1-(3,5-二甲氧基苯基)环丙烷-1-甲醛 | 339094-28-9

• 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)环丙烷-1-甲醛
• 英文名称: 1-(3,5-dimethoxyphenyl)cyclopropanecarboxaldehyde
• 英文别名: 1-(3,5-Dimethoxyphenyl)cyclopropane-1-carbaldehyde；1-(3,5-dimethoxyphenyl)cyclopropane-1-carbaldehyde
• CAS: 339094-28-9
• 化学式: C₁₂H₁₄O₃
• 分子量: 206.241
• InChiKey: MDFFCKPYGFTVBR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  15
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  35.5
• 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)环丙烷-1-甲醛 在 hexamethyldisilazide 作用下， 以 四氢呋喃 、 正己烷 为溶剂， 反应 2.75h， 生成 5-[1-[(1Z)-1-hexenyl]cyclopropyl]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-(3,5-dimethoxyphenyl)cyclopropanecarbonitrile 在 二异丁基氢化铝 作用下， 以 二氯甲烷 为溶剂， 以85 %的产率得到1-(3,5-二甲氧基苯基)环丙烷-1-甲醛
  参考文献：
  名称：

  发现用于治疗抑郁和焦虑的 CB2 和 5-HT1A 受体双重激动剂

  摘要：

  与 CB 1 R 激动剂相比，大麻素 CB 2 R 激动剂由于其非精神活性性质，作为精神疾病的潜在新疗法而受到广泛关注。在本研究中，我们采用分子对接设计并合成了23种大麻二酚（CBD）衍生物，目的是发现有效的CB 2 R激动剂而不是CB 2 R拮抗剂或反向激动剂。构效关系 (SAR) 研究强调了 C-3' 位点的酰胺基团和 C-4' 位点的环烷基对于 CB 2 R 活化的至关重要性。有趣的是，三种 CBD 衍生物，即2o 、 6g和6h ，对 CB 2受体表现出显着的部分激动活性，这与 CBD 的反向激动特性相反。其中， 2o作为 CB 2 R 和 5-HT 1A R 双重激动剂，尽管对 CB 1 R 具有一些不需要的拮抗剂活性。它表现出显着的 CB 2 R 部分激动作用，同时保持 5-HT 1A R 激动水平和CB 1 R 拮抗活性与 CBD 类似。药代动力学实验证实2o具有良好的药代动力学特性。行为研究进一步表明，

  DOI：

  10.1016/j.ejmech.2023.116048

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。
• 一类间苯二酚化合物及其制备方法以及在神经系统疾病中的应用
  申请人：中国科学院上海药物研究所

  公开号：CN114507153A

  公开（公告）日：2022-05-17

  本发明涉及一类间苯二酚化合物及其制备方法以及在神经系统疾病中的应用。具体地，本发明提供了一种式(I)表示的间苯二酚类化合物、其对映异构体、非对映异构体、外消旋体及其混合物，以及其药学上可接受的无机或有机盐、结晶水合物及溶剂合物。本发明还提供了所述化合物的制备方法以及其在制备预防和/或治疗中枢神经系统疾病的药物中的应用。
• Novel 1′,1′-chain substituted Δ8-tetrahydrocannabinols
  作者：Demetris P. Papahatjis、Spyros P. Nikas、Thanos Andreou、Alexandros Makriyannis

  DOI：10.1016/s0960-894x(02)00785-0

  日期：2002.12

  1',1'-Cyclopropyl side chain substituents enhance the affinities of Delta(8)-tetrahydrocannabinol and respective cannabidiol analogues for the CB1 and CB2 cannabinoid receptors. The results support the hypothesis for a subsite within CB1 and CB2 binding domain at the level of the benzylic side chain carbon in the tetrahydrocannabinol and cannabidiol series. Efficient procedures for the synthesis of 1',1'-cyclopropyl analogues are described. (C) 2002 Elsevier Science Ltd. All rights reserved.
• 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.
• Discovery of a CB2 and 5-HT1A receptor dual agonist for the treatment of depression and anxiety
  作者：Wenjiao Yang、Xudong Gong、Haiguo Sun、Chunhui Wu、Jin Suo、Jing Ji、Xiangrui Jiang、Jingshan Shen、Yang He、Haji Akber Aisa

  DOI：10.1016/j.ejmech.2023.116048

  日期：2024.2

  Cannabinoid CB2R agonists have gained considerable attention as potential novel therapies for psychiatric disorders due to their non-psychoactive nature, in contrast to CB1R agonists. In this study, we employed molecular docking to design and synthesize 23 derivatives of cannabidiol (CBD) with the aim of discovering potent CB2R agonists rather than CB2R antagonists or inverse agonists. Structure-activity

  与 CB 1 R 激动剂相比，大麻素 CB 2 R 激动剂由于其非精神活性性质，作为精神疾病的潜在新疗法而受到广泛关注。在本研究中，我们采用分子对接设计并合成了23种大麻二酚（CBD）衍生物，目的是发现有效的CB 2 R激动剂而不是CB 2 R拮抗剂或反向激动剂。构效关系 (SAR) 研究强调了 C-3' 位点的酰胺基团和 C-4' 位点的环烷基对于 CB 2 R 活化的至关重要性。有趣的是，三种 CBD 衍生物，即2o 、 6g和6h ，对 CB 2受体表现出显着的部分激动活性，这与 CBD 的反向激动特性相反。其中， 2o作为 CB 2 R 和 5-HT 1A R 双重激动剂，尽管对 CB 1 R 具有一些不需要的拮抗剂活性。它表现出显着的 CB 2 R 部分激动作用，同时保持 5-HT 1A R 激动水平和CB 1 R 拮抗活性与 CBD 类似。药代动力学实验证实2o具有良好的药代动力学特性。行为研究进一步表明，