[4-({3-[3-benzoyl-8-(trifluoromethyl)quinolin-4-yl]phenoxy}methyl)phenyl]acetic acid | 854765-94-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: [4-({3-[3-benzoyl-8-(trifluoromethyl)quinolin-4-yl]phenoxy}methyl)phenyl]acetic acid
• 英文别名: 2-(4-{3-[3-Benzoyl-8-(trifluoromethyl)quinolin-4-yl]phenoxymethyl}phenyl)acetic acid；2-[4-[[3-[3-benzoyl-8-(trifluoromethyl)quinolin-4-yl]phenoxy]methyl]phenyl]acetic acid
• CAS: 854765-94-9
• 化学式: C₃₂H₂₂F₃NO₄
• 分子量: 541.526
• InChiKey: YAKODSHNCZYDPB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7
• 重原子数：
  40
• 可旋转键数：
  8
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  76.5
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  [4-({3-[3-benzoyl-8-(trifluoromethyl)quinolin-4-yl]phenoxy}methyl)phenyl]acetic acid 在 氢氧化钾 、 肼 作用下， 以 乙二醇 为溶剂， 反应 1.5h， 以26%的产率得到WAY-254011
  参考文献：
  名称：

  Discovery of Phenyl Acetic Acid Substituted Quinolines as Novel Liver X Receptor Agonists for the Treatment of Atherosclerosis

  摘要：

  A structure-based approach was used to optimize our new class of quinoline LXR modulators leading to phenyl acetic acid substituted quinolines 15 and 16. Both compounds displayed good binding affinity for LXR beta and LXR alpha and were potent activators in LBD transactivation assays. The compounds also increased expression of ABCA1 and stimulated cholesterol efflux in THP-1 cells. Quinoline 16 showed good oral bioavailability and in vivo efficacy in a LDLr knockout mouse model for lesions.

  DOI：

  10.1021/jm0609566
• 作为产物：
  描述：

  邻氨基三氟甲苯 在 四(三苯基膦)钯 sodium hydroxide 、 potassium phosphate 、 potassium carbonate 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 乙醚 、 N,N-二甲基甲酰胺 、 丙酮 、 甲苯 为溶剂， 反应 43.0h， 生成 [4-({3-[3-benzoyl-8-(trifluoromethyl)quinolin-4-yl]phenoxy}methyl)phenyl]acetic acid
  参考文献：
  名称：

  Discovery of Phenyl Acetic Acid Substituted Quinolines as Novel Liver X Receptor Agonists for the Treatment of Atherosclerosis

  摘要：

  A structure-based approach was used to optimize our new class of quinoline LXR modulators leading to phenyl acetic acid substituted quinolines 15 and 16. Both compounds displayed good binding affinity for LXR beta and LXR alpha and were potent activators in LBD transactivation assays. The compounds also increased expression of ABCA1 and stimulated cholesterol efflux in THP-1 cells. Quinoline 16 showed good oral bioavailability and in vivo efficacy in a LDLr knockout mouse model for lesions.

  DOI：

  10.1021/jm0609566

文献信息

• Quinolines useful in treating cardiovascular disease
  申请人：Collini D. Michael

  公开号：US20050131014A1

  公开（公告）日：2005-06-16

  This invention provides compounds of formula I that are useful in the treatment or inhibition of LXR mediated diseases.

  本发明提供了式I化合物的用途，它们在治疗或抑制LXR介导的疾病中是有用的。
• Carboxylic acid based quinolines as liver X receptor modulators that have LXRβ receptor binding selectivity
  作者：Baihua Hu、Elaine Quinet、Rayomand Unwalla、Mike Collini、James Jetter、Rebecca Dooley、Diane Andraka、Lisa Nogle、Dawn Savio、Anita Halpern、Annika Goos-Nilsson、Anna Wilhelmsson、Ponnal Nambi、Jay Wrobel

  DOI：10.1016/j.bmcl.2007.11.013

  日期：2008.1

  A series of potent and binding selective LXR beta agonists was developed using the previously reported non-selective LXR ligand WAY-254011 as a structural template. With the aid of molecular modeling, it was found that 2,3-diMe-Ph, 2,5-diMe-Ph, and naphthalene substituted quinoline acetic acids (such as quinoline 33, 37, and 38) showed selectivity for LXR beta over LXR alpha in binding assays. (C) 2007 Elsevier Ltd. All rights reserved.
• QUINOLINES USEFUL IN TREATING CARDIOVASCULAR DISEASE
  申请人：Wyeth, A Corporation of the State of Delaware

  公开号：EP1692111A2

  公开（公告）日：2006-08-23
• JP2007516258A
  申请人：——

  公开号：JP2007516258A

  公开（公告）日：2007-06-21
• US7576215B2
  申请人：——

  公开号：US7576215B2

  公开（公告）日：2009-08-18