6-(ethyl(5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalen-2-yl)amino)nicotinic acid | 1246265-72-4

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: 6-(ethyl(5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalen-2-yl)amino)nicotinic acid
• 英文别名: NEt-TMN；6-[N-Ethyl(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)amino]nicotinic acid；6-[ethyl-(5,5,8,8-tetramethyl-6,7-dihydronaphthalen-2-yl)amino]pyridine-3-carboxylic acid
• CAS: 1246265-72-4
• 化学式: C₂₂H₂₈N₂O₂
• 分子量: 352.477
• InChiKey: RXCTZCYFGJAJCU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.9
• 重原子数：
  26
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  53.4
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  O-苄基羟胺 、 6-(ethyl(5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalen-2-yl)amino)nicotinic acid 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 5.0h， 以82%的产率得到6-[N-ethyl(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)amino]-N'-(phenylmethoxy)-3-pyridinecarboxamide
  参考文献：
  名称：

  Modification at the acidic domain of RXR agonists has little effect on permissive RXR-heterodimer activation

  摘要：

  Retinoid X receptors (RXRs) function as homo-or heterodimers with other nuclear receptors, such as peroxisome proliferator-activated receptors (PPARs), which are targets for treatment of hyperlipidemia and type 2 diabetes, or liver X receptors (LXRs), which are involved in glucose/lipid metabolism. PPAR/RXR or LXR/RXR are known as permissive RXR-heterodimers because they are activated by RXR agonists alone. Interestingly, the pattern of RXR-heterodimer activation is different depending on the RXR agonist structure, but the structure-activity relationship has not been reported. Here we show that modification or replacement of the carboxyl group in the acidic domain of RXR agonists has little or no effect on permissive RXR-heterodimer activation. Phosphonic acid (9), tetrazole (10), and hydroxamic acid (12) analogues were synthesized from the common bromo intermediate 7. Except for 9, these compounds showed RXR full-agonistic activities in the concentration range of 1-10 mu M. The order of agonistic activity toward both PPAR gamma/RXR alpha and LXR alpha/RXR alpha was the same as it was for RXR, that is, 11 > 10 > 12. These results should be useful for the development of RXR agonists with improved bioavailability. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.07.012
• 作为产物：
  描述：

  methyl 6-((5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalen-2-yl)amino)nicotinate 在 sodium hydride 、 potassium hydroxide 作用下， 以 甲醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.25h， 生成 6-(ethyl(5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalen-2-yl)amino)nicotinic acid
  参考文献：
  名称：

  建模，合成和潜在的类维生素A X受体（RXR）选择性激动剂的生物学评估：4- [1-（3,5,5,8,8-五甲基-5,6,7,8-tetrahydro-2）的类似物-萘基]乙炔基]苯甲酸（Bexarotene）和6-（乙基（5,5,8,8-四氢萘-2-基）氨基）烟酸（NEt-TMN）

  摘要：

  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

  DOI：

  10.1021/acs.jmedchem.6b00812

文献信息

• [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。
• 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。
• Therapeutic compounds
  申请人：ARIZONA BOARD OF REGENTS ON BEHALF OF ARIZONA STATE UNIVERSITY

  公开号：US10005741B2

  公开（公告）日：2018-06-26

  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.

  本发明提供了可用于治疗阿尔茨海默病、帕金森病、糖尿病、癌症和精神障碍（如精神分裂症）等疾病的化合物和组合物。
• Dihydroindene and tetrahydronaphthalene compounds
  申请人：ARIZONA BOARD OF REGENTS ON BEHALF OF ARIZONA STATE UNIVERSITY

  公开号：US10238655B2

  公开（公告）日：2019-03-26

  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.

  本发明提供了式 I 的化合物： 及其盐类，以及包含此类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相关的疾病。
• THERAPEUTIC COMPOUNDS
  申请人：ARIZONA BOARD OF REGENTS ON BEHALF OF ARIZONA STATE UNIVERSITY

  公开号：US20170008859A1

  公开（公告）日：2017-01-12

  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.