rac-3-{1-[2-(3,5-dichloro-phenyl)-5-methyl-oxazol-4-ylmethyl]-1H-indol-5-yl}-2-ethoxy-propionic acid | 671216-01-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: rac-3-{1-[2-(3,5-dichloro-phenyl)-5-methyl-oxazol-4-ylmethyl]-1H-indol-5-yl}-2-ethoxy-propionic acid
• 英文别名: 3-(1-((2-(3,5-dichlorophenyl)-5-methyloxazol-4-yl)methyl)-1H-indol-5-yl)-2-ethoxypropanoic acid；3-[1-[[2-(3,5-dichlorophenyl)-5-methyl-1,3-oxazol-4-yl]methyl]indol-5-yl]-2-ethoxypropanoic acid
• CAS: 671216-01-6
• 化学式: C₂₄H₂₂Cl₂N₂O₄
• 分子量: 473.356
• InChiKey: RQMKNZHMAWCBJL-UHFFFAOYSA-N

物化性质

• 沸点：
  692.1±65.0 °C(Predicted)
• 密度：
  1.37±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.5
• 重原子数：
  32
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.25
• 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：

  5-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， 反应 42.0h， 生成 rac-3-{1-[2-(3,5-dichloro-phenyl)-5-methyl-oxazol-4-ylmethyl]-1H-indol-5-yl}-2-ethoxy-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：US20040053979A1

  公开（公告）日：2004-03-18

  Compounds of formula I are provided 1 as well as pharmaceutically acceptable salts and esters thereof, wherein R 1 to R 8 , A, A 1 and n have the significance indicated in the specification.

  提供了式I的化合物，以及其药用可接受的盐和酯，其中R1至R8，A，A1和n具有规范中指示的含义。
• N-SUBSTITUTED-1H-INDOL-5-PROPIONIC ACID COMPOUNDS AS PPAR AGONISTS USEFUL FOR THE TREATMENT OF DIABETES
  申请人：F. Hoffmann-La Roche AG

  公开号：EP1539746A1

  公开（公告）日：2005-06-15
• US6890947B2
  申请人：——

  公开号：US6890947B2

  公开（公告）日：2005-05-10
• [EN] N-SUBSTITUTED-1H-INDOL-5-PROPIONIC ACID COMPOUNDS AS PPAR AGONISTS USEFUL FOR THE TREATMENT OF DIABETES<br/>[FR] COMPOSES D'ACIDE 1H-INDOL-5-PROPIONIQUE A SUBSTITUTION N EN TANT QU'AGONISTES DE PPAR UTILES DANS LE TRAITEMENT DU DIABETE
  申请人：HOFFMANN LA ROCHE

  公开号：WO2004024726A1

  公开（公告）日：2004-03-25

  Compounds of formula (I), as well as pharmaceutically acceptable salts and esters thereof, wherein R1 to R8, A, A1 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.