methyl 3-(2-aminothiazol-5-yl)oxybenzoate | 1001327-26-9

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: methyl 3-(2-aminothiazol-5-yl)oxybenzoate
• 英文别名: methyl 3-[(2-amino-1,3-thiazol-5-yl)oxy]benzoate
• CAS: 1001327-26-9
• 化学式: C₁₁H₁₀N₂O₃S
• 分子量: 250.278
• InChiKey: ORDFITICZXDPME-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  103
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  methyl 3-(2-aminothiazol-5-yl)oxybenzoate 在 lithium hydroxide 、 N-羟基-7-氮杂苯并三氮唑 、 草酰氯 、 水 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 、 N,N-二甲基甲酰胺 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 61.0h， 生成 N-[5-[3-(azetidine-1-carbonyl)phenoxy]-1,3-thiazol-2-yl]-3-[(2S)-1-methoxypropan-2-yl]oxy-5-(4-methylsulfonylphenoxy)benzamide
  参考文献：
  名称：

  WO2008/154563

  摘要：

  公开号：
• 作为产物：
  描述：

  3-羟基苯甲酸甲酯 、 2-氨基-5-溴-噻唑氢溴酸盐 在 caesium carbonate 作用下， 以 丙酮 为溶剂， 反应 15.0h， 以34%的产率得到methyl 3-(2-aminothiazol-5-yl)oxybenzoate
  参考文献：
  名称：

  NOVEL GLUCOKINASE ACTIVATORS AND METHODS OF USING SAME

  摘要：

  提供了一种葡萄糖激酶激活剂，因此对治疗糖尿病和相关疾病有用，并具有以下结构：环中表示一个或两个双键；R1是芳基或杂环芳基；R2是卤素、环烷基、杂环烷基、芳基或杂环芳基；R5如本文所定义；Z为O、S、S(O)、S(O)2或NR5a；X为S、O、N、NR3或CR3；Y为NCR4或N4；R3、R4和R5如本文所定义；R8是芳基或杂环芳基；R6和R7独立地为H、卤素或烷基；m为0或1；n为0至3，或其药用盐。还提供了一种利用上述化合物治疗糖尿病和相关疾病的方法。

  公开号：

  US20080021052A1

文献信息

• ACETAMIDE DERIVATIVES AS GLUCOKINASE ACTIVATORS, THEIR PROCESS AND MEDICINAL APPLICATION
  申请人：Bhuniya Debnath

  公开号：US20100310493A1

  公开（公告）日：2010-12-09

  Acetamide derivatives, their stereoisomers, tautomers, prodrugs, pharmaceutically acceptable salts, polymorphs, solvates and formulations thereof for the prophylaxis, management, treatment, control of progression, or adjunct treatment of diseases and/or medical conditions where the activation of glucokinase would be beneficial, are disclosed. The disclosure also provides process of preparation of these acetamide derivatives.

  乙酰胺衍生物，它们的立体异构体、互变异构体、前药、药用可接受盐、多型体、溶剂合物及其配方，用于预防、管理、治疗、控制疾病和/或医疗状况的进展，或者作为激活葡萄糖激酶有益时的辅助治疗，已被披露。该披露还提供了这些乙酰胺衍生物的制备方法。
• ACETAMIDE DERIVATIVES AS GLUCOKINASE ACTIVATORS, THEIR PROCESS AND MEDICINAL APPLICATIONS
  申请人：Bhuniya Debnath

  公开号：US20120214735A1

  公开（公告）日：2012-08-23

  Acetamide derivatives, their stereoisomers, tautomers, prodrugs, pharmaceutically acceptable salts, polymorphs, solvates and formulations thereof for the prophylaxis, management, treatment, control of progression, or adjunct treatment of diseases and/or medical conditions where the activation of glucokinase would be beneficial, are disclosed. The disclosure also provides process of preparation of these acetamide derivatives.

  本文披露了乙酰胺衍生物及其立体异构体、互变异构体、前药、药学上可接受的盐、多晶形、溶剂化物和制剂，用于预防、管理、治疗、控制进展或辅助治疗激活葡萄糖激酶有益的疾病和/或医疗条件。此外，本文还提供了制备这些乙酰胺衍生物的过程。
• NOVEL SPIROINDOLINE COMPOUND, AND MEDICINAL AGENT COMPRISING SAME
  申请人：KOWA COMPANY, LTD.

  公开号：US20140309207A1

  公开（公告）日：2014-10-16

  The present invention provides a novel compound represented by a general formula (1) as shown below, which has a glucokinase-activating action in the liver and pancreatic β-cells and which is useful as an agent for preventing and/or treating diseases caused by hyperglycemia, such as diabetes. A spiroindoline compound represented by the general formula (1), or a salt thereof, or a solvate of the compound or the salt: [wherein ring A represents a nitrogen-containing 5-10 membered heteroaryl group; R 1 and R 2 , which are the same or different, each represent a hydrogen atom, a halogen atom, a halo C 1-6 alkyl group, a C 6-10 aryl group, a cyano group, a C 1-6 alkyl group optionally having a substituent, a C 2-6 alkenyl group optionally having a substituent, etc.; R 3 represents a hydrogen atom, a C 1-6 alkyl group optionally having a substituent, etc.; and R 4 represents a hydrogen atom, a halogen atom, a C 1-6 alkyl group optionally having a substituent, etc.]

  本发明提供了一种新型化合物，其通式（1）如下所示，具有在肝脏和胰岛β细胞中激活葡萄糖激酶的作用，并可用作预防和/或治疗由高血糖引起的疾病，如糖尿病的药物。该通式（1）表示的螺环吲哚化合物，或其盐，或化合物或盐的溶剂：[其中环A代表含氮的5-10成员杂环基；R1和R2，相同或不同，分别代表氢原子，卤原子，卤代C1-6烷基，C6-10芳基，氰基，C1-6烷基，可选取代基，C2-6烯基，可选取代基等；R3代表氢原子，C1-6烷基，可选取代基等；R4代表氢原子，卤原子，C1-6烷基，可选取代基等。]
• Acetamide derivatives as glucokinase activators, their process and medicinal applications
  申请人：Bhuniya Debnath

  公开号：US09340506B2

  公开（公告）日：2016-05-17

  Acetamide derivatives, their stereoisomers, tautomers, prodrugs, pharmaceutically acceptable salts, polymorphs, solvates and formulations thereof for the prophylaxis, management, treatment, control of progression, or adjunct treatment of diseases and/or medical conditions where the activation of glucokinase would be beneficial, are disclosed. The disclosure also provides process of preparation of these acetamide derivatives.

  本文披露了乙酰胺衍生物及其立体异构体、互变异构体、前药、药学上可接受的盐、多晶体、溶剂化物和制剂，用于预防、管理、治疗、控制进展或辅助治疗激活葡萄糖激酶有益的疾病和/或医疗条件。本文还提供了这些乙酰胺衍生物的制备方法。
• Discovery of liver-directed glucokinase activator having anti-hyperglycemic effect without hypoglycemia
  作者：Anil M. Deshpande、Debnath Bhuniya、Siddhartha De、Bhavesh Dave、Vinod P. Vyavahare、Santosh H. Kurhade、Sachin R. Kandalkar、Keshav P. Naik、Balasaheb S. Kobal、Rahul D. Kaduskar、Sujay Basu、Vaibhav Jain、Pratima Patil、Sandhya Chaturvedi Joshi、Ganesh Bhat、Amol A. Raje、Satyanarayana Reddy、Jayasagar Gundu、Vamsi Madgula、Suhas Tambe、Prasad Shitole、Dhananjay Umrani、Anita Chugh、Venkata P. Palle、Kasim A. Mookhtiar

  DOI：10.1016/j.ejmech.2017.03.042

  日期：2017.6

  Glucokinase activators (GKAs) are among the emerging drug candidates for the treatment of type 2 diabetes (T2D). Despite effective blood glucose lowering in clinical trials, many pan-GKAs "acting both in pancreas and liver" have been discontinued from clinical development mainly because of their potential to cause hypoglycemia. Pan-GKAs over sensitize pancreatic GK, resulting in insulin secretion even at sub-normoglycemic level which might be a possible explanation for hypoglycemia. An alternative approach to minimize the risk of hypoglycemia is to use liver-directed GKAs, which are reported to be advancing well in clinical development. Here, we report the discovery and structure-activity relationship (SAR) studies on a novel 2-phenoxy-acetamide series with the aim of identifying a liver-directed GKA. Incorporation of a carboxylic acid moiety as an active hepatocyte uptake recognizing element at appropriate position of 2-phenoxy-acetamide core led to the identification of 26, a potent GKA with predominant liver-directed pharmacokinetics in mice. Compound 26 on oral administration significantly reduced blood glucose levels during an oral glucose tolerance test (oGTT) performed in diet-induced obese (DIO) mice, while showing no sign of hypoglycemia in normal C57 mice over a 10-fold dose range, even when dosed at fasted condition. Together, these data demonstrate a liver-directed GKA has beneficial effect on glucose homeostasis with reduced risk of hypoglycemia. (C) 2017 Elsevier Masson SAS. All rights reserved.