3-(p-tolyl)-1-(3-(trifluoromethyl)phenyl)-1H-pyrazole-4-carboxylic acid | 1609564-64-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 3-(p-tolyl)-1-(3-(trifluoromethyl)phenyl)-1H-pyrazole-4-carboxylic acid
• 英文别名: 3-(4-Methylphenyl)-1-[3-(trifluoromethyl)phenyl]pyrazole-4-carboxylic acid
• CAS: 1609564-64-8
• 化学式: C₁₈H₁₃F₃N₂O₂
• 分子量: 346.309
• InChiKey: SUHKYOVXYDNBOT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  25
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  55.1
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  4-甲基-3-(吗啉-4-磺酰基)-苯胺 、 3-(p-tolyl)-1-(3-(trifluoromethyl)phenyl)-1H-pyrazole-4-carboxylic acid 在 1-羟基苯并三唑 、 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， 反应 17.0h， 以31%的产率得到N-(4-methyl-3-(morpholinosulfonyl)phenyl)-3-(p-tolyl)-1-(3-(trifluoromethyl) phenyl)-1H-pyrazole-4-carboxamide
  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
• 作为产物：
  描述：

  3-p-tolyl-1-(3-(trifluoromethyl)phenyl)-1H-pyrazole-4-carbaldehyde 在 Jones reagent 作用下， 以 丙酮 为溶剂， 以98%的产率得到3-(p-tolyl)-1-(3-(trifluoromethyl)phenyl)-1H-pyrazole-4-carboxylic acid
  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

• [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