3-Isopropoxy-5-(2-(3-thienyl)ethoxy)benzoic acid | 852520-52-6

• 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: 3-Isopropoxy-5-(2-(3-thienyl)ethoxy)benzoic acid
• 英文别名: 3-isopropoxy-5-(2-thiophen-3-yl-ethoxy)-benzoic acid；3-isopropoxy-5-(2-thiophene-3-yl-ethoxy)-benzoic acid；3-propan-2-yloxy-5-(2-thiophen-3-ylethoxy)benzoic acid
• CAS: 852520-52-6
• 化学式: C₁₆H₁₈O₄S
• 分子量: 306.383
• InChiKey: BXOPNHUQVVADJE-UHFFFAOYSA-N

物化性质

• 沸点：
  492.5±40.0 °C(Predicted)
• 密度：
  1.225±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  21
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  84
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3-Isopropoxy-5-(2-(3-thienyl)ethoxy)benzoic acid 在 吡啶 、 草酰氯 、 N,N-二甲基甲酰胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 2.0h， 生成 methyl 6-(3-isopropoxy-5-(2-(3-thienyl)ethoxy)benzamido)nicotinate
  参考文献：
  名称：

  Small-Molecule Allosteric Activation of Human Glucokinase in the Absence of Glucose

  摘要：

  Synthetic allosteric activators of human glucokinase are receiving considerable attention as potential diabetes therapeutic agents. Although their mechanism of action is not fully understood, structural studies suggest that activator association requires prior formation of a binary enzyme glucose complex. Here, we demonstrate that three previously described activators associate with glucokinase in a glucose-independent fashion. Transient-state kinetic assays reveal a lag in enzyme progress curves that is systematically reduced when the enzyme is preincubated with activators. Isothermal titration calorimetry demonstrates that activator binding is enthalpically driven for all three compounds, whereas the entropic changes accompanying activator binding can be favorable or unfavorable. Viscosity variation experiments indicate that the k(cat) value of glucokinase is almost fully limited by product release, both in the presence and absence of activators, suggesting that activators impact a step preceding product release. The observation of glucose-independent allosteric activation of glucokinase has important implications for the refinement of future diabetes therapeutics and for the mechanism of kinetic cooperativity of mammalian glucokinase.

  DOI：

  10.1021/ml400061x
• 作为产物：
  描述：

  3-(2-溴乙基)噻吩 在 potassium carbonate 、 sodium hydroxide 作用下， 以 四氢呋喃 、 乙腈 为溶剂， 反应 0.75h， 生成 3-Isopropoxy-5-(2-(3-thienyl)ethoxy)benzoic acid
  参考文献：
  名称：

  Small-Molecule Allosteric Activation of Human Glucokinase in the Absence of Glucose

  摘要：

  Synthetic allosteric activators of human glucokinase are receiving considerable attention as potential diabetes therapeutic agents. Although their mechanism of action is not fully understood, structural studies suggest that activator association requires prior formation of a binary enzyme glucose complex. Here, we demonstrate that three previously described activators associate with glucokinase in a glucose-independent fashion. Transient-state kinetic assays reveal a lag in enzyme progress curves that is systematically reduced when the enzyme is preincubated with activators. Isothermal titration calorimetry demonstrates that activator binding is enthalpically driven for all three compounds, whereas the entropic changes accompanying activator binding can be favorable or unfavorable. Viscosity variation experiments indicate that the k(cat) value of glucokinase is almost fully limited by product release, both in the presence and absence of activators, suggesting that activators impact a step preceding product release. The observation of glucose-independent allosteric activation of glucokinase has important implications for the refinement of future diabetes therapeutics and for the mechanism of kinetic cooperativity of mammalian glucokinase.

  DOI：

  10.1021/ml400061x

文献信息

• IMIDAZOPYRIDINE COMPOUNDS
  申请人：Iwata Hidehisa

  公开号：US20100069431A1

  公开（公告）日：2010-03-18

  Compounds, pharmaceutical compositions, kits and methods are provided for use with glucokinase that comprise a compound selected from the group consisting of formula (I) wherein the variables are as defined herein.

  提供了用于与葡萄糖激酶一起使用的化合物、药物组合物、试剂盒和方法，其中包括从以下公式(I)所述的组中选择的化合物，其中变量如本文所定义。
• [EN] N- ( PYRAZOLE- 3 -YL) -BENZAMIDE DERIVATIVES AS GLUCOKINASE ACTIVATORS<br/>[FR] DÉRIVÉS DE N-(PYRAZOL-3-YL)-BENZAMIDE COMME ACTIVATEURS DE GLUCOKINASE
  申请人：MERCK PATENT GMBH

  公开号：WO2009046802A1

  公开（公告）日：2009-04-16

  Novel heterocyclic compounds of the formula (I) in which R1, R2, R3, R4, R5, R6, R7, Alk and D have the meanings indicate in Claim 1, are activators of glucokinase and can be used for the prevention and/or treatment of Diabetes Typ 1 and 2, obesity, neuropathy and/or nephropathy.

  化学式（I）中的新型杂环化合物，其中R1、R2、R3、R4、R5、R6、R7、Alk和D的含义如权利要求书中所示，是葡萄糖激酶的激活剂，可用于预防和/或治疗糖尿病1型和2型、肥胖症、神经病和/或肾病。
• N-(PYRAZOLE-3-YL)-BENZAMIDE DERIVATIVES AS GLUCOKINASE ACTIVATORS
  申请人：Burgdorf Lars Thore

  公开号：US20100210690A1

  公开（公告）日：2010-08-19

  Novel heterocyclic compounds of the formula I in which R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , Alk and D have the meanings indicated in claim 1, are activators of glucokinase and can be used for the prevention and/or treatment of Diabetes Typ 1 and 2, obesity, neuropathy and/or nephropathy.

  式I中的新型杂环化合物，其中R1，R2，R3，R4，R5，R6，R7，Alk和D具有权利要求1中所示的含义，是葡萄糖激酶的激活剂，可用于预防和/或治疗1型和2型糖尿病、肥胖症、神经病和/或肾病。
• NOVEL ACTIVATORS OF GLUCOKINASE
  申请人：Tian Feng

  公开号：US20110294758A1

  公开（公告）日：2011-12-01

  The present invention provides for novel compounds of Formulas I and II and pharmaceutically acceptable salts and co-crystals thereof which have glucokinsae activator activity. The present invention further provides for pharmaceutical compositions comprising the same as well as methods of treating, preventing, delaying the time to onset or reducing the risk for the development or progression of a disease or condition for which one or more glucokinase activator is indicated, including Type 1 and 2 diabetes, impaired glucose tolerance, insulin resistance and hyperglycemia. The present invention also provides for processes of making the compounds of Formulas I and II, including salts and co-crystals thereof, and pharmaceutical compositions comprising the same.

  本发明提供了I和II式的新型化合物，以及其药学上可接受的盐和共晶体，具有葡萄糖激酶激活剂活性。本发明还提供了包括该化合物的制药组合物，以及治疗、预防、延迟发病时间或减少一种或多种葡萄糖激酶激活剂所指示的疾病或症状发展或进展的方法，包括1型和2型糖尿病、糖耐量受损、胰岛素抵抗和高血糖。本发明还提供了制备I和II式化合物（包括其盐和共晶体）以及包括该化合物的制药组合物的方法。
• N-(pyrazole-3-yl)-benzamide derivatives as glucokinase activators
  申请人：Merck Patent Gesellschaft mit Beschränkter Haftung

  公开号：US08236824B2

  公开（公告）日：2012-08-07

  Novel heterocyclic compounds of the formula I in which R1, R2, R3, R4, R5, R6, R7, Alk and D have the meanings indicated in claim 1, are activators of glucokinase and can be used for the prevention and/or treatment of Diabetes Typ 1 and 2, obesity, neuropathy and/or nephropathy.

  式I中的新型杂环化合物，其中R1、R2、R3、R4、R5、R6、R7、Alk和D具有权利要求书1中所示的含义，是葡萄糖激酶的激活剂，可用于预防和/或治疗1型和2型糖尿病、肥胖症、神经病和/或肾病。