4-(1-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalen-2-yl)vinyl)benzoic acid | 156910-52-0

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: 4-(1-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalen-2-yl)vinyl)benzoic acid
• 英文别名: TTNEB；4-[1-(5,6.7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)ethenyl]benzoic acid；4-[1-(5,5,8,8-Tetramethyl-5,6,7,8-tetrahydro-naphthalen-2-yl)-vinyl]-benzoic acid；4-[1-(5,5,8,8-tetramethyl-6,7-dihydronaphthalen-2-yl)ethenyl]benzoic acid
• CAS: 156910-52-0
• 化学式: C₂₃H₂₆O₂
• 分子量: 334.458
• InChiKey: SPARUJQOIBYQHO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.2
• 重原子数：
  25
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  37.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  4-(1-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalen-2-yl)vinyl)benzoic acid 在 palladium on activated charcoal 氢气 作用下， 以 乙醇 为溶剂， 以74%的产率得到SR11223
  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：

  4-氯甲酰基苯甲酸甲酯 在 aluminum (III) chloride 、 正丁基锂 、 水 、 二异丙胺 、 potassium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 正己烷 、 二氯甲烷 为溶剂， 反应 1.92h， 生成 4-(1-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalen-2-yl)vinyl)benzoic acid
  参考文献：
  名称：

  潜在维甲酸-X-受体 (RXR) 选择性激动剂的建模、合成和生物学评价：4-[1-(3,5,5,8,8-Pentamethyl-5,6,7,8-tetrahyro-2) 的类似物-萘基）乙炔基]苯甲酸（Bexarotene）和 6-（乙基（4-异丁氧基-3-异丙基苯基）氨基）烟酸（NEt-4IB）

  摘要：

  除了 4-[1-(3,5,5,8,8 -pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)ethynyl]benzoic acid (bexarotene) 与FDA 批准的药物bexarotene ( 1 )一起制备并评估了选择性维甲酸-X-受体 (RXR) 激动作用用于皮肤 T 细胞淋巴瘤 (CTCL)。Bexarotene 治疗通过激发或破坏其他 RXR 依赖性途径引起副作用。类似物通过与 RXR 的结合建模进行评估，然后在基于人类细胞的 RXR-RXR 哺乳动物-2-杂交 (M2H) 系统以及 RXRE 控制的转录系统中进行评估。还在 KMT2A-MLLT3 白血病细胞和 EC 50和 IC 50中测试了类似物确定这些化合物的值。此外，评估了类似物在 LXRE 系统中激活 LXR 作为 ApoE 表达的驱动因素，并随后用作神经退行性疾病的潜在治疗剂，结果表明这些化合物发挥了一系列不同的

  DOI：

  10.3390/ijms222212371

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.

  提供结构为##STR1##的桥接双环芳香化合物，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。这些新型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。还提供了调节基因表达的制药组合物和方法。
• Assay for identification of compounds that promote melanin production and retinoid-like compounds identified by said assay
  申请人：Galderma Research & Development, S.N.C.

  公开号：US20030113281A1

  公开（公告）日：2003-06-19

  An in vitro assay for selecting compounds that alter pigmentation of skin is provided. Also, a novel class of pro-pigmentatory compounds is provided which comprise substituted aromatic or heterocyclic carboxylic acids, or derivatives thereof, or pharmaceutically acceptable salts, which do not contain a pheno, naphthol, thiophenol, or a thionaphthol function in free or protected form. In a preferred embodiment, thess compounds will display activity for RXRs. These compounds may be used for altering pigmentation of human skin and/or hair in cosmetic or dermatological compositions, and for the treatment of disorders and disease conditions that affect skin or hair pigmentation.

  提供了一种体外测定法，用于选择改变皮肤色素的化合物。此外，还提供了一类新型的促色素化合物，包括取代芳香或杂环羧酸或其衍生物或药学上可接受的盐，不含自由或保护形式的苯酚，萘酚，硫酚或硫代萘酚功能。在一种优选实施例中，这些化合物将显示出对RXRs的活性。这些化合物可用于改变人类皮肤和/或头发的色素，用于化妆品或皮肤科组合物，并用于治疗影响皮肤或头发色素的疾病和疾病状态。
• Treatment of disease states which result from neoplastic cell proliferation using PPAR-gamma activators and compositions useful therefor
  申请人：The Salk Institute for Biological Studies

  公开号：US20040162354A1

  公开（公告）日：2004-08-19

  In accordance with the present invention, it has been discovered that PPAR&ggr; is expressed consistently in tissues associated with each of a variety of disease states which result from neoplastic cell proliferation. It has further been discovered that maximal activation of PPAR&ggr; with exogenous ligand promotes terminal differentiation of primary cells which are otherwise subject to neoplastic cell proliferation. In accordance with another aspect of the invention, it has been discovered that RXR-specific ligands are also potent agents for induction of differentiation of cells expressing the PPAR&ggr;/RXR&agr; heterodimer, and that simultaneous treatment of cells subject to neoplastic cell proliferation with a PPAR&ggr;-selective ligand, in combination with an RXR-specific ligand, results in an additive stimulation of differentiation. Thus, the effect of neoplastic cell proliferation can be ameliorated by treatment of cells undergoing neoplastic cell proliferation with PPAR&ggr; agonists, optionally in the further presence of RXR agonists, thereby blocking further proliferation thereof. Accordingly, compounds and compositions which are useful for the treatment of a variety of disease states which result from neoplastic cell proliferation have been identified and are described herein.

  根据本发明，人们发现 PPAR&ggr; 在与肿瘤细胞增殖导致的各种疾病状态有关的组织中持续表达。本发明还进一步发现，PPAR&ggr; 在外源性配体的最大激活作用下，可促进原代细胞的终末分化，否则这些细胞就会受到肿瘤细胞增殖的影响。根据本发明的另一方面，发现 RXR 特异性配体也是诱导表达 PPAR&ggr;/RXR&agr; 异二聚体的细胞分化的有效药物，而且用 PPAR&ggr;- 选择性配体结合 RXR 特异性配体同时处理受肿瘤性细胞增殖影响的细胞，会对分化产生叠加刺激作用。因此，用 PPAR&ggr;激动剂（可选择在 RXR 激动剂进一步存在的情况下）处理发生肿瘤细胞增殖的细胞，可以改善肿瘤细胞增殖的影响，从而阻止其进一步增殖。因此，已经发现并在此描述了可用于治疗由肿瘤细胞增殖引起的各种疾病状态的化合物和组合物。
• Boehm; Zhang; Badea, Journal of Medicinal Chemistry, 1994, vol. 37, # 18, p. 2930 - 2941
  作者：Boehm、Zhang、Badea、White、Mais、Berger、Suto、Goldman、Heyman

  DOI：——

  日期：——
• Composition pharmaceutique ou cosmétique contenant en association un rétinoîde et un stérol
  申请人：CENTRE INTERNATIONAL DE RECHERCHES DERMATOLOGIQUES GALDERMA - CIRD GALDERMA

  公开号：EP0465343B1

  公开（公告）日：1994-06-15