5,6,7,8-四氢-3,5,5,8,8-五甲基-2-萘胺 | 116233-17-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 四氢化萘
• 中文名称: 5,6,7,8-四氢-3,5,5,8,8-五甲基-2-萘胺
• 英文名称: 3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydronaphthalen-2-amine
• 英文别名: 5,6,7,8-tetrahydro-3,5,5,8,8-pentamethyl-2-naphthylamine；3-methyl-5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthylamine；3,5,5,8,8-pentamethyl-6,7-dihydronaphthalen-2-amine
• CAS: 116233-17-1
• 化学式: C₁₅H₂₃N
• 分子量: 217.354
• InChiKey: NDQSUCPZRPRYLX-UHFFFAOYSA-N

物化性质

• 熔点：
  96-97 °C
• 沸点：
  321.2±31.0 °C(Predicted)
• 密度：
  0.938±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  16
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  26
• 氢给体数：
  1
• 氢受体数：
  1

安全信息

• 海关编码：
  2921450090
• 危险性防范说明：
  P280
• 危险性描述：
  H302,H312,H332
• 储存条件：
  应存放在室温、避光且充满惰性气体的环境中。

反应信息

• 作为反应物：
  描述：

  5,6,7,8-四氢-3,5,5,8,8-五甲基-2-萘胺 在 tris(dibenzylideneacetone)dipalladium(0) chloroform complex 、 palladium on activated charcoal 、 氢气 、 caesium carbonate 、 R-(+)-1,1'-联萘-2,2'-双二苯膦 作用下， 以 乙酸乙酯 、 甲苯 为溶剂， 反应 4.0h， 生成 1-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydronaphthalen-2-yl)-1H-benzoimidazole-5-carboxylic acid methyl ester
  参考文献：
  名称：

  Mechanism of Retinoid X Receptor Partial Agonistic Action of 1-(3,5,5,8,8-Pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)-1H-benzotriazole-5-carboxylic Acid and Structural Development To Increase Potency

  摘要：

  We have reported that retinoid X receptor (RXR) partial agonist 1-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)-1H-benzotriazole-5-carboxylic acid (CBt-PMN, 4a) shows a significant antidiabetes effect in the KK-A(y) type 2 diabetes model mice, with reduced side effects compared to RXR full agonists. To elucidate the mechanism of the RXR partial agonist activity of 4a, we synthesized derivatives of 4a, evaluated their RXR agonist activity, and performed structure-activity relationship analysis. Reporter gene assay revealed that though 6b, which possesses an amino group at the 2-position of 5-carboxybenzimidazole, showed RXR full-agonist activity, compounds 6d and 6e, which possess an oxygen atom and a sulfur atom at the corresponding position, respectively, showed weak RXR agonist activity. On the other hand, 6c, which has a trifluoromethyl group at the corresponding position, acts as an RXR partial agonist, having similar E-max (67 +/- 2%) and lower EC50 (15 +/- 0 nM) compared to those of 4a (E-max = 75 +/- 4%, EC50 = 143 +/- 2 nM). A fluorescence polarization assay of cofactor recruitment confirmed that fluorescein-labeled D22 coactivator peptide was less efficiently recruited to RXR by 4a and 6c than by LGD1069 (1), a known RXR full agonist. Electrostatic potential field calculations and computational docking studies suggested that full agonists show an electrostatic attraction, which stabilizes the holo structure and favors coactivator recruitment, between the side chain at the benzimidazole 2-position and the a-carbonyl oxygen of asparagine-306 in helix 4 (H4) of the RXR receptor. However, RXR partial agonists 4a and 6c lack this interaction. Like 4a, 6c showed a significant antidiabetes effect in KK-A(y) type 2 diabetes model mice with reduced levels of the side effects associated with RXR full agonists. These findings should aid the design of new RXR partial agonists as antitype 2 diabetes drug candidates.

  DOI：

  10.1021/jm400033f
• 作为产物：
  描述：

  2,5-二氯-2,5-二甲基己烷 在 palladium on activated charcoal 三氯化铝 、 氢气 、 硝酸 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 生成 5,6,7,8-四氢-3,5,5,8,8-五甲基-2-萘胺
  参考文献：
  名称：

  氮杂类视黄醇作为新型类视黄醇X受体特异性激动剂。

  摘要：

  已经开发了一系列新的结构简单的有效亲脂性氮杂-类维生素A RXR激动剂。此处描述的N-烷基-氮杂二烯酸的SAR研究表明，RXR活性谱对N-烷基链长敏感。此外，我们将工作扩展到了氮杂二烯酸，其显示出许多可及的构象，从而使人们对该系列的SAR有更好的了解。

  DOI：

  10.1016/j.bmcl.2005.12.003

文献信息

• Retinoidal Pyrimidinecarboxylic Acids. Unexpected Diaza-Substituent Effects in Retinobenzoic Acids.
  作者：Kiminori OHTA、Emiko KAWACHI、Noriko INOUE、Hiroshi FUKASAWA、Yuichi HASHIMOTO、Akiko ITAI、Hiroyuki KAGECHIKA

  DOI：10.1248/cpb.48.1504

  日期：——

  Several pyridine-and pyrimidine-carboxylic acids were synthesized as ligand candidates for retinoid nuclear receptors, retinoic acid receptors (RARs) and retinoic X receptors (RXRs). Although the pyridine derivatives, 6-[(5, 6, 7, 8-tetrahydro-5, 5, 8, 8-tetramethyl-2-naphthalenyl)carbamoyl]pyridine-3-carboxylic acid (2b) and 6-[(5, 6, 7, 8-tetrahydro-5, 5, 8, 8-tetramethyl-2-naphthalenyl)carboxamido]pyridine-3-carboxylic acid (5b) are more potent than the corresponding benzoic acid-type retinoids, Am80 (2a) and Am580 (5a), the replacement of the benzene ring of Am580 (5a), Am555 (6a), or Am55 (7a) with a pyrimidine ring caused loss of the retinoidal activity both in HL-60 cell differentiation assay and in RAR transactivation assay using COS-1 cells. On the other hand, pyrimidine analogs (PA series, 10 and 11) of potent RXR agonists (retinoid synergists) with a diphenylamine skeleton (DA series, 8 and 9) exhibited potent retinoid synergistic activity in HL-60 cell differentiation assay and activated RXRs. Among the synthesized compounds, 2-[N-n-propyl-N-(5, 6, 7, 8-tetrahydro-5, 5, 8, 8-tetramethyl-2-naphthalenyl)amino]pyrimidene-5-carboxylic acid (PA013, 10e) is most active retinoid synergist in HL-60 assay.

  几种吡啶和嘧啶羧酸被合成为视黄酸核受体、视黄酸受体（RARs）和视黄酸X受体（RXRs）的配体候选物。虽然吡啶衍生物，6-[(5, 6, 7, 8-四氢-5, 5, 8, 8-四甲基-2-萘基)氨基甲酰]吡啶-3-羧酸（2b）和6-[(5, 6, 7, 8-四氢-5, 5, 8, 8-四甲基-2-萘基)羧酰胺]吡啶-3-羧酸（5b）比相应的苯甲酸型视黄酸更有效，如Am80（2a）和Am580（5a），但将Am580（5a）、Am555（6a）或Am55（7a）的苯环替换为嘧啶环会导致视黄酸活性在HL-60细胞分化试验和使用COS-1细胞的RAR转录激活试验中丧失。另一方面，具有二苯胺骨架（DA系列，8和9）的强效RXR激动剂（视黄酸协同剂）的嘧啶类似物（PA系列，10和11）在HL-60细胞分化试验中表现出强效的视黄酸协同活性并激活RXRs。在合成的化合物中，2-[N-正丙基-N-(5, 6, 7, 8-四氢-5, 5, 8, 8-四甲基-2-萘基)氨基]嘧啶-5-羧酸（PA013，10e）在HL-60试验中是最活跃的视黄酸协同剂。
• [EN] THERAPEUTIC COMPOUNDS<br/>[FR] COMPOSÉS THÉRAPEUTIQUES
  申请人：UNIV ARIZONA STATE

  公开号：WO2015130973A1

  公开（公告）日：2015-09-03

  The invention provides compounds and compositions that are useful for treating conditions including Alzheimer's disease, Parkinson's disease, diabetes, cancer, and psychotic disorders such as schizophrenia.

  这项发明提供了用于治疗包括阿尔茨海默病、帕金森病、糖尿病、癌症以及精神分裂症等疾病的化合物和组合物。
• Enantioselective Synthesis of Atropisomeric Biaryls by Pd‐Catalyzed Asymmetric Buchwald–Hartwig Amination
  作者：Peng Zhang、Xiao‐Mei Wang、Qi Xu、Chang‐Qiu Guo、Peng Wang、Chuan‐Jun Lu、Ren‐Rong Liu

  DOI：10.1002/anie.202108747

  日期：2021.9.27

  N−C Biaryl atropisomers are prevalent in natural products and bioactive drug molecules. However, the enantioselective synthesis of such molecules has not developed significantly. Particularly, the enantioselective synthesis of N−C biaryl atropisomers by stereoselective metal-catalyzed aryl amination remains unprecedented. Herein, a Pd-catalyzed cross-coupling strategy is presented for the synthesis

  NC 联芳基阻转异构体普遍存在于天然产物和生物活性药物分子中。然而，此类分子的对映选择性合成尚未显着发展。特别是，通过立体选择性金属催化芳基胺化反应对映选择性合成 NC 联芳基阻转异构体仍然是前所未有的。在此，提出了一种用于合成 NC 轴向手性联芳基分子的 Pd 催化交叉偶联策略。获得了广谱的 NC 轴向手性化合物，具有出色的对映选择性（高达 99 % ee）和良好的产率（高达 98 %）。该反应的实用性在有用的生物分子的合成中得到验证。
• Modeling, Synthesis, and Biological Evaluation of Potential Retinoid X Receptor (RXR)-Selective Agonists: Analogues of 4-[1-(3,5,5,8,8-Pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)ethynyl]benzoic Acid (Bexarotene) and 6-(Ethyl(5,5,8,8-tetrahydronaphthalen-2-yl)amino)nicotinic Acid (NEt-TMN)
  作者：Michael C. Heck、Carl E. Wagner、Pritika H. Shahani、Mairi MacNeill、Aleksandra Grozic、Tamana Darwaiz、Micah Shimabuku、David G. Deans、Nathan M. Robinson、Samer H. Salama、Joseph W. Ziller、Ning Ma、Arjan van der Vaart、Pamela A. Marshall、Peter W. Jurutka

  DOI：10.1021/acs.jmedchem.6b00812

  日期：2016.10.13

  cutaneous T-cell lymphoma (CTCL); however, 1 can provoke side effects by impacting RXR-dependent receptor pathways. All of the analogues in this study were evaluated for their potential to bind RXR through modeling and then assayed in an RXR–RXR mammalian-2-hybrid (M2H) system and in RXR-responsive element (RXRE)-mediated transcriptional experiments. The EC50 profiles for these unique analogues and their analogous

  4- [1-（3,5,5,8,8-五甲基-5,6,7,8-四氢-2-萘基）乙炔基]苯甲酸（贝沙罗汀，1）的磺酸类似物以及七个新的合成了两个报道的6-（乙基（5,5,8,8-四甲基-5,6,7,8-四氢萘-2-基）氨基）烟酸类似物（NEt-TMN）并评估了选择性类维生素A X受体（RXR）激动剂。化合物1经FDA批准用于治疗皮肤T细胞淋巴瘤（CTCL）；但是1可以通过影响RXR依赖的受体途径而引起副作用。通过建模评估了本研究中所有类似物与RXR结合的潜力，然后在RXR–RXR哺乳动物2杂交（M2H）系统和RXR反应元件（RXRE）介导的转录实验中进行了测定。这些独特的类似物的EC 50谱及其相对于1抑制CTCL细胞增殖的相似效力表明，这些化合物具有相似甚至增强的治疗潜力。几种化合物还显示出更高的选择性RXR激活，而视黄酸受体的交叉信号最小。这些结果表明，强大的RXR激动剂如NEt-TMN的修饰
• DIHYDROINDENE AND TETRAHYDRONAPHTHALENE COMPOUNDS
  申请人：ARIZONA BOARD OF REGENTS ON BEHALF OF ARIZONA STATE UNIVERSITY

  公开号：US20180207156A1

  公开（公告）日：2018-07-26

  The invention provides compounds of formula I: and salts thereof, as well as pharmaceutical compositions comprising such compounds. The compounds are useful for treating cancers, Alzheimer's disease, and conditions associated with demyelination.

  该发明提供了公式I的化合物及其盐，以及包含这些化合物的药物组合物。这些化合物可用于治疗癌症、阿尔茨海默病以及与脱髓鞘有关的疾病。