1-(4-fluorophenyl)-3-p-tolyl-1H-pyrazole-4-carboxylic acid | 956779-12-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 1-(4-fluorophenyl)-3-p-tolyl-1H-pyrazole-4-carboxylic acid
• 英文别名: 1-(4-fluorophenyl)-3-(4-methylphenyl)-1H-pyrazole-4-carboxylic acid；1-(4-fluorophenyl)-3-(4-methylphenyl)pyrazole-4-carboxylic acid
• CAS: 956779-12-7
• 化学式: C₁₇H₁₃FN₂O₂
• mdl: MFCD06357437
• 分子量: 296.301
• InChiKey: SLCBEWVMMQNFTN-UHFFFAOYSA-N

物化性质

• 沸点：
  454.4±40.0 °C(Predicted)
• 密度：
  1.27±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.058
• 拓扑面积：
  55.1
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-甲基-3-(吗啉-4-磺酰基)-苯胺 、 1-(4-fluorophenyl)-3-p-tolyl-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 13.0h， 以26%的产率得到1-(4-fluorophenyl)-N-(4-methyl-3-(morpholinosulfonyl)phenyl)-3-p-tolyl-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：

  (E)-1-(4-fluorophenyl)-2-(1-p-tolylethylidene)hydrazine 在 Jones reagent 、 三氯氧磷 作用下， 以 丙酮 为溶剂， 反应 18.17h， 生成 1-(4-fluorophenyl)-3-p-tolyl-1H-pyrazole-4-carboxylic acid
  参考文献：
  名称：

  [EN] FARNESOID X RECEPTOR ANTAGONISTS
  [FR] ANTAGONISTES DU RÉCEPTEUR X DE FARNÉSOÏDE

  摘要：

  公开号：

  WO2015116856A3

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
• Identification of trisubstituted-pyrazol carboxamide analogs as novel and potent antagonists of farnesoid X receptor
  作者：Donna D. Yu、Wenwei Lin、Barry M. Forman、Taosheng Chen

  DOI：10.1016/j.bmc.2014.04.014

  日期：2014.6

  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.