ethyl 2-methyl-2-{[4-({[(4-methyl-2-{4-[(methylsulfonyl)oxy]phenyl}-1,3-thiazol-5-yl)carbonyl]amino}methyl)phenyl]oxy}propanoate | 929693-91-4

• 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: ethyl 2-methyl-2-{[4-({[(4-methyl-2-{4-[(methylsulfonyl)oxy]phenyl}-1,3-thiazol-5-yl)carbonyl]amino}methyl)phenyl]oxy}propanoate
• 英文别名: Ethyl 2-methyl-2-[4-[[[4-methyl-2-(4-methylsulfonyloxyphenyl)-1,3-thiazole-5-carbonyl]amino]methyl]phenoxy]propanoate
• CAS: 929693-91-4
• 化学式: C₂₅H₂₈N₂O₇S₂
• 分子量: 532.639
• InChiKey: VYPXHEMNCQHEPT-UHFFFAOYSA-N

物化性质

• 密度：
  1.299±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  36
• 可旋转键数：
  11
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  158
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  ethyl 2-methyl-2-{[4-({[(4-methyl-2-{4-[(methylsulfonyl)oxy]phenyl}-1,3-thiazol-5-yl)carbonyl]amino}methyl)phenyl]oxy}propanoate 在 sodium hydroxide 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 反应 4.0h， 以74%的产率得到2-[4-({[2-(4-Hydroxyphenyl)-4-methyl-1,3-thiazol-5-yl]formamido}methyl)phenoxy]-2-methylpropanoic acid
  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
• 作为产物：
  描述：

  4-羟基硫代苯甲酰胺 在 sodium hydroxide 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 乙醇 、 水 、 N,N-二甲基甲酰胺 、 丙酮 、 甲苯 为溶剂， 反应 49.5h， 生成 ethyl 2-methyl-2-{[4-({[(4-methyl-2-{4-[(methylsulfonyl)oxy]phenyl}-1,3-thiazol-5-yl)carbonyl]amino}methyl)phenyl]oxy}propanoate
  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