3-(((3-Chloro-5-((3-(2,6-dichlorophenyl)-5-isopropylisoxazol-4-yl)methoxy)pyridin-2-yl)(methyl)amino)methyl)benzoic acid | 1010108-93-6

• 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: 3-(((3-Chloro-5-((3-(2,6-dichlorophenyl)-5-isopropylisoxazol-4-yl)methoxy)pyridin-2-yl)(methyl)amino)methyl)benzoic acid
• 英文别名: 3-[[[3-chloro-5-[[3-(2,6-dichlorophenyl)-5-propan-2-yl-1,2-oxazol-4-yl]methoxy]pyridin-2-yl]-methylamino]methyl]benzoic acid
• CAS: 1010108-93-6
• 化学式: C₂₇H₂₄Cl₃N₃O₄
• 分子量: 560.864
• InChiKey: IIBBKFGPSAHSTP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.9
• 重原子数：
  37
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  88.7
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  methyl 3-(((3-chloro-5-((3-(2,6-dichlorophenyl)-5-isopropylisoxazol-4-yl)methoxy)pyridin-2-yl)(methyl)amino)methyl)benzoate 在 水 、 lithium hydroxide 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 6.0h， 生成 3-(((3-Chloro-5-((3-(2,6-dichlorophenyl)-5-isopropylisoxazol-4-yl)methoxy)pyridin-2-yl)(methyl)amino)methyl)benzoic acid
  参考文献：
  名称：

  Synthesis and pharmacological validation of a novel series of non-steroidal FXR agonists

  摘要：

  To overcome the known liabilities of GW4064 a series of analogs were synthesized where the stilbene double bond is replaced by an oxymethylene or amino-methylene linker connecting a terminal benzoic acid with a substituted heteroaryl in the middle ring position. As a result we discovered compounds with increased potency in vitro that cause dose-dependent reduction of plasma triglycerides and cholesterol in db/db mice down to 2 x 1 mg/kg/day upon oral administration. (c) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.06.084

文献信息

• Heterocyclic FXR Binding Compounds
  申请人：Kremoser Claus

  公开号：US20100184809A1

  公开（公告）日：2010-07-22

  The present invention relates to compounds which bind to the NR1H4 receptor (FXR) and act as agonists or partial agonists of the NR1H4 receptor (FXR). The invention further relates to the use of the compounds for the preparation of a medicament for the treatment of diseases and/or conditions through binding of said nuclear receptor by said compounds, and to a process for the synthesis of said compounds.

  本发明涉及一种能够与NR1H4受体（FXR）结合并作为NR1H4受体（FXR）的激动剂或部分激动剂的化合物。本发明还涉及使用这些化合物制备药物来治疗疾病和/或通过这些化合物结合所述核受体来治疗疾病和/或状况的方法，以及一种用于合成这些化合物的方法。
• HETEROCYCLIC FXR BINDING COMPOUNDS
  申请人：Phenex Pharmaceuticals AG

  公开号：EP2084147A1

  公开（公告）日：2009-08-05
• [EN] HETEROCYCLIC FXR BINDING COMPOUNDS<br/>[FR] COMPOSÉS HÉTÉROCYCLIQUES SE LIANT AU FXR
  申请人：PHENEX PHARMACEUTICALS AG

  公开号：WO2008025540A1

  公开（公告）日：2008-03-06

  [EN] The present invention relates to compounds which bind to the NR1H4 receptor (FXR) and act as agonists or partial agonists of the NR1H4 receptor (FXR). The invention further relates to the use of the compounds for the preparation of a medicament for the treatment of diseases and/or conditions through binding of said nuclear receptor by said compounds, and to a process for the synthesis of said compounds.
  [FR] La présente invention concerne des composés qui se lient au récepteur NR1H4 (FXR) et agissent en tant qu'agonistes ou agonistes partiels du récepteur NR1H4 (FXR). L'invention concerne également l'utilisation des composés pour la préparation d'un médicament pour le traitement de maladies et/ou de troubles par liaison dudit récepteur nucléaire avec lesdits composés, et un procédé de synthèse desdits composés.
• Synthesis and pharmacological validation of a novel series of non-steroidal FXR agonists
  作者：Ulrich Abel、Thomas Schlüter、Andreas Schulz、Eva Hambruch、Christoph Steeneck、Martin Hornberger、Thomas Hoffmann、Sanja Perović-Ottstadt、Olaf Kinzel、Michael Burnet、Ulrich Deuschle、Claus Kremoser

  DOI：10.1016/j.bmcl.2010.06.084

  日期：2010.8

  To overcome the known liabilities of GW4064 a series of analogs were synthesized where the stilbene double bond is replaced by an oxymethylene or amino-methylene linker connecting a terminal benzoic acid with a substituted heteroaryl in the middle ring position. As a result we discovered compounds with increased potency in vitro that cause dose-dependent reduction of plasma triglycerides and cholesterol in db/db mice down to 2 x 1 mg/kg/day upon oral administration. (c) 2010 Elsevier Ltd. All rights reserved.