methyl 3-hydroxy-5-((1-methoxypropan-2-yl)oxy)benzoate | 1259614-15-7

• 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-hydroxy-5-((1-methoxypropan-2-yl)oxy)benzoate
• 英文别名: methyl 3-hydroxy-5-(1-methoxypropan-2-yloxy)benzoate
• CAS: 1259614-15-7
• 化学式: C₁₂H₁₆O₅
• 分子量: 240.256
• InChiKey: JGIXKHBUAQEBSU-UHFFFAOYSA-N

物化性质

• 沸点：
  371.5±32.0 °C(Predicted)
• 密度：
  1.166±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  17
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  65
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  methyl 3-hydroxy-5-((1-methoxypropan-2-yl)oxy)benzoate 在 copper(l) iodide 、 2,2,6,6-四甲基-3,5-庚二酮 、 caesium carbonate 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 3.5h， 生成 3-((1-methoxypropan-2-yl)oxy)-5-(4-(methylsulfonyl)phenoxy)-N-(5-(pyridin-2-yl)-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)benzamide
  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-(benzyloxy)-5-(1-methoxypropan-2-yloxy)benzoate 在 钯 氢气 、 甲醇 、 四氢呋喃 作用下， 以 甲醇 为溶剂， 反应 16.0h， 以to give methyl 3-hydroxy-5-(1-methoxypropan-2-yloxy)benzoate (8 g, 33.33 mmol, 98%) as white solid的产率得到methyl 3-hydroxy-5-((1-methoxypropan-2-yl)oxy)benzoate
  参考文献：
  名称：

  Disubstituted benzamide derivatives as glucokinase (GK) activators

  摘要：

  本发明涉及一般式（I）的二取代苯甲酰胺衍生物，其药学上可接受的盐，药学上可接受的溶剂化物，对映体，非对映体异构体，前药，代谢物和多晶形。本发明还涉及制备本发明化合物的方法，含有该化合物的制药组合物以及使用本发明化合物治疗II型糖尿病的方法。

  公开号：

  US08450494B2

文献信息

• [EN] DISUBSTITUTED BENZAMIDE DERIVATIVES AS GLUCOKINASE (GK) ACTIVATORS<br/>[FR] DÉRIVÉS DE BENZAMIDES DISUBSTITUÉS ET UTILISÉS COMME ACTIVATEURS DE LA GLUCOKINASE (GK)
  申请人：CADILA HEALTHCARE LTD

  公开号：WO2010150280A1

  公开（公告）日：2010-12-29

  The invention relates to disubstituted benzamide derivatives of the general Formula (I), their pharmaceutically acceptable salts, pharmaceutically acceptable solvates, enantiomers, diastereomers, prodrugs, metabolites and polymorphs. The invention also relates to processes for the preparation of the compounds of the invention, pharmaceutical compositions containing the compounds and to methods for treating type II diabetes using the compounds of the invention.

  该发明涉及一般式（I）的二取代苯甲酰胺衍生物，其药学上可接受的盐、药学上可接受的溶剂化合物、对映体、非对映体、前药、代谢物和多型体。该发明还涉及制备该发明化合物的方法、含有该化合物的药物组合物以及使用该发明化合物治疗2型糖尿病的方法。
• 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。
• 2-PHENYL SUBSTITUTED IMIDAZOL [4,5B] PYRIDINE/PYRAZINE AND PURINE DERIVATIVES AS GLUCOKINASE MODULATORS
  申请人：Caulkett Peter William Rodney

  公开号：US20110059941A1

  公开（公告）日：2011-03-10

  Compounds of Formula (I), wherein R 1 -R 10 , A and X 1 to X 3 are as described in the specification, and their salts and pro-drugs, are activators of glucokinase (GLK) and are thereby useful in the treatment of, for example, type 2 diabetes. Processes for preparing compounds of formula (I) are also described.

  公式（I）的化合物，其中R1-R10，A和X1到X3如规范所述，并且它们的盐和前药是葡萄糖激酶（GLK）的激活剂，因此在治疗例如2型糖尿病方面是有用的。还描述了制备公式（I）化合物的过程。
• DISUBSTITUTED BENZAMIDE DERIVATIVES AS GLUCOKINASE (GK) ACTIVATORS
  申请人：Kharul Rajendra

  公开号：US20120149704A1

  公开（公告）日：2012-06-14

  The invention relates to disubstituted benzamide derivatives of the general Formula (I), their pharmaceutically acceptable salts, pharmaceutically acceptable solvates, enantiomers, diastereomers, prodrugs, metabolites and polymorphs. The invention also relates to processes for the preparation of the compounds of the invention, pharmaceutical compositions containing the compounds and to methods for treating type II diabetes using the compounds of the invention.

  本发明涉及一般式（I）的二取代苯甲酰胺衍生物、其药学上可接受的盐、药学上可接受的溶剂化物、对映体、非对映异构体、前药、代谢物和多晶形。本发明还涉及制备本发明化合物的方法、含有该化合物的制药组合物以及使用该化合物治疗II型糖尿病的方法。
• Benzamide derivatives and their use as glucokinase activating agents.
  申请人：AstraZeneca AB

  公开号：EP2048137A1

  公开（公告）日：2009-04-15

  Methyl 3-hydroxy-5-[(1S)-2-methoxy-(1-methylethyl)oxy]benzoate, which is useful as a chemical intermediate, is claimed.

  权利要求 3-羟基-5-[(1S)-2-甲氧基-(1-甲基乙基)氧基]苯甲酸甲酯可用作化学中间体。