2-Methyl-2-phenoxypropanoic acid, 27 | 343321-98-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 2-Methyl-2-phenoxypropanoic acid, 27
• 英文别名: 2-methyl-2-[4-[[methyl-[4-methyl-2-[4-(trifluoromethyl)phenyl]-1,3-thiazole-5-carbonyl]amino]methyl]phenoxy]propanoic acid
• CAS: 343321-98-2
• 化学式: C₂₄H₂₃F₃N₂O₄S
• 分子量: 492.519
• InChiKey: LNPYUCKFDARPOI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  34
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  108
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  4-(三氟甲基)硫代苯甲酰胺 在 sodium hydroxide 、 氯化亚砜 、 sodium hydride 、 三乙胺 作用下， 以 乙醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 65.0h， 生成 2-Methyl-2-phenoxypropanoic acid, 27
  参考文献：
  名称：

  Substituted 2-[(4-Aminomethyl)phenoxy]-2-methylpropionic Acid PPARα Agonists. 1. Discovery of a Novel Series of Potent HDLc Raising Agents

  摘要：

  The peroxisome proliferator activated receptors PPAR alpha, PPAR gamma, and PPAR delta are ligand-activated transcription factors that play a key role in lipid homeostasis. The fibrates raise circulating levels of high-density lipoprotein cholesterol and lower levels of triglycerides in part through their activity as PPAR alpha agonists; however, the low potency and restricted selectivity of the fibrates may limit their efficacy, and it would be desirable to develop more potent and selective PPAR alpha agonists. Modification of the selective PPAR delta agonist 1 (GW501516) so as to incorporate the 2-aryl-2-methylpropionic acid group of the fibrates led to a marked shift in potency and selectivity toward PPAR alpha agonism. Optimization of the series gave 25a, which shows EC50 = 4 nM on PPAR alpha and at least 500-fold selectivity versus PPAR delta and PPAR gamma. Compound 25a (GW590735) has been progressed to clinical trials for the treatment of diseases of lipid imbalance.

  DOI：

  10.1021/jm058056x

文献信息

• SUBSTITUTED OXAZOLES AND THIAZOLES DERIVATIVES AS HPPAR ALPHA ACTIVATORS
  申请人：GLAXO GROUP LIMITED

  公开号：EP1244642B1

  公开（公告）日：2004-04-28
• US6518290B1
  申请人：——

  公开号：US6518290B1

  公开（公告）日：2003-02-11
• Substituted 2-[(4-Aminomethyl)phenoxy]-2-methylpropionic Acid PPARα Agonists. 1. Discovery of a Novel Series of Potent HDLc Raising Agents
  作者：Michael L. Sierra、Véronique Beneton、Anne-Bénédict Boullay、Thierry Boyer、Andrew G. Brewster、Frédéric Donche、Marie-Claire Forest、Marie-Hélène Fouchet、Françoise J. Gellibert、Didier A. Grillot、Millard H. Lambert、Alain Laroze、Christelle Le Grumelec、Jean Michel Linget、Valerie G. Montana、Van-Loc Nguyen、Edwige Nicodème、Vipul Patel、Annie Penfornis、Olivier Pineau、Danig Pohin、Florent Potvain、Géraldine Poulain、Cécile Bertho Ruault、Michael Saunders、Jérôme Toum、H. Eric Xu、Robert X. Xu、Pascal M. Pianetti

  DOI：10.1021/jm058056x

  日期：2007.2.1

  The peroxisome proliferator activated receptors PPAR alpha, PPAR gamma, and PPAR delta are ligand-activated transcription factors that play a key role in lipid homeostasis. The fibrates raise circulating levels of high-density lipoprotein cholesterol and lower levels of triglycerides in part through their activity as PPAR alpha agonists; however, the low potency and restricted selectivity of the fibrates may limit their efficacy, and it would be desirable to develop more potent and selective PPAR alpha agonists. Modification of the selective PPAR delta agonist 1 (GW501516) so as to incorporate the 2-aryl-2-methylpropionic acid group of the fibrates led to a marked shift in potency and selectivity toward PPAR alpha agonism. Optimization of the series gave 25a, which shows EC50 = 4 nM on PPAR alpha and at least 500-fold selectivity versus PPAR delta and PPAR gamma. Compound 25a (GW590735) has been progressed to clinical trials for the treatment of diseases of lipid imbalance.