/j.bmc.2010.09.026

  日期：2010.11.15

  NR2B selective NMDA receptor antagonists with tetrahydro-3-benzazepine-1,7-diol scaffold have been designed by formal cleavage and reconstitution of the piperidine ring of the lead compound ifenprodil (1). The secondary amine 10 represents the central building block for the synthesis of more than 25 tetrahydro-3-benzazepin-1-ols. Generally 7-hydroxy derivatives display higher NR2B receptor affinities than the corresponding 7-benzyloxy compounds. A distance of four atoms (five bond lengths) between the basic amino group and the terminal aryl moiety led to highest NR2B affinity. 3-(4-Phenylbutyl)-2,3,4,5- tetrahydro-1H-3-benzazepine-1,7-diol (WMS-1410, 25) represents the most promising NR2B antagonist of this series showing a K-i-value of 14 nM. Compound 25 reveals excellent selectivity over more than 100 further relevant target proteins, antagonizes glutamate induced excitotoxicity (IC50 = 18.4 nM) and is metabolically more stable than ifenprodil. Up to a dose of 100 mg/kg 25 is well tolerated by mice and it shows dose dependent analgesic activity in the late neuropathic pain phase of the formalin assay. (C) 2010 Elsevier Ltd. All rights reserved.
• PROST M.; CROMPHAUT V. VAN; VERSTRAETEN W.; DIRKS M.; TORNAY C.; COLOT M.+, EUR. J. MED. CHEM.-CHIM. THER., 1980, 15, NO 3, 215-222
  作者：PROST M.、 CROMPHAUT V. VAN、 VERSTRAETEN W.、 DIRKS M.、 TORNAY C.、 COLOT M.+

  DOI：——

  日期：——