ethyl (E)-4-hydroxy-3-methyl-6-oxo-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthalenyl)-2-hexenoate | 156910-46-2

• 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: ethyl (E)-4-hydroxy-3-methyl-6-oxo-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthalenyl)-2-hexenoate
• 英文别名: Ethyl (E)-4-hydroxy-3-methyl-6-oxo-6-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthalenyl)-2-hexenoate；ethyl (E)-4-hydroxy-3-methyl-6-oxo-6-(3,5,5,8,8-pentamethyl-6,7-dihydronaphthalen-2-yl)hex-2-enoate
• CAS: 156910-46-2
• 化学式: C₂₄H₃₄O₄
• 分子量: 386.532
• InChiKey: SMKWWCOQDSREFS-FOWTUZBSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.5
• 重原子数：
  28
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  63.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  ethyl (E)-4-hydroxy-3-methyl-6-oxo-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthalenyl)-2-hexenoate 在 1,2-双(三甲基硅氧基)乙烷 、 对甲苯磺酸 、 甲基磺酰氯 、 三乙胺 作用下， 以 四氢呋喃 、 苯 为溶剂， 反应 5.5h， 生成 2-(4-carbethoxy-3-methyl-(1E,3E)-butadienyl)-2-(5,6,7,8-tetrahydro-3,5,5,8,8-pentamethyl-2-naphthalenyl)-1,3-dioxolane
  参考文献：
  名称：

  Conformational Effects on Retinoid Receptor Selectivity. 2. Effects of Retinoid Bridging Group on Retinoid X Receptor Activity and Selectivity

  摘要：

  The natural retinoid 9-cis-retinoic acid is an activating ligand for both the retinoic acid receptors (RARs) and the retinoid X receptors (RXRs), which are members of the retinoid/thyroid hormone/steroid hormone family of nuclear receptor proteins that activate gene transcription through specific response elements. The pharmacophoric groups necessary to confer RXR selectivity were established by evaluating the ability of 21 conformationally restricted retinoids to activate, the TREpal retinoic acid receptor response element for gene transcription in the presence of one of the three RAR subtypes or RXR alpha. In contrast to those retinoids selective for the RARs, these RXR-selective retinoids have one less atom in the bridge linking the hydrophobic and carboxylic acid termini of the retinoid skeleton. Therefore, a one-carbon bridge replaces the 19-methyl group and SE-double bond of S-cis-retinoic acid and is further functionalized by inclusion in an isopropylidene group, a dioxolane ring, or a cyclopropane ring for optimal RXR alpha activity and selectivity. In addition, the beta-geranylidene and 20-methyl-(11E,13E)-dienoic acid groups of g-cis-retinoic acid are replaced by a 5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2 naphthalenyl ring and a 4-carboxylphenyl ring, respectively, for optimal activation and selectivity. RXR alpha; selectivity is reduced on replacement of the 4-carboxylphenyl group by a 2-carboxyl-5-thienyl group or the S-cis-retinoic acid methylpentadienoic acid terminus.

  DOI：

  10.1021/jm00017a021
• 作为产物：
  描述：

  1,1,4,4,6-五甲基-1,2,3,4-四氢化萘 在 正丁基锂 、 三氯化铝 、 二异丙胺 作用下， 以 1,2-二氯乙烷 为溶剂， 反应 1.92h， 生成 ethyl (E)-4-hydroxy-3-methyl-6-oxo-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthalenyl)-2-hexenoate
  参考文献：
  名称：

  Conformational Effects on Retinoid Receptor Selectivity. 2. Effects of Retinoid Bridging Group on Retinoid X Receptor Activity and Selectivity

  摘要：

  The natural retinoid 9-cis-retinoic acid is an activating ligand for both the retinoic acid receptors (RARs) and the retinoid X receptors (RXRs), which are members of the retinoid/thyroid hormone/steroid hormone family of nuclear receptor proteins that activate gene transcription through specific response elements. The pharmacophoric groups necessary to confer RXR selectivity were established by evaluating the ability of 21 conformationally restricted retinoids to activate, the TREpal retinoic acid receptor response element for gene transcription in the presence of one of the three RAR subtypes or RXR alpha. In contrast to those retinoids selective for the RARs, these RXR-selective retinoids have one less atom in the bridge linking the hydrophobic and carboxylic acid termini of the retinoid skeleton. Therefore, a one-carbon bridge replaces the 19-methyl group and SE-double bond of S-cis-retinoic acid and is further functionalized by inclusion in an isopropylidene group, a dioxolane ring, or a cyclopropane ring for optimal RXR alpha activity and selectivity. In addition, the beta-geranylidene and 20-methyl-(11E,13E)-dienoic acid groups of g-cis-retinoic acid are replaced by a 5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2 naphthalenyl ring and a 4-carboxylphenyl ring, respectively, for optimal activation and selectivity. RXR alpha; selectivity is reduced on replacement of the 4-carboxylphenyl group by a 2-carboxyl-5-thienyl group or the S-cis-retinoic acid methylpentadienoic acid terminus.

  DOI：

  10.1021/jm00017a021

文献信息

• Bridged bicyclic aromatic compounds and their use in modulating gene
  申请人：SRI International

  公开号：US05466861A1

  公开（公告）日：1995-11-14

  Bridged bicyclic aromatic compounds are provided having the structure ##STR1## wherein R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5 and n are as defined herein. The novel compounds are useful for modulating gene expression of retinoic acid receptors, vitamin D receptors and thyroid receptors. Pharmaceutical compositions and methods for modulating gene expression are provided as well.

  提供具有以下结构的桥接双环芳香化合物：##STR1##其中R.sup.1、R.sup.2、R.sup.3、R.sup.4、R.sup.5和n的定义如本文所述。这些新颖化合物可用于调节视黄酸受体、维生素D受体和甲状腺受体的基因表达。同时还提供了用于调节基因表达的药物组合物和方法。