(2-chloro-4-((3-(2,6-dichlorophenyl)-5-isopropylisoxazol-4-yl)methoxy)phenyl)methanol | 700835-89-8

• 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: (2-chloro-4-((3-(2,6-dichlorophenyl)-5-isopropylisoxazol-4-yl)methoxy)phenyl)methanol
• 英文别名: [2-Chloro-4-[[3-(2,6-dichlorophenyl)-5-propan-2-yl-1,2-oxazol-4-yl]methoxy]phenyl]methanol
• CAS: 700835-89-8
• 化学式: C₂₀H₁₈Cl₃NO₃
• 分子量: 426.727
• InChiKey: OHGIAMLQWBUWRN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.7
• 重原子数：
  27
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  55.5
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (2-chloro-4-((3-(2,6-dichlorophenyl)-5-isopropylisoxazol-4-yl)methoxy)phenyl)methanol 在 氯化亚砜 作用下， 以 二氯甲烷 为溶剂， 反应 2.5h， 以100%的产率得到4-{[3-chloro-4-(chloromethyl)phenoxy]methyl}-3-(2,6-dichlorophenyl)-5-isopropylisoxazole
  参考文献：
  名称：

  [EN] FARNESOID X RECEPTOR AGONISTS
  [FR] AGONISTES DE RECEPTEUR FARNESOIDE X

  摘要：

  本发明涉及一种具有以下式子(I)的化合物，用作FXR的激动剂：其中，所有变量均如本文所定义，并且涉及制备该化合物的制药组合物、使用方法和制备过程。

  公开号：

  WO2004048349A1
• 作为产物：
  描述：

  [3-(2,6-二氯苯基)-5-异丙基异恶唑-4-基]甲醇 在 偶氮二甲酸二异丙酯 、 二异丁基氢化铝 、 三苯基膦 作用下， 以 四氢呋喃 、 二氯甲烷 、 甲苯 为溶剂， 反应 28.0h， 生成 (2-chloro-4-((3-(2,6-dichlorophenyl)-5-isopropylisoxazol-4-yl)methoxy)phenyl)methanol
  参考文献：
  名称：

  Design and Structural Optimization of Dual FXR/PPARδ Activators

  摘要：

  Nonalcoholic steatohepatitis (NASH) is considered as severe hepatic manifestation of the metabolic syndrome and has alarming global prevalence. The ligand-activated transcription factors farnesoid X receptor (FXR) and peroxisome proliferator-activated receptor (PPAR) delta have been validated as molecular targets to counter NASH. To achieve robust therapeutic efficacy in this multifactorial pathology, combined peripheral PPAR delta-mediated activity and hepatic effects of FXR activation appear as a promising multitarget approach. We have designed a minimal dual FXR/PPAR delta activator scaffold by rational fusion of pharmacophores derived from selective agonists. Our dual agonist lead compound exhibited weak agonism on FXR and PPAR delta and was structurally refined to a potent and balanced FXR/PPAR delta activator in a computer-aided fashion. The resulting dual FXR/PPAR delta modulator comprises high selectivity over related nuclear receptors and activates the two target transcription factors in native cellular settings.

  DOI：

  10.1021/acs.jmedchem.0c00618

文献信息

• Farnesoid x receptor agonists
  申请人：Boggs D Sharon

  公开号：US20060258725A1

  公开（公告）日：2006-11-16

  The invention relates to a compound of formula (I): wherein all variables are as defined herein and to pharmaceutical compositions, methods of using, and processes for preparing the same.

  本发明涉及以下化合物的公式(I)：其中所有变量如定义所述，以及制备药物组合物，使用方法和过程。
• FARNESOID X RECEPTOR AGONISTS
  申请人：SmithKline Beecham Corporation

  公开号：EP1562915A1

  公开（公告）日：2005-08-17
• US7319109B2
  申请人：——

  公开号：US7319109B2

  公开（公告）日：2008-01-15
• Design and Structural Optimization of Dual FXR/PPARδ Activators
  作者：Simone Schierle、Sebastian Neumann、Pascal Heitel、Sabine Willems、Astrid Kaiser、Julius Pollinger、Daniel Merk

  DOI：10.1021/acs.jmedchem.0c00618

  日期：2020.8.13

  Nonalcoholic steatohepatitis (NASH) is considered as severe hepatic manifestation of the metabolic syndrome and has alarming global prevalence. The ligand-activated transcription factors farnesoid X receptor (FXR) and peroxisome proliferator-activated receptor (PPAR) delta have been validated as molecular targets to counter NASH. To achieve robust therapeutic efficacy in this multifactorial pathology, combined peripheral PPAR delta-mediated activity and hepatic effects of FXR activation appear as a promising multitarget approach. We have designed a minimal dual FXR/PPAR delta activator scaffold by rational fusion of pharmacophores derived from selective agonists. Our dual agonist lead compound exhibited weak agonism on FXR and PPAR delta and was structurally refined to a potent and balanced FXR/PPAR delta activator in a computer-aided fashion. The resulting dual FXR/PPAR delta modulator comprises high selectivity over related nuclear receptors and activates the two target transcription factors in native cellular settings.
• [EN] FARNESOID X RECEPTOR AGONISTS<br/>[FR] AGONISTES DE RECEPTEUR FARNESOIDE X
  申请人：SMITHKLINE BEECHAM CORP

  公开号：WO2004048349A1

  公开（公告）日：2004-06-10

  The invention relates to a compound of formula (I) useful as an agonist for FXR: wherein all variables are as defined herein and to pharmaceutical compositions, methods of using, and processes for preparing the same.

  本发明涉及一种具有以下式子(I)的化合物，用作FXR的激动剂：其中，所有变量均如本文所定义，并且涉及制备该化合物的制药组合物、使用方法和制备过程。