4-[3-甲基-5-(三氟甲基)喹喔啉-2-基]苯基三氟甲磺酸酯 | 1221265-53-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 中文名称: 4-[3-甲基-5-(三氟甲基)喹喔啉-2-基]苯基三氟甲磺酸酯
• 英文名称: 4-[3-methyl-5-(trifluoromethyl)quinoxalin-2-yl]phenyl trifluoromethanesulfonate
• 英文别名: [4-[3-methyl-5-(trifluoromethyl)quinoxalin-2-yl]phenyl] trifluoromethanesulfonate
• CAS: 1221265-53-7
• 化学式: C₁₇H₁₀F₆N₂O₃S
• 分子量: 436.334
• InChiKey: RSGRTMVJNJBPHC-UHFFFAOYSA-N

物化性质

• 沸点：
  447.3±45.0 °C(Predicted)
• 密度：
  1.523±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  29
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  77.5
• 氢给体数：
  0
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  3-乙砜基苯硼酸 、 4-[3-甲基-5-(三氟甲基)喹喔啉-2-基]苯基三氟甲磺酸酯 在 potassium phosphate 、 四(三苯基膦)钯 作用下， 以 1,4-二氧六环 为溶剂， 反应 1.0h， 以75%的产率得到2-[3'-(ethylsulfonyl)biphenyl-4-yl]-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
• 作为产物：
  描述：

  N-苯基双(三氟甲烷磺酰)亚胺 、 4-[3-methyl-5-(trifluoromethyl)-quinoxalin-2-yl]phenol 在 potassium tert-butylate 作用下， 以 四氢呋喃 为溶剂， 以65%的产率得到4-[3-甲基-5-(三氟甲基)喹喔啉-2-基]苯基三氟甲磺酸酯
  参考文献：
  名称：

  QUINOXALINE-BASED LXR MODULATORS

  摘要：

  公开了基于喹诺克的Liver X受体（LXRs）调节剂及相关方法。这些调节剂包括以下式（I）的化合物： 其中： L1和L2分别独立为键，-O-或-NH-； R2是C6-C10的芳基或杂芳基，包括5-10个原子，每个原子（i）带有1个R9基团，和（ii）可选地带有1-4个Re基团； R4和R5分别独立为（i）氢；（ii）卤素；或（iii）C1-C6的烷基或C1-C6的卤代烷基，每个都可选地带有1-3个Ra基团； 以及R1、R3、R6、R9、Ra和Re都在此定义。 一般来说，这些化合物可用于治疗或预防一个或多个由LXRs介导的疾病、失调、状况或症状。

  公开号：

  US20100120778A1

文献信息

• QUINOXALINE-BASED LXR MODULATORS
  申请人：Hu Baihua

  公开号：US20100120778A1

  公开（公告）日：2010-05-13

  Disclosed are quinoxaline-based modulators of Liver X receptors (LXRs) and related methods. The modulators include compounds of formula (I): wherein: each of L 1 and L 2 is, independently, a bond, —O— or —NH—; R 2 is C 6 -C 10 aryl or heteroaryl including 5-10 atoms, each of which is (i) substituted with 1 R 9 , and (ii) optionally further substituted with from 1-4 R e ; and each of R 4 and R 5 is, independently (i) hydrogen; or (ii) halo; or (iii) C 1 -C 6 alkyl or C 1 -C 6 haloalkyl, each of which is optionally substituted with from 1-3 R a ; and R 1 , R 3 , R 6 , R 9 , R a and R e are defined herein. In general, these compounds can be used for treating or preventing one or more diseases, disorders, conditions or symptoms mediated by LXRs.

  公开了基于喹诺克的Liver X受体（LXRs）调节剂及相关方法。这些调节剂包括以下式（I）的化合物： 其中： L1和L2分别独立为键，-O-或-NH-； R2是C6-C10的芳基或杂芳基，包括5-10个原子，每个原子（i）带有1个R9基团，和（ii）可选地带有1-4个Re基团； R4和R5分别独立为（i）氢；（ii）卤素；或（iii）C1-C6的烷基或C1-C6的卤代烷基，每个都可选地带有1-3个Ra基团； 以及R1、R3、R6、R9、Ra和Re都在此定义。 一般来说，这些化合物可用于治疗或预防一个或多个由LXRs介导的疾病、失调、状况或症状。
• [EN] QUINOXALINE-BASED LXR MODULATORS<br/>[FR] MODULATEURS DE LXR À BASE DE QUINOXALINE
  申请人：WYETH LLC

  公开号：WO2010054229A1

  公开（公告）日：2010-05-14

  Disclosed are quinoxaline-based modulators of Liver X receptors (LXRs) and related methods. The modulators include compounds of formula (I): wherein: each of L1 and L2 is, independently, a bond, -O- or -NH-; R2 is C6-C10 aryl or heteroaryl including 5-10 ring atoms, each of which is (i) substituted with 1 R9, and (ii) optionally further substituted with from 1-4 Re; and each of R4 and R5 is, independently (i) hydrogen; or (ii) halo; or (iii) C1-C6 alkyl or C1-C6 haloalkyl, each of which is optionally substituted with from 1-3 Ra; and R1, R3, R6, R9, Ra and Re are defined herein. In general, these compounds can be used for treating or preventing one or more diseases, disorders, conditions or symptoms mediated by LXRs.

  本发明涉及基于喹哚醌的肝X受体（LXR）调节剂及相关方法。这些调节剂包括式（I）的化合物：其中：L1和L2中的每一个独立地是一个键，-O-或-NH-；R2是C6-C10芳基或杂环芳基，包括5-10个环原子，每个原子（i）被1个R9取代，并且（ii）可以进一步选择地被1-4个Re取代；R4和R5中的每一个独立地是（i）氢；或（ii）卤素；或（iii）C1-C6烷基或C1-C6卤代烷基，每一个取代基可以选择地被1-3个Ra取代；R1、R3、R6、R9、Ra和Re在此定义。一般来说，这些化合物可用于治疗或预防LXR介导的一种或多种疾病、障碍、症状或条件。
• 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.