3-(4-chlorophenyl)-7-(trifluoromethyl)-1H-indazole | 1085267-46-4

• 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-(4-chlorophenyl)-7-(trifluoromethyl)-1H-indazole
• 英文别名: 3-(4-chlorophenyl)-7-(trifluoromethyl)-2H-indazole
• CAS: 1085267-46-4
• 化学式: C₁₄H₈ClF₃N₂
• 分子量: 296.679
• InChiKey: VYTPUDNIDZEDJB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  20
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  28.7
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-(4-chlorophenyl)-7-(trifluoromethyl)-1H-indazole 、 2-氯苄溴 以 N,N-二甲基甲酰胺 为溶剂， 以27%的产率得到2-(2-chlorobenzyl)-3-(4-chlorophenyl)-7-(trifluoromethyl)-2H-indazole
  参考文献：
  名称：

  Indazole-Based Liver X Receptor (LXR) Modulators with Maintained Atherosclerotic Lesion Reduction Activity but Diminished Stimulation of Hepatic Triglyceride Synthesis

  摘要：

  A series of substituted 2-benzyl-3-aryl-7-trifluoromethylindazoles were prepared as LXR modulators. These compounds were partial agonists in transactivation assays when compared to 1 (T0901317) and were slightly weaker with respect to potency and efficacy on LXR alpha than on LXR beta. Lead compounds in this series 12 (WAY-252623) and 13 (WAY-214950) showed less lipid accumulation in HepG2 cells than potent full agonists 1 and 3 (WAY-254011) but were comparable in efficacy to 1 and 3 with respect to cholesterol efflux in THP-1 foam cells, albeit weaker in potency. Compound 13 reduced aortic lesion area in LDLR knockout mice equivalently to 3 or positive control 2 (GW3965). In a 7-day hamster model, compound 13 showed a lesser propensity for plasma TG elevation than 3, when the compounds were compared at doses in which they elevated ABCA1 and ABCG1 gene expression in duodenum and liver at equal levels. In contrast to results previously published for 2, the lack of TG effect of 13 correlated with its inability to increase liver fatty acid synthase (FAS) gene expression, which was up-regulated 4-fold by 3. These results suggest indazoles such as 13 may have an improved profile for potential use as a therapeutic agent.

  DOI：

  10.1021/jm800799q
• 作为产物：
  描述：

  (2-fluoro-3-(trifluoromethyl)phenyl)(4-chlorophenyl)methanone 在 4-二甲氨基吡啶 、 一水合肼 作用下， 以 吡啶 为溶剂， 以73%的产率得到3-(4-chlorophenyl)-7-(trifluoromethyl)-1H-indazole
  参考文献：
  名称：

  Indazole-Based Liver X Receptor (LXR) Modulators with Maintained Atherosclerotic Lesion Reduction Activity but Diminished Stimulation of Hepatic Triglyceride Synthesis

  摘要：

  A series of substituted 2-benzyl-3-aryl-7-trifluoromethylindazoles were prepared as LXR modulators. These compounds were partial agonists in transactivation assays when compared to 1 (T0901317) and were slightly weaker with respect to potency and efficacy on LXR alpha than on LXR beta. Lead compounds in this series 12 (WAY-252623) and 13 (WAY-214950) showed less lipid accumulation in HepG2 cells than potent full agonists 1 and 3 (WAY-254011) but were comparable in efficacy to 1 and 3 with respect to cholesterol efflux in THP-1 foam cells, albeit weaker in potency. Compound 13 reduced aortic lesion area in LDLR knockout mice equivalently to 3 or positive control 2 (GW3965). In a 7-day hamster model, compound 13 showed a lesser propensity for plasma TG elevation than 3, when the compounds were compared at doses in which they elevated ABCA1 and ABCG1 gene expression in duodenum and liver at equal levels. In contrast to results previously published for 2, the lack of TG effect of 13 correlated with its inability to increase liver fatty acid synthase (FAS) gene expression, which was up-regulated 4-fold by 3. These results suggest indazoles such as 13 may have an improved profile for potential use as a therapeutic agent.

  DOI：

  10.1021/jm800799q

文献信息

• Indazole-Based Liver X Receptor (LXR) Modulators with Maintained Atherosclerotic Lesion Reduction Activity but Diminished Stimulation of Hepatic Triglyceride Synthesis
  作者：Jay Wrobel、Robert Steffan、S. Marc Bowen、Ronald Magolda、Edward Matelan、Rayomand Unwalla、Michael Basso、Valerie Clerin、Stephen J. Gardell、Ponnal Nambi、Elaine Quinet、Jason I. Reminick、George P. Vlasuk、Shuguang Wang、Irene Feingold、Christine Huselton、Tomas Bonn、Mathias Farnegardh、Tomas Hansson、Annika Goos Nilsson、Anna Wilhelmsson、Edouard Zamaratski、Mark J. Evans

  DOI：10.1021/jm800799q

  日期：2008.11.27

  A series of substituted 2-benzyl-3-aryl-7-trifluoromethylindazoles were prepared as LXR modulators. These compounds were partial agonists in transactivation assays when compared to 1 (T0901317) and were slightly weaker with respect to potency and efficacy on LXR alpha than on LXR beta. Lead compounds in this series 12 (WAY-252623) and 13 (WAY-214950) showed less lipid accumulation in HepG2 cells than potent full agonists 1 and 3 (WAY-254011) but were comparable in efficacy to 1 and 3 with respect to cholesterol efflux in THP-1 foam cells, albeit weaker in potency. Compound 13 reduced aortic lesion area in LDLR knockout mice equivalently to 3 or positive control 2 (GW3965). In a 7-day hamster model, compound 13 showed a lesser propensity for plasma TG elevation than 3, when the compounds were compared at doses in which they elevated ABCA1 and ABCG1 gene expression in duodenum and liver at equal levels. In contrast to results previously published for 2, the lack of TG effect of 13 correlated with its inability to increase liver fatty acid synthase (FAS) gene expression, which was up-regulated 4-fold by 3. These results suggest indazoles such as 13 may have an improved profile for potential use as a therapeutic agent.