2-methyl-2-(1-{3-[1-propyl-6-(pyridine-4-carbonyl)-naphthalen-2-yloxy]-propyl}-1H-indol-5-yloxy)-propionic acid | 1143573-14-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 2-methyl-2-(1-{3-[1-propyl-6-(pyridine-4-carbonyl)-naphthalen-2-yloxy]-propyl}-1H-indol-5-yloxy)-propionic acid
• 英文别名: 2-methyl-2-[1-[3-[1-propyl-6-(pyridine-4-carbonyl)naphthalen-2-yl]oxypropyl]indol-5-yl]oxypropanoic acid
• CAS: 1143573-14-1
• 化学式: C₃₄H₃₄N₂O₅
• 分子量: 550.654
• InChiKey: ASRAVNHIRAGAPY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7
• 重原子数：
  41
• 可旋转键数：
  12
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  90.6
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  ethyl 2-[1-(3-chloropropyl)-1H-indol-5-yloxy]-2-methylpropionate 、 (6-hydroxy-5-propyl-naphthalen-2-yl)-pyridin-4-yl-methanone 在 potassium carbonate 、 potassium iodide 、 lithium hydroxide 作用下， 以 N,N-二甲基甲酰胺 、 甲醇 、 水 为溶剂， 反应 4.0h， 以78%的产率得到2-methyl-2-(1-{3-[1-propyl-6-(pyridine-4-carbonyl)-naphthalen-2-yloxy]-propyl}-1H-indol-5-yloxy)-propionic acid
  参考文献：
  名称：

  Design and Structural Analysis of Novel Pharmacophores for Potent and Selective Peroxisome Proliferator-activated Receptor γ Agonists

  摘要：

  Utilizing medicinal chemistry design strategies such as benzo splitting and ring expansion, we converted PPARalpha/gamma dual agonist 1 to selective PPARgamma agonists 19 and 20. Compounds 19 and 20 were 2- to 4-fold better than rosiglitazone at PPARgamma receptor, with 80- to 100-fold PPARgamma selectivity over PPARalpha receptor. X-ray cocrystal studies in PPARgamma and modeling studies in PPARalpha give molecular insights for the improved PPARgamma potency and selectivity for 19 when compared to 1.

  DOI：

  10.1021/jm801594x

文献信息

• Design and Structural Analysis of Novel Pharmacophores for Potent and Selective Peroxisome Proliferator-activated Receptor γ Agonists
  作者：Chia-Hui Lin、Yi-Hui Peng、Mohane Selvaraj Coumar、Santhosh Kumar Chittimalla、Chun-Chen Liao、Ping-Chiang Lyn、Chin-Chieh Huang、Tzu-Wen Lien、Wen-Hsing Lin、John T.-A. Hsu、Jai-Hong Cheng、Xin Chen、Jian-Sung Wu、Yu-Sheng Chao、Hwei-Jen Lee、Chiun-Gung Juo、Su-Ying Wu、Hsing-Pang Hsieh

  DOI：10.1021/jm801594x

  日期：2009.4.23

  Utilizing medicinal chemistry design strategies such as benzo splitting and ring expansion, we converted PPARalpha/gamma dual agonist 1 to selective PPARgamma agonists 19 and 20. Compounds 19 and 20 were 2- to 4-fold better than rosiglitazone at PPARgamma receptor, with 80- to 100-fold PPARgamma selectivity over PPARalpha receptor. X-ray cocrystal studies in PPARgamma and modeling studies in PPARalpha give molecular insights for the improved PPARgamma potency and selectivity for 19 when compared to 1.