1-(3,5-二甲氧基苯基)环戊烷-1-腈 | 339094-26-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 1-(3,5-二甲氧基苯基)环戊烷-1-腈
• 英文名称: 1-(3,5-dimethoxyphenyl)cyclopentanecarbonitrile
• 英文别名: 1-(3,5-dimethoxyphenyl)cyclopentane-1-carbonitrile
• CAS: 339094-26-7
• 化学式: C₁₄H₁₇NO₂
• 分子量: 231.294
• InChiKey: XOKSFPBKNABGTF-UHFFFAOYSA-N

物化性质

• 沸点：
  402.8±45.0 °C(Predicted)
• 密度：
  1.10±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  42.2
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-(3,5-二甲氧基苯基)环戊烷-1-腈 在 palladium on activated charcoal 氢气 、 hexamethyldisilazide 、 三溴化硼 、 二异丁基氢化铝 作用下， 以 四氢呋喃 、 二氯甲烷 、 乙酸乙酯 为溶剂， 反应 78.75h， 生成 5-(1-heptylcyclopentyl)resorcinol
  参考文献：
  名称：

  C1‘-Cycloalkyl Side Chain Pharmacophore in Tetrahydrocannabinols

  摘要：

  In earlier work we have provided evidence for the presence of a subsite within the CB1 and CB2 cannabinoid receptor binding domains of classical cannabinoids. This putative subsite corresponds to substituents on the C1'-position of the C3-alkyl side chain, a key pharmacophoric feature in this class of compounds. We have now refined this work through the synthesis of additional C1'-cycloalkyl compounds using newly developed approaches. Our findings indicate that the C1'-cyclopropyl and C1'-cyclopentyl groups are optimal pharmacophores for both receptors while the C1'-cyclobutyl group interacts optimally with CB1 but not with CB2. The C1'-cyclohexyl analogs have reduced affinities for both CB1 and CB2. However, these affinities are significantly improved with the introduction of a C2'-C3' cis double bond that modifies the available conformational space within the side chain and allows for a better accommodation of a six-membered ring within the side chain subsite. Our SAR results are highlighted by molecular modeling of key analogs.

  DOI：

  10.1021/jm070121a
• 作为产物：
  描述：

  1,4-二溴丁烷 、 3,5-二甲氧基苯基乙腈 在 双(三甲基硅烷基)氨基钾 作用下， 以 四氢呋喃 为溶剂， 反应 0.13h， 以88%的产率得到1-(3,5-二甲氧基苯基)环戊烷-1-腈
  参考文献：
  名称：

  大麻素侧链的药理学要求。在C1'处探测大麻素受体亚位点。

  摘要：

  我们实验室的早期工作为CB1和CB2大麻素受体结合域内存在一个亚位点提供了证据，该位点对应于经典大麻素苄基侧链位置的取代基。现在已经通过合成一系列带有C1'-环取代基的（-）-Delta（8）-四氢大麻酚类似物来探索该亚位点的存在和立体化学特征。在本文所述的化合物中，具有C1'-二硫杂环戊烷（1c），C1'-二氧戊环（2d）和环戊基（2a）取代基的化合物表现出对CB1和CB2的最高亲和力。我们使用分子建模方法更好地定义了假定亚位点的立体化学极限。体外药理测试发现1c是有效的CB1激动剂。

  DOI：

  10.1021/jm020558c

文献信息

• A New Ring-Forming Methodology for the Synthesis of Conformationally Constrained Bioactive Molecules
  作者：Demetris P. Papahatjis、Spyros Nikas、Andrew Tsotinis、Margarita Vlachou、Alexandros Makriyannis

  DOI：10.1246/cl.2001.192

  日期：2001.3

  A new, general, one pot method for introducing carbocyclic rings alpha to a nitrile moiety is described. Treatment of readily available arylacetonitriles with potassium bis(trimethylsilyl)amide and subsequent alkylation with α, ω-dibromo or dichloroalkanes in tetrahydrofuran under anhydrous conditions at 0 °C produces cycloalkyl adducts in good yields and short reaction times.

  描述了一种新的通用一锅法，用于在腈基前引入碳环。将 readily available 的芳基乙腈与氨基钾双(trimethylsilyl)处理，随后在无水条件下于0 °C的四氢呋喃中与α,ω-二溴或二氯烷烃进行烷基化，可以在短反应时间内以良好的产率生成环烷基附加物。
• Novel Functionalized Cannabinoid Receptor Probes: Development of Exceptionally Potent Agonists
  作者：Shan Jiang、Christos Iliopoulos-Tsoutsouvas、Fei Tong、Christina A. Brust、Catherine M. Keenan、Jimit Girish Raghav、Tian Hua、Simiao Wu、Jo-Hao Ho、Yiran Wu、Travis W. Grim、Nikolai Zvonok、Ganesh A. Thakur、Zhi-Jie Liu、Keith A. Sharkey、Laura M. Bohn、Spyros P. Nikas、Alexandros Makriyannis

  DOI：10.1021/acs.jmedchem.0c02053

  日期：2021.4.8
• Structural modifications of the cannabinoid side chain towards C3-aryl and 1′,1′-cycloalkyl-1′-cyano cannabinoids
  作者：Demetris P. Papahatjis、Victoria R. Nahmias、Thanos Andreou、Pusheng Fan、Alexandros Makriyannis

  DOI：10.1016/j.bmcl.2005.12.026

  日期：2006.3

  The compounds reported in this study are Delta(8)-THC analogues in which the C3 five-carbon linear side chain of Delta(8)-THC was replaced with aryl and 1',1'-cycloalkyl substituents. Of the compounds described here analogues 2d (CB1, K-i = 11.7 nM. CB2, K-i = 9.39 nM) and 2f (CB1, K-i = 8.26 nM. CB2, K-i = 3.86 nM) exhibited enhanced binding affinities for CB1 and CB2, exceeding that of Delta(8)-THC. Efficient procedures for the synthesis of these novel cannabinoid analogues are described. (C) 2006 Elsevier Ltd. All rights reserved.
• Pharmacophoric Requirements for the Cannabinoid Side Chain. Probing the Cannabinoid Receptor Subsite at C1‘
  作者：Demetris P. Papahatjis、Spyros P. Nikas、Therapia Kourouli、Ravi Chari、Wei Xu、Roger G. Pertwee、Alexandros Makriyannis

  DOI：10.1021/jm020558c

  日期：2003.7.1

  laboratories has provided evidence for the existence of a subsite within the CB1 and CB2 cannabinoid receptor binding domain corresponding to substituents at the benzylic side chain position of classical cannabinoids. The existence and stereochemical features of this subsite have now been probed through the synthesis of a novel series of (-)-Delta(8)-tetrahydrocannabinol analogues bearing C1'-ring substituents

  我们实验室的早期工作为CB1和CB2大麻素受体结合域内存在一个亚位点提供了证据，该位点对应于经典大麻素苄基侧链位置的取代基。现在已经通过合成一系列带有C1'-环取代基的（-）-Delta（8）-四氢大麻酚类似物来探索该亚位点的存在和立体化学特征。在本文所述的化合物中，具有C1'-二硫杂环戊烷（1c），C1'-二氧戊环（2d）和环戊基（2a）取代基的化合物表现出对CB1和CB2的最高亲和力。我们使用分子建模方法更好地定义了假定亚位点的立体化学极限。体外药理测试发现1c是有效的CB1激动剂。
• C1‘-Cycloalkyl Side Chain Pharmacophore in Tetrahydrocannabinols
  作者：Demetris P. Papahatjis、Victoria R. Nahmias、Spyros P. Nikas、Thanos Andreou、Shakiru O. Alapafuja、Andrew Tsotinis、Jianxin Guo、Pusheng Fan、Alexandros Makriyannis

  DOI：10.1021/jm070121a

  日期：2007.8.1

  In earlier work we have provided evidence for the presence of a subsite within the CB1 and CB2 cannabinoid receptor binding domains of classical cannabinoids. This putative subsite corresponds to substituents on the C1'-position of the C3-alkyl side chain, a key pharmacophoric feature in this class of compounds. We have now refined this work through the synthesis of additional C1'-cycloalkyl compounds using newly developed approaches. Our findings indicate that the C1'-cyclopropyl and C1'-cyclopentyl groups are optimal pharmacophores for both receptors while the C1'-cyclobutyl group interacts optimally with CB1 but not with CB2. The C1'-cyclohexyl analogs have reduced affinities for both CB1 and CB2. However, these affinities are significantly improved with the introduction of a C2'-C3' cis double bond that modifies the available conformational space within the side chain and allows for a better accommodation of a six-membered ring within the side chain subsite. Our SAR results are highlighted by molecular modeling of key analogs.