(S)-6-[(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)hydroxymethyl]-2-naphthalene carboxylic acid

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: (S)-6-[(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)hydroxymethyl]-2-naphthalene carboxylic acid
• 英文别名: (S)-BMS 184394；6-[(S)-hydroxy(5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalen-2-yl)methyl]naphthalene-2-carboxylic acid；6-[(S)-hydroxy-(5,5,8,8-tetramethyl-6,7-dihydronaphthalen-2-yl)methyl]naphthalene-2-carboxylic acid
• 化学式: C₂₆H₂₈O₃
• 分子量: 388.507
• InChiKey: AYAJZQYENGWICE-QHCPKHFHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.6
• 重原子数：
  29
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  57.5
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  methyl (R)-6-[(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)acetoxymethyl]-2-naphthalene carboxylate 在 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 20.0h， 生成 (S)-6-[(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)hydroxymethyl]-2-naphthalene carboxylic acid
  参考文献：
  名称：

  维甲酸受体β，γ-选择性配体：6-取代的2-萘甲酸类维生素A的合成和生物活性。

  摘要：

  为了寻找视黄酸受体（RAR）的选择性配体，合成了一系列6-取代的2-萘甲酸类维生素A，并在体外针对所有RAR的反式激活分析和竞争结合分析进行了评估。这些衍生物通常显示出RARβ，γ选择性。在这些萘甲酸中，肟衍生物12被确定为有效的RARγ-选择性类视黄醇，而烯烃衍生物11被发现与视黄酸相当，对RAR的β，γ选择性较低。对于生物测定，观察​​到配体对受体的结合亲和力与化合物在反式激活测定中的效力之间的一般相关性。将讨论这些萘甲酸的结构-活性关系。

  DOI：

  10.1021/jm9502293

文献信息

• Role of Retinoic Acid Receptor Gamma in the Rhino Mouse and Rabbit Irritation Models of Retinoid Activity
  作者：Peter R. Reczek、Jacek Ostrowski、Kuo-Long Yu、Simon Chen、Laura Hammer、Thor Roalsvig、John E. Starrett Jr.、Joyce Phelan Driscoll、Gary Whiting、Patrick G. Spinazze、Kenneth M. Tramposch、Muzammil M. Mansuri

  DOI：10.1159/000211360

  日期：——

  The three retinoic acid receptors (RARΑ, RARΒ and RARΓ) are known to modulate the transcription of target genes through interaction of the individual receptors with their naturally occurring ligand, retinoic acid (RA). Since RA has multiple effects in vivo, considerable effort has recently been devoted to finding selective compounds to elucidate the functions of individual receptors and to relate these functions to specific in vivo effects. The racemic synthetic retinoid 6-[(5,5,8,8-tetramethyl- 5,6,7,8-tetrahydro-2 – naphthyl)hydroxy-methyl]-2-naphthalene carboxylic acid has recently been identified as an RARΓ-selective agonist. A synthetic method involving lipase-mediated transformation has been developed to prepare the individual enantiomers. Discrimination between the two enantiomers is seen in both transcriptional activity and binding to recombinant receptors with the (S)-enantiomer being the more active. Differences between the two compounds are also seen in the Rhino mouse utriculi reduction assay and the rabbit irritation model. In both animal models, the (S)-enantiomer consistently gave a greater response. Taken together, these results suggest that the activity and irritation seen with RA and related compounds is receptor mediated. Further, the strong selectivity of the compounds reported here for RARΓ suggests that this receptor plays an important role in these in vivo biological activities. The discrimination between these enantiomers may be useful in the design of novel retinoids with uniquely defined biological properties.

  三种视黄酸受体（RARΑ，RARΒ和RARΥ）通过个体受体与其天然存在的配体视黄酸（RA）相互作用，已知可以调节靶基因的转录。由于RA在体内具有多种效应，近年来已经付出了大量努力，以寻找选择性化合物来阐明个体受体的功能，并将这些功能与特定的体内效应相关联。最近被确认为RARΥ选择性激动剂的光学异构合成视黄酸类似物6-[(5,5,8,8-四甲基-5,6,7,8-四氢-2-萘基)羟甲基]-2-萘甲酸已被鉴定出来。已开发了涉及脂肪酶介导的转化的合成方法，用于制备个体对映体。在转录活性和与重组受体的结合中，两个对映体之间的区别在（S）对映体更活跃方面得到体现。这两种化合物之间的差异也在Rhino小鼠耳石囊缩小实验和兔子刺激模型中得到体现。在这两种动物模型中，（S）对映体始终表现出更强的反应。综合这些结果表明，RA和相关化合物所见的活性和刺激是受体介导的。此外，这里报告的化合物对RARΥ的强选择性表明该受体在这些体内生物活性中起着重要作用。这些对映体之间的区别可能有助于设计具有独特定义的生物学性质的新型视黄酸类似物。
• From Aryl Bromides to Enantioenriched Benzylic Alcohols in a Single Flask: Catalytic Asymmetric Arylation of Aldehydes
  作者：Jeung Gon Kim、Patrick J. Walsh

  DOI：10.1002/anie.200600741

  日期：2006.6.19
• Retinoic Acid Receptor β,γ-Selective Ligands: Synthesis and Biological Activity of 6-Substituted 2-Naphthoic Acid Retinoids
  作者：Kuo-Long Yu、Patrick Spinazze、Jacek Ostrowski、Stephen J. Currier、Edward J. Pack、Laura Hammer、Thor Roalsvig、Jomary A. Honeyman、David R. Tortolani、Peter R. Reczek、Muzammil M. Mansuri、John E. Starrett

  DOI：10.1021/jm9502293

  日期：1996.1.1

  In search for retinoic acid receptor (RAR) selective ligands, a series of 6-substituted 2-naphthoic acid retinoids were synthesized and evaluated in vitro in a transactivation assay and a competition binding assay for all RARs. These derivatives, in general, showed RAR beta,gamma selectivity. Among these naphthoic acids, oxime derivative 12 was identified as a potent RAR gamma-selective retinoid, while

  为了寻找视黄酸受体（RAR）的选择性配体，合成了一系列6-取代的2-萘甲酸类维生素A，并在体外针对所有RAR的反式激活分析和竞争结合分析进行了评估。这些衍生物通常显示出RARβ，γ选择性。在这些萘甲酸中，肟衍生物12被确定为有效的RARγ-选择性类视黄醇，而烯烃衍生物11被发现与视黄酸相当，对RAR的β，γ选择性较低。对于生物测定，观察​​到配体对受体的结合亲和力与化合物在反式激活测定中的效力之间的一般相关性。将讨论这些萘甲酸的结构-活性关系。