methyl 4-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalene-2-carbonyl)benzoate | 117259-83-3

• 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: methyl 4-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalene-2-carbonyl)benzoate
• 英文别名: methyl 4-[(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)carbonyl]benzoate；Methyl 4-[(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)carbonyl]benzoate；methyl 4-(5,5,8,8-tetramethyl-6,7-dihydronaphthalene-2-carbonyl)benzoate
• CAS: 117259-83-3
• 化学式: C₂₃H₂₆O₃
• 分子量: 350.458
• InChiKey: IVHHFAZLFWXCIR-UHFFFAOYSA-N

物化性质

• 沸点：
  480.9±45.0 °C(Predicted)
• 密度：
  1.064±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  6.2
• 重原子数：
  26
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  43.4
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  methyl 4-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalene-2-carbonyl)benzoate 在 sodium tetrahydroborate 作用下， 以 乙醚 、 乙醇 为溶剂， 反应 2.0h， 以85%的产率得到methyl 4-benzoate
  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：

  对苯二甲酸单甲酯 在 aluminum (III) chloride 、 氯化亚砜 作用下， 以 二氯甲烷 为溶剂， 反应 0.25h， 生成 methyl 4-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalene-2-carbonyl)benzoate
  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
• 作为试剂：
  描述：

  1,1,4,4-四甲基-1,2,3,4-四氢萘 、 Terephthalic acid monomethylester chloride 、 三氯化铝 、 在 ice 、 乙酸乙酯 、 水 、 Brine 、 methyl 4-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalene-2-carbonyl)benzoate 作用下， 以 二氯甲烷 为溶剂， 反应 1.17h， 以to give methyl 4-[(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)carbonyl]benzoate (Compound 43, 18.5 g, 99%)的产率得到methyl 4-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalene-2-carbonyl)benzoate
  参考文献：
  名称：

  Compounds activating pharmacological effect of retinoids

  摘要：

  化合物的化学式为(I)或(II)或其盐，其中R'代表氢原子或C.sub.1-6烷基；R.sup.2和R.sup.3分别代表氢原子或C.sub.1-6烷基，或R.sup.2和R.sup.1结合在一起表示5或6成员环烷基；R.sup.4代表例如氢原子或C.sub.1-6烷基；R.sup.4代表例如氢原子或C.sub.1-6烷基；R.sup.6代表氢原子或C.sub.1-6烷基；X代表--NR.sup.7 --，--O--，--CHR.sup.7 --或--S--，其中R.sup.7代表例如氢原子或C.sub.1-6烷基；Y代表苯基或吡啶二基。这些化合物可用作增强视黄醇化合物活性的剂。 ##STR1##

  公开号：

  US06121256A1

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。
• Compounds activating pharmacological effects of retinoids
  申请人：Institute of Medicinal Molecular Design, Inc.

  公开号：US05929069A1

  公开（公告）日：1999-07-27

  A compound represented by the formula (I) or (II) or a salt thereof wherein R.sup.1 represents hydrogen atom or a C.sub.1-6 alkyl group; R.sup.2 and R.sup.3 independently represent a hydrogen atom or a C.sub.1-6 alkyl group, or R.sup.2 and R.sup.3 may combine together to represent a 5- or 6-membered cycloalkyl group; R.sup.4 represents, for example, a hydrogen atom or a C.sub.1-6 alkyl group; R.sup.5 represents, for example, a hydrogen atom or a C.sub.1-6 alkyl group; R.sup.6 represents a hydrogen atom or a C.sub.1-6 alkyl group; x represents --NR.sup.7 --, --O--, --CHR.sup.7 -- or --S-- in which R.sup.7 represents, for example, a hydrogen atom or a C.sub.1-6 alkyl group; and Y represents a phenylene group or a pyridinediyl group. The compounds are useful as agents for enhancing the activities of retinoid compounds. ##STR1##

  化合物的分子式为(I)或(II)，或其盐，其中R.sup.1代表氢原子或C.sub.1-6烷基；R.sup.2和R.sup.3分别代表氢原子或C.sub.1-6烷基，或R.sup.2和R.sup.3可以结合在一起代表5-或6-成员环烷基；R.sup.4代表，例如，氢原子或C.sub.1-6烷基；R.sup.5代表，例如，氢原子或C.sub.1-6烷基；R.sup.6代表氢原子或C.sub.1-6烷基；x代表--NR.sup.7 --，--O--，--CHR.sup.7 --或--S--，其中R.sup.7代表，例如，氢原子或C.sub.1-6烷基；Y代表苯基或吡啶二基团。这些化合物可用作增强视黄醇化合物活性的试剂。
• Regulation of Retinoidal Actions by Diazepinylbenzoic Acids. Retinoid Synergists Which Activate the RXR−RAR Heterodimers
  作者：Hiroki Umemiya、Hiroshi Fukasawa、Masayuki Ebisawa、Laurence Eyrolles、Emiko Kawachi、Ghislaine Eisenmann、Hinrich Gronemeyer、Yuichi Hashimoto、Koichi Shudo、Hiroyuki Kagechika

  DOI：10.1021/jm9704309

  日期：1997.12.1

  15-pentamethyldinaphtho[2,3-b][1,2-e]diazepin-7-yl) benzoic acid (LE540, 17), exhibits a 1 order of magnitude higher antagonistic potential than the parental LE135 (6). In contrast, 4-[5H-2,3-(2,5-dimethyl-2,5-hexano)-5-methyldibenzo[b,e] [1,4]diazepin-11-yl]-benzoic acid (HX600, 7), a structural isomer of the antagonistic LE135 (6), enhanced HL-60 cell differentiation induced by RAR agonists, such as Am80 (2)

  在人HL-60早幼粒细胞白血病细胞中，二氮杂pin基苯甲酸衍生物可以对天然或合成类维生素A的诱导分化活性表现出拮抗或协同作用，该活性很大程度上取决于二氮杂ring环上取代基的性质。因此，类视黄醇拮抗剂LE135（6），4-（13H-10,11,12,13-tetrahydro-10，10,13,13,15-五甲基二萘并[2,3-b] [1,2 -e] diazepin-7-yl）苯甲酸（LE540，17）的拮抗潜力比亲代LE135（6）高1个数量级。相反，4- [5H-2,3-（2,5-二甲基-2,5-己基）-5-甲基二苯并[b，e] [1,4]二氮杂-11-基]-苯甲酸（HX600 ，LEAF（6）的结构异构体，（7）增强了RAR激动剂（例如Am80）诱导的HL-60细胞分化（2）。噻嗪类化合物HX630（29）和氮杂类衍生物HX640（30）的协同作用进一步增强。两者都比HX600（7
• Development and Characterization of Novel and Selective Inhibitors of Cytochrome P450 CYP26A1, the Human Liver Retinoic Acid Hydroxylase
  作者：Philippe Diaz、Weize Huang、Charles M. Keyari、Brian Buttrick、Lauren Price、Nicolas Guilloteau、Sasmita Tripathy、Vanessa G. Sperandio、Frank R. Fronczek、Fanny Astruc-Diaz、Nina Isoherranen

  DOI：10.1021/acs.jmedchem.5b01780

  日期：2016.3.24

  and CYP26B1 is unknown, and no selective CYP26A1 or CYP26B1 inhibitors have been developed. Here the synthesis and potent inhibitory activity of the first CYP26A1 selective inhibitors is reported. A series of nonazole CYP26A1 selective inhibitors was identified with low nM potency. The lead compound 3-4-[2-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalen-2-yl)-1,3-dioxolan-2-yl] phenyl}4-propanoic

  细胞色素P450 CYP26酶负责全反式维甲酸（t RA）的清除。抑制CYP26酶会增加内源性t RA浓度，并且是有吸引力的治疗靶标。但是，尚不存在现有的t RA代谢抑制剂对CYP26A1和CYP26B1的选择性和效力，因此尚未开发出选择性的CYP26A1或CYP26B1抑制剂。此处报道了首批CYP26A1选择性抑制剂的合成和强抑制活性。鉴定出一系列的nazole CYP26A1选择性抑制剂具有低nM效能。铅化合物3- 4- [2-（5,5,8,8-四甲基-5,6,7,8-四氢萘-2-基）-1,3-二氧戊环-2-基]苯基} 4 -丙酸（24）对CYP26A1有43倍的选择性，IC 50为340 nM。化合物24及其两个结构类似物也抑制了HepG2细胞中的t RA代谢，导致t RA增强RAR激活的能力。所鉴定的化合物具有成为旨在提高内源性t RA浓度的新型治疗方法的潜力，并且可用作与t RA共同治疗以抵抗治疗耐药性的方法。
• RXR homodimer formation
  申请人：La Jolla Cancer Research Foundation

  公开号：US05824484A1

  公开（公告）日：1998-10-20

  The invention provides a method of screening a substance for the ability to effect 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. 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. A method of inhibiting an activity of a retinoid X receptor heterodimer comprising increasing the formation of a retinoid X receptor homodimer, thereby preventing the retinoid X receptor from forming a heterodimer and preventing the resulting heterodimer activity is also provided. A method of inhibiting an activity of a retinoid X receptor homodimer is also provided. A method of determining an increased probability of a pathology associated with retinoid X receptor homodimer formation and treating such pathology are further provided. In addition, a method of screening a response element for binding with a retinoid X receptor homodimer is provided. Finally, the invention provides methods of activating retinoid X receptor homodimer formation.

  本发明提供了一种筛选物质对影响视黄酸X受体同源二聚体形成能力的方法，包括将该物质与含有视黄酸X受体的溶液结合，并确定同源二聚体形成的存在。还提供了一种筛选物质对视黄酸X受体同源二聚体结合DNA能力的影响的方法，包括将该物质与同源二聚体结合，并确定该化合物对同源二聚体结合DNA能力的影响。本发明还提供了一种抑制视黄酸X受体异源二聚体活性的方法，包括增加视黄酸X受体同源二聚体的形成，从而防止视黄酸X受体形成异源二聚体并防止由此产生的异源二聚体活性。本发明还提供了一种抑制视黄酸X受体同源二聚体活性的方法。此外，本发明还提供了一种确定与视黄酸X受体同源二聚体形成相关的病理概率增加并治疗此类病理的方法。此外，本发明还提供了一种筛选响应元件与视黄酸X受体同源二聚体结合的方法。最后，本发明提供了激活视黄酸X受体同源二聚体形成的方法。