2-[[4-[2-[(5-ethyl-2-pyrimidinyl)[[4-[(trifluoromethyl)oxy]phenyl]methyl]amino]-1,1-dimethylethyl]phenyl]oxy]-2-methylpropanoic acid

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 石蒜科生物碱
• 英文名称: 2-[[4-[2-[(5-ethyl-2-pyrimidinyl)[[4-[(trifluoromethyl)oxy]phenyl]methyl]amino]-1,1-dimethylethyl]phenyl]oxy]-2-methylpropanoic acid
• 英文别名: GW693085；2-[4-(2-{(5-ethylpyrimidin-2-yl)[4-(trifluoromethoxy)benzyl]amino}-1,1-dimethylethyl)phenoxy]-2-methylpropanoic acid；2-[4-[1-[(5-Ethylpyrimidin-2-yl)-[[4-(trifluoromethoxy)phenyl]methyl]amino]-2-methylpropan-2-yl]phenoxy]-2-methylpropanoic acid
• 化学式: C₂₈H₃₂F₃N₃O₄
• 分子量: 531.575
• InChiKey: PYPLHUGODGTUGK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.1
• 重原子数：
  38
• 可旋转键数：
  11
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  84.8
• 氢给体数：
  1
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  4-{2-[(5-ethyl-2-pyrimidinyl)({4-[(trifluoromethyl)oxy]phenyl}methyl)amino]-1,1-dimethylethyl}phenol 、 三氯叔丁醇 在 sodium hydroxide 作用下， 以 水 、 丙酮 为溶剂， 反应 3.86h， 以81%的产率得到2-[[4-[2-[(5-ethyl-2-pyrimidinyl)[[4-[(trifluoromethyl)oxy]phenyl]methyl]amino]-1,1-dimethylethyl]phenyl]oxy]-2-methylpropanoic acid
  参考文献：
  名称：

  Effects of Various Bases on Acid-Catalyzed Amination of 2-Chloro-5-ethylpyrimidine: Synthesis of PPARpan Agonist GW693085

  摘要：

  A unique buffering effect of various bases, i-Pr2NEt and CaCO3 in particular, was observed for the acid-catalyzed chloro displacement of 2-chloro-5-ethylpyrimidine with a 2-methyl-2-phenylpropanamine. The use of the carefully chosen bases was essential for the progression of the chloro displacement as well as the stability of the product in the presence of HCl formed. Research work leading to an efficient synthesis of PPARpan agonist GW693085 is described, featuring highly selective sequential N- and O-alkylations.

  DOI：

  10.1021/jo100562s

文献信息

• [EN] HPPARS ACTIVATORS<br/>[FR] ACTIVATEURS DE HPPARS
  申请人：SMITHKLINE BEECHAM CORP

  公开号：WO2003074495A1

  公开（公告）日：2003-09-12

  Compounds of formula (1) or a pharmaceutically acceptable salt, solvate, acid isostere, or hydrolyzable ester thereof, are disclosed. Methods of making and using the compounds are also disclosed. In particular methods for treating diseases or conditions associated with one or more of human PPAR alpha, gamma, or delta ('hPPARs') comprising administration of a therapeutically effective amount of a compound of formula (1), are disclosed.

  公式（1）的化合物或其药学上可接受的盐、溶剂合物、酸异构体或可水解酯已被披露。还披露了制备和使用这些化合物的方法。具体披露了用于治疗与人类PPARα、γ或δ（'hPPARs'）中的一个或多个相关疾病或症状的方法，包括给予公式（1）的化合物的治疗有效量。
• Hppars activators
  申请人：Cadilla Rodolfo

  公开号：US20050137212A1

  公开（公告）日：2005-06-23

  Compounds of formula (1) or a pharmaceutically acceptable salt, solvate, acid isostere, or hydrolyzable ester thereof, are disclosed. Methods of making and using the compounds are also disclosed. In particular methods for treating diseases or conditions associated with one or more of human PPAR alpha, gamma, or delta (“hPPARs”) comprising administration of a therapeutically effective amount of a compound of formula (1), are disclosed.

  本发明揭示了化学式（1）或其药学上可接受的盐、溶剂化物、酸同位素或可水解酯的化合物。本发明还揭示了制备和使用这些化合物的方法。特别是揭示了治疗与人类PPAR alpha、gamma或delta（“hPPARs”）中的一个或多个相关的疾病或病状的方法，包括给予化学式（1）的化合物的治疗有效量。
• HPPARS ACTIVATORS
  申请人：SMITHKLINE BEECHAM CORPORATION

  公开号：EP1480957A1

  公开（公告）日：2004-12-01
• US7319104B2
  申请人：——

  公开号：US7319104B2

  公开（公告）日：2008-01-15
• Effects of Various Bases on Acid-Catalyzed Amination of 2-Chloro-5-ethylpyrimidine: Synthesis of PPARpan Agonist GW693085
  作者：Bobby N. Glover、Lynda A. Jones、Byron, S. Johnson、Alan Millar、Martin H. Osterhout、Shiping Xie

  DOI：10.1021/jo100562s

  日期：2010.6.4

  A unique buffering effect of various bases, i-Pr2NEt and CaCO3 in particular, was observed for the acid-catalyzed chloro displacement of 2-chloro-5-ethylpyrimidine with a 2-methyl-2-phenylpropanamine. The use of the carefully chosen bases was essential for the progression of the chloro displacement as well as the stability of the product in the presence of HCl formed. Research work leading to an efficient synthesis of PPARpan agonist GW693085 is described, featuring highly selective sequential N- and O-alkylations.