1-chloro-3-[2-(4-tert-butylphenyl)-5,5-dimethyl-1,3-dioxan-2-yl]propane | 1229622-27-8

• 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-chloro-3-[2-(4-tert-butylphenyl)-5,5-dimethyl-1,3-dioxan-2-yl]propane
• 英文别名: 2-(4-Tert-butylphenyl)-2-(3-chloropropyl)-5,5-dimethyl-1,3-dioxane
• CAS: 1229622-27-8
• 化学式: C₁₉H₂₉ClO₂
• 分子量: 324.891
• InChiKey: RGEUNGJNALBCGJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  22
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.68
• 拓扑面积：
  18.5
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1-chloro-3-[2-(4-tert-butylphenyl)-5,5-dimethyl-1,3-dioxan-2-yl]propane 、 7-benzyloxy-2,3,4,5-tetrahydro-1H-3-benzazepine-1-ol 在 四丁基碘化铵 、 potassium carbonate 作用下， 以 乙腈 为溶剂， 反应 72.0h， 以74%的产率得到7-(benzyloxy)-3-{3-[2-(4-tert-butylphenyl)-5,5-dimethyl-1,3-dioxan-2-yl]propyl}-2,3,4,5-tetrahydro-1H-3-benzazepine-1-ol
  参考文献：
  名称：

  Conformationally constrained NR2B selective NMDA receptor antagonists derived from ifenprodil: Synthesis and biological evaluation of tetrahydro-3-benzazepine-1,7-diols

  摘要：

  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.

  DOI：

  10.1016/j.bmc.2010.09.026
• 作为产物：
  描述：

  2,2-二甲基-1,3-丙二醇 、 4'-叔丁基-4-氯丁酰苯 在 对甲苯磺酸 作用下， 以 甲苯 为溶剂， 反应 4.0h， 生成 1-chloro-3-[2-(4-tert-butylphenyl)-5,5-dimethyl-1,3-dioxan-2-yl]propane
  参考文献：
  名称：

  [EN] NR2B SELECTIVE NMDA-RECEPTOR ANTAGONISTS FOR TREATMENT OF IMMUNE-MEDIATED INFLAMMATORY DISEASES
  [FR] ANTAGONISTES DU RÉCEPTEUR NMDA SÉLECTIFS DE NR2B POUR LE TRAITEMENT DE MALADIES INFLAMMATOIRES À MÉDIATION IMMUNITAIRE

  摘要：

  本发明提供了治疗免疫介导性炎症性疾病的新手段和方法。

  公开号：

  WO2017036880A1

文献信息

• [EN] NR2B-SELECTIVE NMDA-RECEPTOR ANTAGONISTS<br/>[FR] ANTAGONISTES DES RÉCEPTEURS NMDA SÉLECTIFS DU SITE NR2B
  申请人：UNIV MUENSTER WILHELMS

  公开号：WO2010122134A1

  公开（公告）日：2010-10-28

  The present invention relates to compounds according to general formula (I) and pharmaceutical compositions comprising compounds according to general formula (I).

  本发明涉及符合一般式（I）的化合物以及包含符合一般式（I）的化合物的药物组合物。
• Phenol—Benzoxazolone bioisosteres: Synthesis and biological evaluation of tricyclic GluN2B‐selective <i>N</i> ‐methyl‐ <scp>d</scp> ‐aspartate receptor antagonists
  作者：Alexander Markus、Julian A. Schreiber、Gunnar Goerges、Bastian Frehland、Guiscard Seebohm、Dirk Schepmann、Bernhard Wünsch

  DOI：10.1002/ardp.202200147

  日期：2022.9

  reduced with NaBH4 to yield the aminoalcohol 20, which was alkylated or reductively alkylated to form tertiary amines 21f–21r. In the last step, the allyl protective group of 21 was removed with RhCl3 and HCl to obtain oxazolones 22. In receptor binding studies using [3H]ifenprodil as radioligand ketone, 22m showed the highest GluN2B affinity (Ki = 88 nM). However, a reduced affinity toward GluN2B subunit-containing

  三环四氢恶唑并[4,5 - h ]-[3]苯并氮杂-9-醇22被设计为四氢-3-苯并氮杂-1,7-二醇的苯酚生物等排体。该合成的关键特征是在杂环 N 原子上引入了三氟甲基磺酰基和烯丙基保护基团。开发了两种方法来将三氟甲酰基保护的酮16转化为带有各种 N-取代基的三环醇21 。根据第一种方法，通过K 2 CO 3去除三氟甲亚磺酸盐。在用 NaBH(OAc) 3选择性还原17的亚氨基部分后，得到氨基酮18，其被还原烷基化和还原。根据第二种方法，亚胺酮17的亚胺和酮均被 NaBH 4还原，得到氨基醇20，其被烷基化或还原烷基化形成叔胺21f-21r。最后一步用RhCl 3和HCl除去21的烯丙基保护基，得到恶唑酮22。在使用 [ 3 H]ifenprodil 作为放射性配体酮的受体结合研究中， 22m显示出最高的 GluN2B 亲和力（K i  = 88 nM）。然而，对含 GluN2B 亚基的N的亲和力降低与生物等排的
• NR2B-selective NMDA-receptor antagonists
  申请人：Westfälische Wilhelms-Universität Münster

  公开号：EP2246331A1

  公开（公告）日：2010-11-03

  The present invention relates to NMDA antagonists that target the NR2B subunit according to general formula (I) and pharmaceutical compositions comprising compounds according to general formula (I).

  本发明涉及根据通式（I）靶向 NR2B 亚基的 NMDA 拮抗剂和包含根据通式（I）化合物的药物组合物。
• Design, Synthesis, and Biological Evaluation of 3-Benzazepin-1-ols as NR2B-Selective NMDA Receptor Antagonists
  作者：Bastian Tewes、Bastian Frehland、Dirk Schepmann、Kai-Uwe Schmidtke、Thomas Winckler、Bernhard Wünsch

  DOI：10.1002/cmdc.201000005

  日期：2010.5.3

  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.
• NR2B SELECTIVE NMDA-RECEPTOR ANTAGONISTS FOR TREATMENT OF IMMUNE-MEDIATED INFLAMMATORY DISEASES
  申请人：WESTFALISCHE WILHELMS-UNIVERSITAT MUNSTER

  公开号：US20180250308A1

  公开（公告）日：2018-09-06

  The present invention provides novel means and methods for treatment auf immunemediated inflammatory diseases.