N-((1-(3-methoxybenzyl)-3-(3-methoxyphenyl)-1H-pyrazol-4-yl)methyl)-4-methyl-3-(morpholinosulfonyl)aniline | 1609565-02-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: N-((1-(3-methoxybenzyl)-3-(3-methoxyphenyl)-1H-pyrazol-4-yl)methyl)-4-methyl-3-(morpholinosulfonyl)aniline
• 英文别名: N-[[3-(3-methoxyphenyl)-1-[(3-methoxyphenyl)methyl]pyrazol-4-yl]methyl]-4-methyl-3-morpholin-4-ylsulfonylaniline
• CAS: 1609565-02-7
• 化学式: C₃₀H₃₄N₄O₅S
• 分子量: 562.69
• InChiKey: TXZDXFGWOHQAMF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  40
• 可旋转键数：
  10
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  103
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  (3-甲氧基苯甲酰)乙酸乙酯 在 4-二甲氨基吡啶 、 硼烷四氢呋喃络合物 、 乙酸酐 、 caesium carbonate 、 一水合肼 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 potassium hydroxide 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 水 、 乙腈 为溶剂， 反应 61.5h， 生成 N-((1-(3-methoxybenzyl)-3-(3-methoxyphenyl)-1H-pyrazol-4-yl)methyl)-4-methyl-3-(morpholinosulfonyl)aniline
  参考文献：
  名称：

  Identification of trisubstituted-pyrazol carboxamide analogs as novel and potent antagonists of farnesoid X receptor

  摘要：

  Farnesoid X receptor (FXR, NRIH4) plays a major role in the control of cholesterol metabolism. This suggests that antagonizing the transcriptional activity of FXR is a potential means to treat cholestasis and related metabolic disorders. Here we describe the synthesis, biological evaluation, and structure-activity relationship (SAR) studies of trisubstituted-pyrazol carboxamides as novel and potent FXR antagonists. One of these novel FXR antagonists, 4j has an IC50 of 7.5 nM in an FXR binding assay and 468.5 nM in a cell-based FXR antagonistic assay. Compound 4j has no detectable FXR agonistic activity or cytotoxicity. Notably, 4j is the most potent FXR antagonist identified to date; it has a promising in vitro profile and could serve as an excellent chemical tool to elucidate the biological function of FXR. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2014.04.014

文献信息

• Farnesoid X receptor antagonists
  申请人：City of Hope

  公开号：US10611729B2

  公开（公告）日：2020-04-07

  Provided herein are Famesoid X receptor (FXR) antagonists having the structure of formula (I), and pharmaceutical compositions comprising the compound of formula (I) and a pharmaceutically acceptable excipient. Also provided are methods of antagonizing FXR, and methods of treating metabolic disease in a subject in need thereof, comprising administering an effective amount of the FXR antagonists of formula (I) to a subject.

  本文提供了具有式(I)结构的类雌激素X受体(FXR)拮抗剂，以及包含式(I)化合物和药学上可接受的赋形剂的药物组合物。还提供了拮抗 FXR 的方法，以及治疗有需要的受试者的代谢疾病的方法，包括向受试者施用有效量的式 (I) 的 FXR 拮抗剂。
• [EN] FARNESOID X RECEPTOR ANTAGONISTS<br/>[FR] ANTAGONISTES DU RÉCEPTEUR X DE FARNÉSOÏDE
  申请人：HOPE CITY

  公开号：WO2015116856A3

  公开（公告）日：2015-11-05
• FARNESOID X RECEPTOR ANTAGONISTS
  申请人：City of Hope

  公开号：US20170008851A1

  公开（公告）日：2017-01-12

  Provided herein are Farnesoid X receptor (FXR) antagonists having the structure of formula (I), and pharmaceutical compositions comprising the compound of formula (I) and a pharmaceutically acceptable excipient. Also provided are methods of antagonizing FXR, and methods of treating metabolic disease in a subject in need thereof, comprising administering an effective amount of the FXR antagonists of formula (I) to a subject.
• US9944605B2
  申请人：——

  公开号：US9944605B2

  公开（公告）日：2018-04-17