5-[[4-[(4-Bromophenyl)methoxy]phenyl]methylidene]-1,3-thiazolidine-2,4-dione

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 5-[[4-[(4-Bromophenyl)methoxy]phenyl]methylidene]-1,3-thiazolidine-2,4-dione
• 化学式: C₁₇H₁₂BrNO₃S
• 分子量: 390.257
• InChiKey: LKOZFNYADKCUDT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  80.7
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  5-[[4-[(4-Bromophenyl)methoxy]phenyl]methylidene]-1,3-thiazolidine-2,4-dione 在 cobalt(II) chloride hexahydrate 、 二甲基乙二醛肟 、 sodium hydroxide 、 sodium tetrahydroborate 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 、 水 为溶剂， 反应 16.5h， 以80%的产率得到5-(4-((4-bromobenzyl)oxy)benzyl)thiazolidine-2,4-dione
  参考文献：
  名称：

  Design, synthesis, and biological evaluation of novel thiazolidinediones as PPARγ/FFAR1 dual agonists

  摘要：

  Diabetes mellitus is a chronic metabolic disorder that affects more than 180 million people worldwide. Peroxisome proliferator activated receptors (PPARs) are a group of nuclear receptors that have been targeted by the thiazolidinedione (TZD) class of compounds for the management of type II diabetes. PPAR gamma is known to regulate adipogenesis and glucose metabolism. Another emerging target for the design of antidiabetic agents is the free fatty acid receptor 1 (FFAR1), previously known as GPR40. Agonists of this receptor were found to enhance insulin secretion in diabetic patients. It has been reported that some thiazolidinediones (TZDs) activate FFAR1 with micromolar potency. In this study, based on docking studies into the crystal structure of PPAR gamma and a homology model of FFAR1, nineteen compounds were designed, synthesized, and biologically tested for agonistic activity on both receptors. Nine compounds showed promising dual activity, with two compounds, 11a and 5b, having affinities in the low micromolar range on both targets. These molecules represent the first antidiabetic agents that could act as insulin sensitizers as well as insulin secretagogues. (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.12.049
• 作为产物：
  描述：

  4-溴苄醇 在 哌啶 、 偶氮二甲酸二异丙酯 、 三苯基膦 、 苯甲酸 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 反应 32.0h， 生成 5-[[4-[(4-Bromophenyl)methoxy]phenyl]methylidene]-1,3-thiazolidine-2,4-dione
  参考文献：
  名称：

  Design, synthesis, and biological evaluation of novel thiazolidinediones as PPARγ/FFAR1 dual agonists

  摘要：

  Diabetes mellitus is a chronic metabolic disorder that affects more than 180 million people worldwide. Peroxisome proliferator activated receptors (PPARs) are a group of nuclear receptors that have been targeted by the thiazolidinedione (TZD) class of compounds for the management of type II diabetes. PPAR gamma is known to regulate adipogenesis and glucose metabolism. Another emerging target for the design of antidiabetic agents is the free fatty acid receptor 1 (FFAR1), previously known as GPR40. Agonists of this receptor were found to enhance insulin secretion in diabetic patients. It has been reported that some thiazolidinediones (TZDs) activate FFAR1 with micromolar potency. In this study, based on docking studies into the crystal structure of PPAR gamma and a homology model of FFAR1, nineteen compounds were designed, synthesized, and biologically tested for agonistic activity on both receptors. Nine compounds showed promising dual activity, with two compounds, 11a and 5b, having affinities in the low micromolar range on both targets. These molecules represent the first antidiabetic agents that could act as insulin sensitizers as well as insulin secretagogues. (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.12.049