3-((1s,3s)-3-(2-chloro-4-((5-cyclopropyl-3-(2,6-dichlorophenyl)isoxazol-4-yl)methoxy)phenyl)-3-hydroxycyclobutyl)benzoic acid | 1418274-47-1

• 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-((1s,3s)-3-(2-chloro-4-((5-cyclopropyl-3-(2,6-dichlorophenyl)isoxazol-4-yl)methoxy)phenyl)-3-hydroxycyclobutyl)benzoic acid
• CAS: 1418274-47-1
• 化学式: C₃₀H₂₄Cl₃NO₅
• 分子量: 584.883
• InChiKey: BLUPXUIEWBLQAV-ZOXYEEGJSA-N

物化性质

• 沸点：
  765.8±60.0 °C(Predicted)
• 密度：
  1.472±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  8.22
• 重原子数：
  39.0
• 可旋转键数：
  8.0
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  92.79
• 氢给体数：
  2.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  甲基磺酰胺 、 3-((1s,3s)-3-(2-chloro-4-((5-cyclopropyl-3-(2,6-dichlorophenyl)isoxazol-4-yl)methoxy)phenyl)-3-hydroxycyclobutyl)benzoic acid 在 4-二甲氨基吡啶 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 以33%的产率得到3-((1s,3s)-3-(2-chloro-4-((5-cyclopropyl-3-(2,6-dichlorophenyl)isoxazol-4-yl)methoxy)phenyl)-3-hydroxycyclobutyl)-N-(methylsulfonyl)benzamide
  参考文献：
  名称：

  NOVEL FXR (NR1H4) BINDING AND ACTIVITY MODULATING COMPOUNDS

  摘要：

  本发明涉及结合NR1H4受体（FXR）并作为FXR激动剂的化合物。该发明还涉及利用这些化合物制备药物以治疗疾病和/或病况，通过这些化合物结合所述核受体，并涉及这些化合物的合成过程。

  公开号：

  US20140221659A1
• 作为产物：
  描述：

  3-溴苯乙烯 在 tris-(dibenzylideneacetone)dipalladium(0) 、 正丁基锂 、 三氟甲磺酸酐 、 水 、 4,5-双二苯基膦-9,9-二甲基氧杂蒽 、 sodium hydroxide 作用下， 以 四氢呋喃 、 乙醇 、 正己烷 、 1,2-二氯乙烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 11.0h， 生成 3-((1s,3s)-3-(2-chloro-4-((5-cyclopropyl-3-(2,6-dichlorophenyl)isoxazol-4-yl)methoxy)phenyl)-3-hydroxycyclobutyl)benzoic acid
  参考文献：
  名称：

  NOVEL FXR (NR1H4) BINDING AND ACTIVITY MODULATING COMPOUNDS

  摘要：

  本发明涉及结合NR1H4受体（FXR）并作为FXR激动剂的化合物。该发明还涉及利用这些化合物制备药物以治疗疾病和/或病况，通过这些化合物结合所述核受体，并涉及这些化合物的合成过程。

  公开号：

  US20140221659A1

文献信息

• NOVEL FXR (NR1H4) BINDING AND ACTIVITY MODULATING AZOLES
  申请人：Gilead Sciences, Inc.

  公开号：EP3246070A1

  公开（公告）日：2017-11-22

  The present invention relates to compounds which bind to the NR1 H4 receptor (FXR) and act as agonists of 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.

  本发明涉及与 NR1 H4 受体（FXR）结合并作为 FXR 激动剂的化合物。本发明还涉及化合物的用途，即通过所述化合物与所述核受体结合制备治疗疾病和/或病症的药物，以及所述化合物的合成工艺。
• FXR (NR1H4) binding and activity modulating compounds
  申请人：Gilead Sciences, Inc.

  公开号：US10220027B2

  公开（公告）日：2019-03-05

  The present invention relates to compounds which bind to the NR1H4 receptor (FXR) and act as agonists of 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.

  本发明涉及与 NR1H4 受体（FXR）结合并作为 FXR 激动剂的化合物。本发明还涉及化合物的用途，即通过所述化合物与所述核受体结合制备治疗疾病和/或病症的药物，以及所述化合物的合成工艺。
• Acyclic antivirals
  申请人：Janssen BioPharma, Inc.

  公开号：US10745427B2

  公开（公告）日：2020-08-18

  Disclosed herein are nucleotide analogs, methods of synthesizing nucleotide analogs and methods of treating diseases and/or conditions such as a HBV and/or HDV and/or HIV infection with one or more nucleotide analogs.

  本文公开了核苷酸类似物、合成核苷酸类似物的方法以及用一种或多种核苷酸类似物治疗疾病和/或病症（如 HBV 和/或 HDV 和/或 HIV 感染）的方法。
• Novel substituted isoxazole FXR agonists with cyclopropyl, hydroxycyclobutyl and hydroxyazetidinyl linkers: Understanding and improving key determinants of pharmacological properties
  作者：Olaf Kinzel、Christoph Steeneck、Thomas Schlüter、Andreas Schulz、Christian Gege、Ulrike Hahn、Eva Hambruch、Martin Hornberger、Adriana Spalwisz、Katharina Frick、Sanja Perović-Ottstadt、Ulrich Deuschle、Michael Burnet、Claus Kremoser

  DOI：10.1016/j.bmcl.2016.05.070

  日期：2016.8

  Several isoxazole-containing series of FXR agonists have been published over the last 15 years, subsequent to the prototypical amphiphilic 'hammerhead'-type structure that was originally laid out by GW4064, the first potent synthetic FXR agonist. A set of novel compounds where the hammerhead is connected to the terminal carboxylic acid-bearing aryl or heteroaryl moiety by either a cyclopropyl, a hydroxycyclobutyl or a hydroxyazetidinyl linker was synthesized in order to improve upon the ADME properties of such isoxazoles. The resulting compounds all demonstrated high potencies at the target receptor FXR but with considerable differences in their physicochemical and in vivo profiles. The structure-activity relationships for key chemical features that have a major impact on the in vivo pharmacology of this series are discussed. (C) 2016 Elsevier Ltd. All rights reserved.
• NOVEL FXR (NR1H4) MODULATING COMPOUNDS
  申请人：Gilead Sciences, Inc.

  公开号：EP2731676B1

  公开（公告）日：2016-02-03