1-(3,5-dihydroxyphenyl)-1-heptyne | 180989-36-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 酚类
• 英文名称: 1-(3,5-dihydroxyphenyl)-1-heptyne
• 英文别名: 5-Hept-1-ynylbenzene-1,3-diol
• CAS: 180989-36-0
• 化学式: C₁₃H₁₆O₂
• 分子量: 204.269
• InChiKey: PMZXIHCWJOPJOE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  15
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  40.5
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1-(3,5-dihydroxyphenyl)-1-heptyne 在 正丁基锂 、 LiCuCN(imidazolide) 、 三氟化硼乙醚 、 对甲苯磺酸 作用下， 以 乙醚 为溶剂， 反应 5.0h， 生成 (1R,4R,5R)-4-[2,6-Bis-(2-ethoxy-ethoxy)-4-hept-1-ynyl-phenyl]-6,6-dimethyl-bicyclo[3.1.1]heptan-2-one
  参考文献：
  名称：

  不饱和侧链β-11-羟基六氢大麻酚类似物。

  摘要：

  大麻素侧链是大麻素与其受体（CB1和CB2）相互作用的关键药效​​团。为了研究侧链的立体化学要求，我们合成了一系列大麻素，其中围绕C1'-C2'键的旋转被阻止。合成中的关键步骤是向（+）-apoverbenone取代的间苯二酚进行铜酸盐的加成，TMSOTf介导的二氢吡喃环的形成以及β-11-羟甲基的立体定向引入。所有测试的类似物均显示出对受体的纳摩尔亲和力，其中顺式-庚-1-烯侧链对CB1的亲和力最高（Ki = 0.89 nM），并且在CB1和CB2亲和力之间的分离范围最广。母体正庚基-β-11-羟基六氢大麻酚与CB1的结合力最低（Ki = 8。

  DOI：

  10.1021/jm950934b
• 作为产物：
  描述：

  1-(2,2-二溴乙烯基)-3,5-二甲氧基苯 在 六甲基磷酰三胺 、 正丁基锂 、 三溴化硼 作用下， 以 二氯甲烷 为溶剂， 反应 21.5h， 生成 1-(3,5-dihydroxyphenyl)-1-heptyne
  参考文献：
  名称：

  Pharmacophoric Requirements for Cannabinoid Side Chains:  Multiple Bond and C1‘-Substituted Δ⁸-Tetrahydrocannabinols

  摘要：

  Accumulated evidence indicates that within the cannabinoid structure the aliphatic side chain plays a pivotal role in determining cannabimimetic activity. We describe the synthesis and affinities for the CB1 and CB2 receptors of a series of novel Delta(8)-THC analogues in which the side-chain pharmacophores are conformationally more defined than in the parent molecule. No analogue has the side-chain pharmacophore in a fully restricted conformation. However, our design serves to narrow down the scope of options for conformational requirements at the receptor active sites. All the analogues tested showed nanomolar or subnanomolar affinities for the receptors; 2-(6a,7,10,10a-tetrahydro-6,6,9-trimethyl-1-hydroxy-6H-dibenzo[b,d]pyranyl)- 2-hexyl-1,3-dithiolane was found to possess very high affinity for both cannabinoid receptors(CB1, K-i = 0.32 nM; CB2, K-i = 0.52 nM).

  DOI：

  10.1021/jm970277i

文献信息

• Development of agonists, partial agonists and antagonists in the Δ8-Tetrahydrocannabinol series
  作者：Peter J. Crocker、Bijali Saha、William J. Ryan、Jenny L. Wiley、Billy R. Martin、Ruth A. Ross、Roger G. Pertwee、Raj K. Razdan

  DOI：10.1016/s0040-4020(99)00849-2

  日期：1999.12

  sequences were developed (Schemes 1 to 6) for the syntheses of various Δ8-THC analogs with either a rigid acetylenic linkage or a cis-double bond in different positions in the side chain. Various alkyne and cis-ene-Δ8-THC analogs were also synthesized carrying a functional group such as a cyano, isothiocyano, azido, amino, nitro, bromo, hydroxy, fluoro and a methoxy group at the chain terminal. The in

  合成序列被开发用于各种的合成（方案1至6）Δ 8 -THC类似物与任一刚性炔键或CIS在侧链不同的位置-双键。各种炔和顺式-烯Δ 8个-THC类似物还合成携带功能性基团，如氰基，异硫氰基，叠氮基，氨基，硝基，溴，羟基，氟和在链末端为甲氧基。在体外和体内这些独特的类似物的药理学已经提供了若干配位体是部分激动剂或大麻素受体CB1拮抗剂。发现侧链中的2'-位置对于活性是最佳的。
• Unsaturated Side Chain β-11-Hydroxyhexahydrocannabinol Analogs
  作者：Jakob Busch-Petersen、W. Adam Hill、Pusheng Fan、Atmaram Khanolkar、Xuang-Qun Xie、Marcus A. Tius、Alexandros Makriyannis

  DOI：10.1021/jm950934b

  日期：1996.1.1

  The cannabinoid side chain is a key pharmacophore in the interaction of cannabinoids with their receptors (CB1 and CB2). To study the stereochemical requirements of the side chain, we synthesized a series of cannabinoids in which rotation around the C1'-C2' bond is blocked. The key steps in the synthesis were the cuprate addition of a substituted resorcinol to (+)-apoverbenone, the TMSOTf-mediated

  大麻素侧链是大麻素与其受体（CB1和CB2）相互作用的关键药效​​团。为了研究侧链的立体化学要求，我们合成了一系列大麻素，其中围绕C1'-C2'键的旋转被阻止。合成中的关键步骤是向（+）-apoverbenone取代的间苯二酚进行铜酸盐的加成，TMSOTf介导的二氢吡喃环的形成以及β-11-羟甲基的立体定向引入。所有测试的类似物均显示出对受体的纳摩尔亲和力，其中顺式-庚-1-烯侧链对CB1的亲和力最高（Ki = 0.89 nM），并且在CB1和CB2亲和力之间的分离范围最广。母体正庚基-β-11-羟基六氢大麻酚与CB1的结合力最低（Ki = 8。
• Pharmacophoric Requirements for Cannabinoid Side Chains:  Multiple Bond and C1‘-Substituted Δ⁸-Tetrahydrocannabinols
  作者：Demetris P. Papahatjis、Therapia Kourouli、Vasiliki Abadji、Andreas Goutopoulos、Alexandros Makriyannis

  DOI：10.1021/jm970277i

  日期：1998.3.1

  Accumulated evidence indicates that within the cannabinoid structure the aliphatic side chain plays a pivotal role in determining cannabimimetic activity. We describe the synthesis and affinities for the CB1 and CB2 receptors of a series of novel Delta(8)-THC analogues in which the side-chain pharmacophores are conformationally more defined than in the parent molecule. No analogue has the side-chain pharmacophore in a fully restricted conformation. However, our design serves to narrow down the scope of options for conformational requirements at the receptor active sites. All the analogues tested showed nanomolar or subnanomolar affinities for the receptors; 2-(6a,7,10,10a-tetrahydro-6,6,9-trimethyl-1-hydroxy-6H-dibenzo[b,d]pyranyl)- 2-hexyl-1,3-dithiolane was found to possess very high affinity for both cannabinoid receptors(CB1, K-i = 0.32 nM; CB2, K-i = 0.52 nM).