(6aR,10aR)-1-fluoro-3-heptyl-6,6,9-trimethyl-6a,7,10,10a-tetrahydrobenzo[c]chromene

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡喃
• 英文名称: (6aR,10aR)-1-fluoro-3-heptyl-6,6,9-trimethyl-6a,7,10,10a-tetrahydrobenzo[c]chromene
• 化学式: C₂₃H₃₃FO
• 分子量: 344.513
• InChiKey: UCNQJJFXPQTDLC-RTBURBONSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.3
• 重原子数：
  25
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.65
• 拓扑面积：
  9.2
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  1,3-二甲氧基-5-氟苯 在 palladium on activated charcoal 、 对甲苯磺酸 吡啶 、 三氟甲磺酸酐 、 氢气 、 三溴化硼 作用下， 以 乙醇 、 二氯甲烷 、 苯 为溶剂， -78.0~80.0 ℃ 、101.33 kPa 条件下， 反应 6.0h， 生成 (6aR,10aR)-1-fluoro-3-heptyl-6,6,9-trimethyl-6a,7,10,10a-tetrahydrobenzo[c]chromene
  参考文献：
  名称：

  The role of fluorine substitution in the structure–activity relationships (SAR) of classical cannabinoids

  摘要：

  A facile synthesis of 1-fluoro-1-deoxy-Delta(8)-THC analogs with side chains seven carbons in length, in the alkane/ene/yneseries (6, 5, and 4), was achieved from 1-fluoro-3,5-dimethoxybenzene (1). In vitro studies show that substitution by a fluorine has a significant detrimental effect on CB1 binding which is supported by in vivo testing. The implications of these results on the SAR of classical cannabinoids are discussed. (c) 2007 Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmcl.2007.01.006

文献信息

• Assessment of structural commonality between tetrahydrocannabinol and anandamide
  作者：Billy R Martin、Renee G Jefferson、Ramona Winckler、Jenny L Wiley、Brian F Thomas、Peter J Crocker、William Williams、Raj K Razdan

  DOI：10.1016/s0014-2999(01)01527-8

  日期：2002.1

  the phenolic ring of tetrahydrocannnabinol were altered. In order to examine the alignment of the phenolic hydroxyl of tetrahydrocannnabinol with the hydroxyl group of anandamide, 1-fluoro-1-deoxy-tetrahydrocannnabinol analogs were prepared. These analogs had low affinity for the CB(1) cannabinoid receptor and were considerably less potent than tetrahydrocannnabinol in producing pharmacological effects

  为了进一步在四氢大麻酚和芳烷酰胺之间进行结构比较，改变了四氢大麻酚的酚环的C1和C3处的取代基。为了检查四氢大麻酚的酚羟基与an烷酰胺的羟基的比对，制备了1-氟-1-脱氧四氢大麻酚类似物。这些类似物对CB（1）大麻素受体的亲和力低，并且在小鼠中产生药理作用的效力远低于四氢大麻酚。这些结果表明这两个氧部分不重叠。另外，氟基团只能接受氢键这一事实表明，四氢大麻酚C1位置的酚氧为电子提供氢键结合，而不是羟基的氢与受体相互作用。此外，用氟取代C1处的羟基导致类似物对CB（2）的亲和力高于CB（1）大麻素受体，从而突显了这两种受体亚型的结合特性的根本差异。
• The role of fluorine substitution in the structure–activity relationships (SAR) of classical cannabinoids
  作者：Peter J. Crocker、Anu Mahadevan、Jenny L. Wiley、Billy R. Martin、Raj K. Razdan

  DOI：10.1016/j.bmcl.2007.01.006

  日期：2007.3

  A facile synthesis of 1-fluoro-1-deoxy-Delta(8)-THC analogs with side chains seven carbons in length, in the alkane/ene/yneseries (6, 5, and 4), was achieved from 1-fluoro-3,5-dimethoxybenzene (1). In vitro studies show that substitution by a fluorine has a significant detrimental effect on CB1 binding which is supported by in vivo testing. The implications of these results on the SAR of classical cannabinoids are discussed. (c) 2007 Published by Elsevier Ltd.