1-(3,5-dimethoxyphenyl)cyclobutanecarboxaldehyde | 339094-29-0

• 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-(3,5-dimethoxyphenyl)cyclobutanecarboxaldehyde
• 英文别名: 1-(3,5-Dimethoxyphenyl)cyclobutanecarbaldehyde；1-(3,5-dimethoxyphenyl)cyclobutane-1-carbaldehyde
• CAS: 339094-29-0
• 化学式: C₁₃H₁₆O₃
• 分子量: 220.268
• InChiKey: TVPWIGWYBHBFBP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  16
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.46
• 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-dimethoxyphenyl)cyclobutanecarboxaldehyde 在 palladium on activated charcoal 氢气 、 hexamethyldisilazide 、 三溴化硼 作用下， 以 四氢呋喃 、 二氯甲烷 、 乙酸乙酯 为溶剂， 反应 0.75h， 生成 5-(1-hexylcyclobutyl)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：

  3,5-二甲氧基苯基乙腈 在 双(三甲基硅烷基)氨基钾 、 二异丁基氢化铝 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 生成 1-(3,5-dimethoxyphenyl)cyclobutanecarboxaldehyde
  参考文献：
  名称：

  A New Ring-Forming Methodology for the Synthesis of Conformationally Constrained Bioactive Molecules

  摘要：

  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。

  DOI：

  10.1246/cl.2001.192

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 Bicyclic Cannabinoids
  申请人：Makriyannis Alexandros

  公开号：US20070135388A1

  公开（公告）日：2007-06-14

  Bicyclic-cannabinoids and methods of preparation and use are presented. These compounds, when administered in a therapeutically effective amount to an individual or animal, results in a sufficiently high level of that compound in the individual or animal to cause a physiological response. The physiological response may be useful to treat a number of physiological conditions.

  本文介绍了双环大麻素及其制备和使用方法。当以治疗有效量的这些化合物给个体或动物注射时，会在个体或动物体内产生足够高的该化合物水平，从而引起生理反应。这种生理反应可能对治疗多种生理状况有用。
• Novel 1′,1′-Chain Substituted Hexahydrocannabinols: 9β-Hydroxy-3-(1-hexyl-cyclobut-1-yl)-hexahydrocannabinol (AM2389) a Highly Potent Cannabinoid Receptor 1 (CB1) Agonist
  作者：Spyros P. Nikas、Shakiru O. Alapafuja、Ioannis Papanastasiou、Carol A. Paronis、Vidyanand G. Shukla、Demetris P. Papahatjis、Anna L. Bowman、Aneetha Halikhedkar、Xiuwen Han、Alexandros Makriyannis

  DOI：10.1021/jm100641g

  日期：2010.10.14

  In pursuit of a more detailed understanding of the structural requirements for the key side chain cannabinoid pharmacophore, we have extended our SA R to cover a variety of conformationally modified side chains within the 9-keto and 9-hydroxyl tricyclic structures. OF the compounds described here. those with a seven-atom long side chain substituted with a cyclopentyl ring at Cl' position have very high affinities For both CB1 and CB2 (0.97 nM < K-1 < 5.25 nM), with no preference for either of the two receptors. However, presence of the smaller cyclobutyl group at the Cl' position leads to an optimal affinity and selectivity interaction with CB1. Thus, two of the Cl'-cyclobutyl analogues, namely. (6a R.10aR R)-3-(1-hexyl-cyclobut-1-y1)-6,6a,7,8, 10,10a-hexahydro-1-hydroxy-6,6-dimethyl-9H-dibenzo-[b,d]pyran-9-one and (6aR,9R, 10aR)-3-(1-hexyl-cyclobut-1-yl)-6a,7,8,9,10, 10a-hexahydro-6.6-dimethyl-6H-dibenzo[b,d]pyran-1,9 diol (7e-beta, AM2389), exhibited remarkably high affinities (0.84 and 0.16 nM respectively) and significant selectivities (16- and 26-fold, respectively) for CB1. Compound 7e-beta was found to exhibit exceptionally high in vitro and in vivo potency with a relatively long duration of action.
• US7446229B2
  申请人：——

  公开号：US7446229B2

  公开（公告）日：2008-11-04
• 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.