3-(4-fluorophenyl)-7-(trifluoromethyl)-1H-indazole | 875795-92-9

• 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-fluorophenyl)-7-(trifluoromethyl)-1H-indazole
• 英文别名: 3-(4-Fluoro-phenyl)-7-trifluoromethyl-1H-indazole；3-(4-fluorophenyl)-7-(trifluoromethyl)-2H-indazole
• CAS: 875795-92-9
• 化学式: C₁₄H₈F₄N₂
• 分子量: 280.225
• InChiKey: PWZVEJNQYWTSHA-UHFFFAOYSA-N

物化性质

• 沸点：
  400.8±40.0 °C(Predicted)
• 密度：
  1.414±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 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：
  5

反应信息

• 作为反应物：
  描述：

  3-(4-fluorophenyl)-7-(trifluoromethyl)-1H-indazole 、 2-氯苄溴 以 N,N-二甲基甲酰胺 为溶剂， 以37%的产率得到2-(2-chlorobenzyl)-3-(4-fluorophenyl)-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-fluorophenyl)methanone 在 4-二甲氨基吡啶 、 一水合肼 作用下， 以 吡啶 为溶剂， 以80%的产率得到3-(4-fluorophenyl)-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

• Indazoles useful in treating cardiovascular diseases
  申请人：Steffan J. Robert

  公开号：US20060030612A1

  公开（公告）日：2006-02-09

  This invention provides compounds of Formula (I) or (Ia): that are useful in the treatment or inhibition of LXR mediated diseases.

  这项发明提供了I式或Ia式化合物：它们可用于治疗或抑制LXR介导的疾病。
• Indazoles
  申请人：Wyeth

  公开号：US07592363B2

  公开（公告）日：2009-09-22

  This invention provides compounds of Formula (I) or (Ia): that are useful in the treatment or inhibition of LXR mediated diseases.

  该发明提供了公式(I)或(Ia)的化合物：它们在治疗或抑制LXR介导的疾病方面是有用的。
• 3-((hetero)aryl)-indazoles as Liver X receptor (LXR) and Th-1 inhibitors for the treatment of cardiovascular diseases
  申请人：Wyeth LLC

  公开号：EP2295429A1

  公开（公告）日：2011-03-16

  This invention provides compounds of Formula (Ia): wherein: R1 has various meanings including C1-6 alkyl, CN, CO2R5, C(O)R5, C2-6 alkenyl, C3-8 cycloalkenyl, C2-6 alkynyl, NR5R6, C(O)NR5R6, phenyl, thiophene, C1-3 alkoxy, halogen and S(O)kR5; R2 is heteroaryl, substituted with YD; or R2 is phenyl substituted with up to four substituents YD; R20 is H or C1-3 alkyl; and R4 is H, halogen, methyl or methoxy; and pharmaceutically acceptable salts thereof. The compounds and salts are useful in the treatment or inhibition of Liver X Receptor (LXR) mediated diseases.

  本发明提供了式 (Ia) 的化合物： 其中 R1具有各种含义，包括C1-6烷基、CN、CO2R5、C(O)R5、C2-6烯基、C3-8环烯基、C2-6炔基、NR5R6、C(O)NR5R6、苯基、噻吩、C1-3烷氧基、卤素和S(O)kR5； R2 是被 YD 取代的杂芳基；或 R2 是被最多四个 YD 取代基取代的苯基； R20 是 H 或 C1-3 烷基；以及 R4 是 H、卤素、甲基或甲氧基； 及其药学上可接受的盐类。 这些化合物和盐可用于治疗或抑制肝 X 受体（LXR）介导的疾病。
• J. Med. Chem. 2008, 51, 7161-7168
  作者：

  DOI：——

  日期：——
• INDAZOLES USEFUL IN TREATING CARDIOVASCULAR DISEASES
  申请人：Wyeth

  公开号：EP1773781A2

  公开（公告）日：2007-04-18