3-(4-chlorophenyl)-2-methyl-5-(trifluoromethyl)quinoxaline | 1221265-58-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: 3-(4-chlorophenyl)-2-methyl-5-(trifluoromethyl)quinoxaline
• CAS: 1221265-58-2
• 化学式: C₁₆H₁₀ClF₃N₂
• 分子量: 322.717
• InChiKey: QAQIUHQUQIUXAK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  22
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  25.8
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  2,3-二氨基三氟甲苯 、 1-(4-氯苯基)-1,2-丙二酮 以 乙醇 为溶剂， 反应 1.0h， 以36%的产率得到2-(4-chlorophenyl)-3-methyl-5-(trifluoromethyl)quinoxaline
  参考文献：
  名称：

  Identification of Phenylsulfone-Substituted Quinoxaline (WYE-672) as a Tissue Selective Liver X-receptor (LXR) Agonist

  摘要：

  A series of phenyl sulfone substituted quinoxaline were prepared and the lead compound 13 (WYE-672) was shown to be a tissue selective LXR Agonist. Compound 13 demonstrated partial agonism for LXR beta in kidney HEK-293 cells but did not activate Gal4 LXR beta fusion proteins in huh-7 liver cells. Although 13 showed potent binding affinity to LXR beta (IC50 = 53 nM), it had little binding affinity for LXR alpha (IC50 > 1.0 mu M) and did not recruit any coactivator/corepressor peptides in the LXRa multiplex assay. However, compound 13 showed good agonism in THP-1 cells with respect to increasing ABCA1 gene expression and good potency on cholesterol efflux in THP-1 foam cells. In an eight-week lesion study in LDLR -/- mice, compound 13 showed reduction of aortic arch lesion progression and no plasma or hepatic triglyceride increase. These results suggest quinoxaline 13 may have an improved biological profile for potential use as a therapeutic agent.

  DOI：

  10.1021/jm100034x

文献信息

• Identification of Phenylsulfone-Substituted Quinoxaline (WYE-672) as a Tissue Selective Liver X-receptor (LXR) Agonist
  作者：Baihua Hu、Rayomand J. Unwalla、Igor Goljer、James W. Jetter、Elaine M. Quinet、Thomas J. Berrodin、Michael D. Basso、Irene B. Feingold、Annika Goos Nilsson、Anna Wilhelmsson、Mark J. Evans、Jay E. Wrobel

  DOI：10.1021/jm100034x

  日期：2010.4.22

  A series of phenyl sulfone substituted quinoxaline were prepared and the lead compound 13 (WYE-672) was shown to be a tissue selective LXR Agonist. Compound 13 demonstrated partial agonism for LXR beta in kidney HEK-293 cells but did not activate Gal4 LXR beta fusion proteins in huh-7 liver cells. Although 13 showed potent binding affinity to LXR beta (IC50 = 53 nM), it had little binding affinity for LXR alpha (IC50 > 1.0 mu M) and did not recruit any coactivator/corepressor peptides in the LXRa multiplex assay. However, compound 13 showed good agonism in THP-1 cells with respect to increasing ABCA1 gene expression and good potency on cholesterol efflux in THP-1 foam cells. In an eight-week lesion study in LDLR -/- mice, compound 13 showed reduction of aortic arch lesion progression and no plasma or hepatic triglyceride increase. These results suggest quinoxaline 13 may have an improved biological profile for potential use as a therapeutic agent.