rac-2-ethoxy-3-{1-[3-(5-methyl-2-phenyl-oxazol-4-yl)-propyl]-1H-indol-4-yl}-propionic acid

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: rac-2-ethoxy-3-{1-[3-(5-methyl-2-phenyl-oxazol-4-yl)-propyl]-1H-indol-4-yl}-propionic acid
• 英文别名: 2-ethoxy-3-(1-(3-(5-methyl-2-phenyloxazol-4-yl)propyl)-1H-indol-4-yl)propanoic acid；2-ethoxy-3-[1-[3-(5-methyl-2-phenyl-1,3-oxazol-4-yl)propyl]indol-4-yl]propanoic acid
• 化学式: C₂₆H₂₈N₂O₄
• 分子量: 432.519
• InChiKey: DKDATBYVPQYIRT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  32
• 可旋转键数：
  10
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  77.5
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  4-吲哚甲醛 在 palladium on activated charcoal 氢氧化钾 、 1,1,2,3-四甲基胍 、 氢气 作用下， 以 乙醇 、 二氯甲烷 、 二甲基亚砜 为溶剂， 22.0~40.0 ℃ 、101.33 kPa 条件下， 生成 rac-2-ethoxy-3-{1-[3-(5-methyl-2-phenyl-oxazol-4-yl)-propyl]-1H-indol-4-yl}-propionic acid
  参考文献：
  名称：

  Structure-based design of indole propionic acids as novel PPARα/γ co-agonists

  摘要：

  In the quest for novel PPARalpha/gamma co-agonists as putative drugs for the treatment of type 2 diabetes and dyslipidemia, we have used a structure-based design approach to identify propionic acids with a 1,5-disubstituted indole scaffold as potent PPARalpha/gamma activators. Compounds 13, 24, and 28 are examples of submicromolar dual agonists with different alpha/gamma EC50 ratios that are selective against the delta-isoform. Analysis of the X-ray complex structure of PPARgamma with the indole propionic acid 13 provides a rationalization for some of the observed SAR.

  DOI：

  10.1016/j.bmcl.2006.05.007

文献信息

• Indolyl derivatives
  申请人：——

  公开号：US20040106657A1

  公开（公告）日：2004-06-03

  The present invention provides compounds of formula I 1 as well as pharmaceutically acceptable salts and esters thereof, wherein R 1 to R 4 , A and n have the significance given in the specification. The compounds or their salts may be administered to a patient for treating non-insulin dependent diabetes mellitus.

  本发明提供了化合物I1的结构，以及其药用可接受的盐和酯，其中R1到R4，A和n在规范中给出。这些化合物或其盐可以用于治疗非胰岛素依赖型糖尿病。
• INDOLYL DERIVATIVES
  申请人：F.HOFFMANN-LA ROCHE AG

  公开号：EP1567523A1

  公开（公告）日：2005-08-31
• US7098228B2
  申请人：——

  公开号：US7098228B2

  公开（公告）日：2006-08-29
• [EN] INDOLYL DERIVATIVES<br/>[FR] DERIVES D'INDOLYLE
  申请人：HOFFMANN LA ROCHE

  公开号：WO2004048371A1

  公开（公告）日：2004-06-10

  Compounds of formula (I) as well as pharmaceutically acceptable salts and esters thereof, wherein R1 to R4, A and n have the significance given in claim 1 can be used in the form of pharmaceutical preparations.
• Structure-based design of indole propionic acids as novel PPARα/γ co-agonists
  作者：Bernd Kuhn、Hans Hilpert、Jörg Benz、Alfred Binggeli、Uwe Grether、Roland Humm、Hans Peter Märki、Markus Meyer、Peter Mohr

  DOI：10.1016/j.bmcl.2006.05.007

  日期：2006.8

  In the quest for novel PPARalpha/gamma co-agonists as putative drugs for the treatment of type 2 diabetes and dyslipidemia, we have used a structure-based design approach to identify propionic acids with a 1,5-disubstituted indole scaffold as potent PPARalpha/gamma activators. Compounds 13, 24, and 28 are examples of submicromolar dual agonists with different alpha/gamma EC50 ratios that are selective against the delta-isoform. Analysis of the X-ray complex structure of PPARgamma with the indole propionic acid 13 provides a rationalization for some of the observed SAR.