ethyl 5-<(5,6,7,8-tetrahydro-3,5,5,8,8-pentamethyl-2-naphthalenyl)carbonyl>thiophene-2-carboxylate | 156910-45-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: ethyl 5-<(5,6,7,8-tetrahydro-3,5,5,8,8-pentamethyl-2-naphthalenyl)carbonyl>thiophene-2-carboxylate
• 英文别名: Ethyl 5-[(5,6,7,8-tetrahydro-3,5,5,8,8-pentamethyl-2-naphthalenyl)carbonyl]thiophen-2-carboxylate；ethyl 5-(3,5,5,8,8-pentamethyl-6,7-dihydronaphthalene-2-carbonyl)thiophene-2-carboxylate
• CAS: 156910-45-1
• 化学式: C₂₃H₂₈O₃S
• 分子量: 384.54
• InChiKey: KAGJAZMQYPEXQA-UHFFFAOYSA-N

物化性质

• 沸点：
  498.8±45.0 °C(predicted)
• 密度：
  1.094±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  7.3
• 重原子数：
  27
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  71.6
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  ethyl 5-<(5,6,7,8-tetrahydro-3,5,5,8,8-pentamethyl-2-naphthalenyl)carbonyl>thiophene-2-carboxylate 在 氢氧化钾 作用下， 以 甲醇 为溶剂， 以1%的产率得到SR11245
  参考文献：
  名称：

  Bridged bicyclic aromatic compounds and their use in modulating gene

  摘要：

  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。

  公开号：

  US05466861A1
• 作为产物：
  描述：

  2,5-噻吩二羧酸乙酯 在 三氯化铝 、 草酰氯 、 N,N-二甲基甲酰胺 作用下， 以 二氯甲烷 、 1,2-二氯乙烷 为溶剂， 反应 16.0h， 生成 ethyl 5-<(5,6,7,8-tetrahydro-3,5,5,8,8-pentamethyl-2-naphthalenyl)carbonyl>thiophene-2-carboxylate
  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。
• RXR HOMODIMER FORMATION AND BRIDGED BICYCLIC AROMATIC COMPOUNDS AND THEIR USE IN MODULATING GENE EXPRESSION
  申请人：LA JOLLA CANCER RESEARCH FOUNDATION

  公开号：EP0671005A1

  公开（公告）日：1995-09-13
• US5466861A
  申请人：——

  公开号：US5466861A

  公开（公告）日：1995-11-14
• US5837725A
  申请人：——

  公开号：US5837725A

  公开（公告）日：1998-11-17
• [EN] RXR HOMODIMER FORMATION AND BRIDGED BICYCLIC AROMATIC COMPOUNDS AND THEIR USE IN MODULATING GENE EXPRESSION<br/>[FR] FORMATION D'UN HOMODIMERE CONTENANT DES RECEPTEURS DE RETINOIDE X (RXR), COMPOSES AROMATIQUES BICYCLIQUES PONTES ET LEUR UTILISATION DANS LA MODULATION DE L'EXPRESSION GENIQUE
  申请人：——

  公开号：WO1994012880A2

  公开（公告）日：1994-06-09

  [EN] The invention provides a method of screening a substance for the ability to affect the formation of a retinoid X receptor homodimer comprising combining the substance and a solution containing retinoid X receptors and determining the presence of homodimer formation. The screening method can be used to determine compounds which selectively activate homodimer formation and heterodimer formation. Also provided is a method of screening a substance for an effect on a retinoid X receptor homodimer's ability to bind DNA comprising combining the substance with the homodimer and determining the effect of the compound on the homodimer's ability to bind DNA. Finally, the invention provides methods of activating retinoid X receptor homodimer formation. Bridged bicyclic aromatic compounds are provided having structure (I); wherein R<1>, R<2>, R<3>, R<4>, R<5> and n are as defined herein. The 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.
  [FR] L'invention se rapporte à un procédé de criblage d'une substance, permettant de détecter l'aptitude à affecter la formation d'un homodimère contenant des récepteurs de rétinoïde X, et consistant à combiner la substance et une solution contenant les récepteurs de rétinoïde X et à déterminer la formation de l'homodimère. Ce procédé de criblage peut être utilisé pour déterminer quels sont les composés qui activent sélectivement la formation d'un homodimère et celle d'un hétérodimère. Un procédé de criblage d'une substance est également décrit, lequel permet de déterminer l'effet du composé sur l'aptitude de l'homodimère à lier l'ADN et consiste à combiner ladite substance à l'homodimère et à déterminer l'effet du composé sur l'aptitude de l'homodimère à lier l'ADN. Enfin, l'invention se rapporte à des procédés d'activation de la formation d'un homodimère contenant des récepteurs de rétinoïde X. Des composés aromatiques bicycliques pontés sont décrits, ces composés présentant la structure (I) dans laquelle R1, R2, R3, R4, R5 et n sont tels que décrits dans le descriptif. Ces composés permettent de moduler l'expression génique de récepteurs d'acide rétinoïque, de récepteurs de vitamine D et de récepteurs de thyroïde. Des procédés et des compositions pharmaceutiques permettant de moduler l'expression génique sont également décrits.