5-[6-({[3-(2,6-dichlorophenyl)-5-(1-methylethyl)-4-isoxazolyl]methyl}oxy)-2-naphthalenyl]-2-fluorobenzoic acid | 1097777-41-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 5-[6-({[3-(2,6-dichlorophenyl)-5-(1-methylethyl)-4-isoxazolyl]methyl}oxy)-2-naphthalenyl]-2-fluorobenzoic acid
• 英文别名: 5-[6-[[3-(2,6-dichlorophenyl)-5-propan-2-yl-1,2-oxazol-4-yl]methoxy]naphthalen-2-yl]-2-fluorobenzoic acid
• CAS: 1097777-41-7
• 化学式: C₃₀H₂₂Cl₂FNO₄
• 分子量: 550.413
• InChiKey: WPOCXQRNLVKLEJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.4
• 重原子数：
  38
• 可旋转键数：
  7
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  72.6
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  methyl 5-[6-({[3-(2,6-dichlorophenyl)-5-(1-methylethyl)-4-isoxazolyl]methyl}oxy)-2-naphthalenyl]-2-fluorobenzoate 在 水 、 sodium hydroxide 、 盐酸 作用下， 以 四氢呋喃 、 甲醇 、 水 为溶剂， 以91%的产率得到5-[6-({[3-(2,6-dichlorophenyl)-5-(1-methylethyl)-4-isoxazolyl]methyl}oxy)-2-naphthalenyl]-2-fluorobenzoic acid
  参考文献：
  名称：

  [EN] FARNESOID X RECEPTOR AGONISTS
  [FR] AGONISTES DU RÉCEPTEUR DE FARNÉSOÏDE X

  摘要：

  本发明涉及法内索德X受体（FXR，NR1H4）。FXR是配体激活的转录因子核受体类的一个成员。更具体地说，本发明涉及作为FXR激动剂的化合物，包含该化合物的药物制剂，以及同一治疗用途。新颖的异恶唑化合物被披露作为药物组合物的一部分，用于治疗由FXR活性降低介导的状况，如肥胖、糖尿病、胆汁淤积性肝病、肝纤维化和代谢综合征。

  公开号：

  WO2009005998A1

文献信息

• FARNESOID X RECEPTOR AGONISTS
  申请人：Akwabi-Ameyaw Adwoa

  公开号：US20110034507A1

  公开（公告）日：2011-02-10

  The present invention relates to farnesoid X receptors (FXR, NR1H4). FXR is a member of the nuclear receptor class of ligand-activate transcription factors. More particularly, the present invention relates to compounds useful as agonists for FXR, pharmaceutical formulations comprising such compounds, and therapeutic use of the same. Novel isoxazole compounds are disclosed as part of pharmaceutical compositions for the treatment of a condition mediated by decreased FXR activity, such as obesity, diabetes, cholestatic liver disease, liver fibrosis, and metabolic syndrome.

  本发明涉及法尼索德X受体（FXR，NR1H4）。FXR是配体激活转录因子的核受体类成员。更具体地，本发明涉及作为FXR激动剂有用的化合物，包含这些化合物的制药组合物以及其治疗用途。新型异唑咪唑化合物被揭示为用于治疗由FXR活性降低介导的疾病状态的制药组合物，例如肥胖症、糖尿病、胆汁淤积性肝病、肝纤维化和代谢综合征。
• Perk activator for the treatment of neurodegenerative diseases
  申请人：DEUTSCHES ZENTRUM FÜR NEURODEGENERATIVE ERKRANKUNGEN E.V. (DZNE)

  公开号：US10369123B2

  公开（公告）日：2019-08-06

  The present invention relates to a novel method for the treatment and/or prophylaxis of a tau-mediated neurodegenerative disease and/or of a tau-mediated neurodegenerative pathological condition, especially of a neurodegenerative disease and/or of a neurodegenerative pathological condition associated with and/or accompanied by tau aggregation, and in particular for the treatment and/or prophylaxis of a tauopathy; compounds and/or agents and compositions for such treatment and/or prophylaxis, and the manufacture of the compounds and/or agents and compositions suitable for the said treatment and/or prophylaxis. In this regard, the present invention relates especially to the use of compounds acting as PERK activator, a prodrug thereof, a derivative thereof and/or a pharmaceutically acceptable salt of any thereof, as a medicament. In contrast to the prior art which addresses mainly PERK inhibition, or occasionally only the apoptotic arm of PERK of activation, the present invention pertains to the effects of indirect or direct PERK activation achieved via the neuroprotective arm of PERK signaling.

  本发明涉及一种治疗和/或预防tau介导的神经退行性疾病和/或tau介导的神经退行性病理状态的新方法，特别是与tau聚集相关和/或伴有tau聚集的神经退行性疾病和/或神经退行性病理状态，尤其是治疗和/或预防tau病；用于这种治疗和/或预防的化合物和/或制剂及组合物，以及适用于上述治疗和/或预防的化合物和/或制剂及组合物的制造。在这方面，本发明尤其涉及作为 PERK 激活剂的化合物、其原药、其衍生物和/或其药学上可接受的盐作为药物的用途。现有技术主要涉及 PERK 抑制，或者偶尔只涉及 PERK 激活的凋亡部分，而本发明则涉及通过 PERK 信号转导的神经保护部分实现的间接或直接 PERK 激活的效果。
• EP3193869A1
  申请人：——

  公开号：EP3193869A1

  公开（公告）日：2017-07-26
• PERK ACTIVATOR FOR THE TREATMENT OF NEURODEGENERATIVE DISEASES
  申请人：DEUTSCHES ZENTRUM FÜR NEURODEGENERATIVE ERKRANKUNGEN E.V. (DZNE)

  公开号：US20170304241A1

  公开（公告）日：2017-10-26

  The present invention relates to a novel method for the treatment and/or prophylaxis of a tau-mediated neurodegenerative disease and/or of a tau-mediated neurodegenerative pathological condition, especially of a neurodegenerative disease and/or of a neurodegenerative pathological condition associated with and/or accompanied by tau aggregation, and in particular for the treatment and/or prophylaxis of a tauopathy; compounds and/or agents and compositions for such treatment and/or prophylaxis, and the manufacture of the compounds and/or agents and compositions suitable for the said treatment and/or prophylaxis. In this regard, the present invention relates especially to the use of compounds acting as PERK activator, a prodrug thereof, a derivative thereof and/or a pharmaceutically acceptable salt of any thereof, as a medicament. In contrast to the prior art which addresses mainly PERK inhibition, or occasionally only the apoptotic arm of PERK of activation, the present invention pertains to the effects of indirect or direct PERK activation achieved via the neuroprotective arm of PERK signaling.
• [EN] PERK ACTIVATOR FOR THE TREATMENT OF NEURODEGENERATIVE DISEASES<br/>[FR] ACTIVATEUR DU SIGNAL PERK POUR LE TRAITEMENT DE MALADIES NEURODÉGÉNÉRATIVES
  申请人：DEUTSCHES ZENTRUM FÜR NEURODEGENERATIVE ERKRANKUNGEN E V DZNE

  公开号：WO2016024010A1

  公开（公告）日：2016-02-18

  The present invention relates to a novel method for the treatment and/or prophylaxis of a tau-mediated neurodegenerative disease and/or of a tau-mediated neurodegenerative pathological condition, especially of a neurodegenerative disease and/or of a neurodegenerative pathological condition associated with and/or accompanied by tau aggregation, and in particular for the treatment and/or prophylaxis of a tauopathy; compounds and/or agents and compositions for such treatment and/or prophylaxis, and the manufacture of the compounds and/or agents and compositions suitable for the said treatment and/or prophylaxis. In this regard, the present invention relates especially to the use of compounds acting as PERK activator, a prodrug thereof, a derivative thereof and/or a pharmaceutically acceptable salt of any thereof, as a medicament. In contrast to the prior art which addresses mainly PERK inhibition, or occasionally only the apoptotic arm of PERK of activation, the present invention pertains to the effects of indirect or direct PERK activation achieved via the neuroprotective arm of PERK signaling.