3-[4-(2-{6-[2-(3,5-dimethoxyphenyl)vinyl]-2-oxobenzothiazol-3-yl}ethoxy)phenyl]-2-(2,2,2-trifluoroethoxy)propionic acid

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 二苯乙烯类
• 英文名称: 3-[4-(2-{6-[2-(3,5-dimethoxyphenyl)vinyl]-2-oxobenzothiazol-3-yl}ethoxy)phenyl]-2-(2,2,2-trifluoroethoxy)propionic acid
• 化学式: C₃₀H₂₈F₃NO₇S
• 分子量: 603.616
• InChiKey: FHWDYHYHAMRIIE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.9
• 重原子数：
  42.0
• 可旋转键数：
  13.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  96.22
• 氢给体数：
  1.0
• 氢受体数：
  8.0

反应信息

• 作为反应物：
  描述：

  3-[4-(2-{6-[2-(3,5-dimethoxyphenyl)vinyl]-2-oxobenzothiazol-3-yl}ethoxy)phenyl]-2-(2,2,2-trifluoroethoxy)propionic acid 、 盐酸甲胺 在 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 二氯甲烷 为溶剂， 反应 2.0h， 以90%的产率得到3-[4-(2-{6-[2-(3,5-dimethoxyphenyl)vinyl]-2-oxobenzothiazol-3-yl}ethoxy)phenyl]-2-ethoxy-N-methylpropionamide
  参考文献：
  名称：

  Anti-diabetic activity of fused PPARγ-SIRT1 ligands with limited body-weight gain by mimicking calorie restriction and decreasing SGK1 expression

  摘要：

  A series of benzothiazol-2-one containing alpha-ethoxyphenylpropionic acid derivatives incorporating resveratrol or butein scaffolds were designed as fused full PPAR gamma agonist ligands and SIRT1-activating compounds for the treatment of type 2 diabetes (T2D) and its complications. Compound 14d displayed the best in vitro pharmacological profile with full PPAR gamma agonist activity (Emax = 98%, EC50 = 200 nM), SIRTI enzymatic activation (+128%) and SGK1 expression inhibition (- 57%) which is known to limit side effects as fluid retention and body-weight gain. Compound 14d showed high efficacy in an ob/ob mice model with significant decreases in serum triglyceride, glucose and insulin levels but mostly with limited body-weight gain by mimicking calorie restriction (CR) and inhibiting SGKI expression. (C) 2017 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2017.06.006
• 作为产物：
  描述：

  2-羟基苯并噻唑 在 水 、 溴 、 palladium diacetate 、 potassium carbonate 、 三苯基膦 、 lithium hydroxide 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 19.0h， 生成 3-[4-(2-{6-[2-(3,5-dimethoxyphenyl)vinyl]-2-oxobenzothiazol-3-yl}ethoxy)phenyl]-2-(2,2,2-trifluoroethoxy)propionic acid
  参考文献：
  名称：

  Anti-diabetic activity of fused PPARγ-SIRT1 ligands with limited body-weight gain by mimicking calorie restriction and decreasing SGK1 expression

  摘要：

  A series of benzothiazol-2-one containing alpha-ethoxyphenylpropionic acid derivatives incorporating resveratrol or butein scaffolds were designed as fused full PPAR gamma agonist ligands and SIRT1-activating compounds for the treatment of type 2 diabetes (T2D) and its complications. Compound 14d displayed the best in vitro pharmacological profile with full PPAR gamma agonist activity (Emax = 98%, EC50 = 200 nM), SIRTI enzymatic activation (+128%) and SGK1 expression inhibition (- 57%) which is known to limit side effects as fluid retention and body-weight gain. Compound 14d showed high efficacy in an ob/ob mice model with significant decreases in serum triglyceride, glucose and insulin levels but mostly with limited body-weight gain by mimicking calorie restriction (CR) and inhibiting SGKI expression. (C) 2017 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2017.06.006

文献信息

• Anti-diabetic activity of fused PPARγ-SIRT1 ligands with limited body-weight gain by mimicking calorie restriction and decreasing SGK1 expression
  作者：Celine Pirat、Catherine Dacquet、Veronique Leclerc、Nathalie Hennuyer、Monique Beucher-Gaudin、Ghislaine Zanirato、Anne Géant、Bart Staels、Alain Ktorza、Amaury Farce、Daniel-Henri Caignard、Pascal Berthelot、Nicolas Lebegue

  DOI：10.1016/j.ejmech.2017.06.006

  日期：2017.9

  A series of benzothiazol-2-one containing alpha-ethoxyphenylpropionic acid derivatives incorporating resveratrol or butein scaffolds were designed as fused full PPAR gamma agonist ligands and SIRT1-activating compounds for the treatment of type 2 diabetes (T2D) and its complications. Compound 14d displayed the best in vitro pharmacological profile with full PPAR gamma agonist activity (Emax = 98%, EC50 = 200 nM), SIRTI enzymatic activation (+128%) and SGK1 expression inhibition (- 57%) which is known to limit side effects as fluid retention and body-weight gain. Compound 14d showed high efficacy in an ob/ob mice model with significant decreases in serum triglyceride, glucose and insulin levels but mostly with limited body-weight gain by mimicking calorie restriction (CR) and inhibiting SGKI expression. (C) 2017 Elsevier Masson SAS. All rights reserved.