methyl 3-(cyclopentyloxy)-5-(4-(methylsulfonyl)phenoxy)benzoate | 939054-38-3

• 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: methyl 3-(cyclopentyloxy)-5-(4-(methylsulfonyl)phenoxy)benzoate
• 英文别名: methyl 3-cyclopentyloxy-5-(4-methylsulfonylphenoxy)benzoate
• CAS: 939054-38-3
• 化学式: C₂₀H₂₂O₆S
• 分子量: 390.457
• InChiKey: WPPGEFAYTHAXHX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  27
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  87.3
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  methyl 3-(cyclopentyloxy)-5-(4-(methylsulfonyl)phenoxy)benzoate 在 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 以67%的产率得到3-(cyclopentyloxy)-5-(4-(methylsulfonyl)phenoxy)benzoic acid
  参考文献：
  名称：

  Discovery of cycloalkyl-fused N-thiazol-2-yl-benzamides as tissue non-specific glucokinase activators: Design, synthesis, and biological evaluation

  摘要：

  Glucokinase (GK) activators are being developed for the treatment of type 2 diabetes mellitus (T2DM). However, existing GK activators have risks of hypoglycemia caused by over-activation of GK in islet cells and dyslipidemia caused by over-activation of intrahepatic GK. In the effort to mitigate risks of hypoglycemia and dyslipidemia while maintaining the promising efficacy of GK activator, we investigated a series of cycloalkyl-fused N-thiazol-2-yl-benzamides as tissue non-specific partial GK activators, which led to the identification of compound 72 that showed a good balance between in vitro potency and enzyme kinetic parameters, and protected beta-cells from streptozotocin-induced apoptosis. Chronic treatment of compound 72 demonstrated its potent activity in regulation of glucose homeostasis and low risk of dyslipidemia with diabetic db/db mice in oral glucose tolerance test (OGTT). Moreover, acute treatment of compound 72 did not induce hypoglycemia in C57BL/6J mice even at 200 mg/kg via oral administration. (C) 2017 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2017.07.051
• 作为产物：
  描述：

  methyl 3-(cyclopentyloxy)-5-(4-(methylthio)phenoxy)benzoate 在 间氯过氧苯甲酸 作用下， 以 氯仿 为溶剂， 生成 methyl 3-(cyclopentyloxy)-5-(4-(methylsulfonyl)phenoxy)benzoate
  参考文献：
  名称：

  Structure–activity relationships of 3,5-disubstituted benzamides as glucokinase activators with potent in vivo efficacy

  摘要：

  The optimization of our lead GK activator 2a to 3-[(1S)-2-hydroxy-1-methylethoxy]-5-[4-(methylsulfonyl) phenoxy]-N-1,3-thiazol-2-ylbenzamide (6g), a potent GK activator with good oral availability, is described, including to uncouple the relationship between potency and hydrophobicity. Following oral administration, this compound exhibited robust glucose lowering in diabetic model rodents. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2009.04.040
• 作为试剂：
  描述：

  Methyl 5-(benzyloxy)-2-(1-methoxypropan-2-yloxy)benzoate 、 3-羟基-5-(4-(甲基磺酰基)苯氧基)苯甲酸甲酯 、 环戊醇 在 methyl 3-(cyclopentyloxy)-5-(4-(methylsulfonyl)phenoxy)benzoate 作用下， 生成 methyl 3-(cyclopentyloxy)-5-(4-(methylsulfonyl)phenoxy)benzoate
  参考文献：
  名称：

  GLUCOKINASE ACTIVATORS

  摘要：

  提供了与葡萄糖激酶一起使用的化合物、药物组合物、工具箱和方法，其中包括从以下组中选择的化合物：其中变量的定义如本文所述。

  公开号：

  US20110070297A1

文献信息

• [EN] GLUCOKINASE ACTIVATORS<br/>[FR] ACTIVATEURS DE LA GLUCOKINASE
  申请人：TAKEDA SAN DIEGO INC

  公开号：WO2007061923A2

  公开（公告）日：2007-05-31

  [EN] 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.
  [FR] L'invention porte sur des composés des préparations pharmaceutiques des trousses et des méthodes s'utilisant avec la glucokinase et comportant un composé sélectionné dans le groupe de formule (I) dont les variables sont définies dans la description.
• Structure–activity relationships of 3,5-disubstituted benzamides as glucokinase activators with potent in vivo efficacy
  作者：Tomoharu Iino、Noriaki Hashimoto、Kaori Sasaki、Sumika Ohyama、Riki Yoshimoto、Hideka Hosaka、Takuro Hasegawa、Masato Chiba、Yasufumi Nagata、Jun-ichi Eiki、Teruyuki Nishimura

  DOI：10.1016/j.bmc.2009.04.040

  日期：2009.6

  The optimization of our lead GK activator 2a to 3-[(1S)-2-hydroxy-1-methylethoxy]-5-[4-(methylsulfonyl) phenoxy]-N-1,3-thiazol-2-ylbenzamide (6g), a potent GK activator with good oral availability, is described, including to uncouple the relationship between potency and hydrophobicity. Following oral administration, this compound exhibited robust glucose lowering in diabetic model rodents. (C) 2009 Elsevier Ltd. All rights reserved.
• Discovery of cycloalkyl-fused N-thiazol-2-yl-benzamides as tissue non-specific glucokinase activators: Design, synthesis, and biological evaluation
  作者：Zhengyu Wang、Xiaofan Shi、Huan Zhang、Liang Yu、Yanhua Cheng、Hefeng Zhang、Huibin Zhang、Jinpei Zhou、Jing Chen、Xu Shen、Wenhu Duan

  DOI：10.1016/j.ejmech.2017.07.051

  日期：2017.10

  Glucokinase (GK) activators are being developed for the treatment of type 2 diabetes mellitus (T2DM). However, existing GK activators have risks of hypoglycemia caused by over-activation of GK in islet cells and dyslipidemia caused by over-activation of intrahepatic GK. In the effort to mitigate risks of hypoglycemia and dyslipidemia while maintaining the promising efficacy of GK activator, we investigated a series of cycloalkyl-fused N-thiazol-2-yl-benzamides as tissue non-specific partial GK activators, which led to the identification of compound 72 that showed a good balance between in vitro potency and enzyme kinetic parameters, and protected beta-cells from streptozotocin-induced apoptosis. Chronic treatment of compound 72 demonstrated its potent activity in regulation of glucose homeostasis and low risk of dyslipidemia with diabetic db/db mice in oral glucose tolerance test (OGTT). Moreover, acute treatment of compound 72 did not induce hypoglycemia in C57BL/6J mice even at 200 mg/kg via oral administration. (C) 2017 Elsevier Masson SAS. All rights reserved.
• GLUCOKINASE ACTIVATORS
  申请人：Cao X. Sheldon

  公开号：US20070197532A1

  公开（公告）日：2007-08-23

  Compounds, pharmaceutical compositions, kits and methods are provided for use with glucokinase that comprise a compound selected from the group consisting of: 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，其中包括从以下组中选择的化合物：其中变量如本文所定义。