3-(benzyloxy)-5-bromo-N-(4-ethylthiazol-2-yl)pyridin-2-amine

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 3-(benzyloxy)-5-bromo-N-(4-ethylthiazol-2-yl)pyridin-2-amine
• 英文别名: N-(3-(benzyloxy)-5-bromopyridin-2-yl)-4-ethylthiazol-2-amine；N-(5-bromo-3-phenylmethoxypyridin-2-yl)-4-ethyl-1,3-thiazol-2-amine
• 化学式: C₁₇H₁₆BrN₃OS
• 分子量: 390.304
• InChiKey: ANSZFRWADMQBIE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  23
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  75.3
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3-(benzyloxy)-5-bromo-N-(4-ethylthiazol-2-yl)pyridin-2-amine 在 N-氯代丁二酰亚胺 作用下， 以 乙腈 为溶剂， 反应 1.0h， 以56.6%的产率得到N-(3-(benzyloxy)-5-bromopyridin-2-yl)-5-chloro-4-ethylthiazol-2-amine
  参考文献：
  名称：

  WO2007/53345

  摘要：

  公开号：
• 作为产物：
  描述：

  2-氨基-3-苄氧基吡啶 在 溴 、 potassium carbonate 、 三乙胺 作用下， 以 四氢呋喃 、 乙醇 、 氯仿 为溶剂， 反应 5.0h， 生成 3-(benzyloxy)-5-bromo-N-(4-ethylthiazol-2-yl)pyridin-2-amine
  参考文献：
  名称：

  Identification of a New Class of Glucokinase Activators through Structure-Based Design

  摘要：

  Glucose flux through glucokinase (GK) controls insulin release from the pancreas in response to high glucose concentrations. Glucose flux through GK also contributes to reducing hepatic glucose output. Because many individuals with type 2 diabetes appear to have an inadequacy or defect in one or both of these processes, compounds that can activate GK may serve as effective treatments for type 2 diabetes. Herein we report the identification and initial optimization of a novel series of allosteric glucokinase activators (GKAs). We discovered an initial thiazolylamino pyridine-based hit that was optimized using a structure-based design strategy and identified 26 as an early lead. Compound 26 demonstrated a good balance of in vitro potency and enzyme kinetic parameters and demonstrated blood glucose reductions in oral glucose tolerance tests in both C57BL/6J mice and high-fat fed Zucker diabetic fatty rats.

  DOI：

  10.1021/jm401116k

文献信息

• GLUCOKINASE ACTIVATORS
  申请人：Aicher Thomas D.

  公开号：US20100056530A1

  公开（公告）日：2010-03-04

  Provided are compounds of Formula I wherein R 1 , R 2 , Y, Z and G are as defined herein, that are useful in the treatment and/or prevention of diseases mediated by deficient levels of glucokinase activity, such as diabetes mellitus. Also provided are methods of treating or preventing diseases and disorders characterized by underactivity of glucokinase or which can be treated by activating glucokinase.

  提供了式I化合物，其中R1、R2、Y、Z和G的定义如本文所述，这些化合物对于治疗和/或预防由胰岛素敏感性激酶活性不足引起的疾病（如糖尿病）是有用的。还提供了治疗或预防由胰岛素敏感性激酶活性不足或可以通过激活胰岛素敏感性激酶来治疗的疾病和疾病的方法。
• Glucokinase activators
  申请人：Aicher Thomas D.

  公开号：US08933077B2

  公开（公告）日：2015-01-13

  Provided are compounds of Formula I wherein R1, R2, Y, Z and G are as defined herein, that are useful in the treatment and/or prevention of diseases mediated by deficient levels of glucokinase activity, such as diabetes mellitus. Also provided are methods of treating or preventing diseases and disorders characterized by underactivity of glucokinase or which can be treated by activating glucokinase.

  提供了I式化合物，其中R1，R2，Y，Z和G的定义如本文所述，这些化合物在治疗和/或预防由葡萄糖激酶活性不足介导的疾病，如糖尿病方面具有用途。还提供了用于治疗或预防由葡萄糖激酶活性不足或可以通过激活葡萄糖激酶治疗的疾病和障碍的方法。
• US8933077B2
  申请人：——

  公开号：US8933077B2

  公开（公告）日：2015-01-13
• WO2007/53345
  申请人：——

  公开号：——

  公开（公告）日：——
• Identification of a New Class of Glucokinase Activators through Structure-Based Design
  作者：Ronald J. Hinklin、Steven A. Boyd、Mark J. Chicarelli、Kevin R. Condroski、Walter E. DeWolf、Patrice A. Lee、Waiman Lee、Ajay Singh、Laurie Thomas、Walter C. Voegtli、Lance Williams、Thomas D. Aicher

  DOI：10.1021/jm401116k

  日期：2013.10.10

  Glucose flux through glucokinase (GK) controls insulin release from the pancreas in response to high glucose concentrations. Glucose flux through GK also contributes to reducing hepatic glucose output. Because many individuals with type 2 diabetes appear to have an inadequacy or defect in one or both of these processes, compounds that can activate GK may serve as effective treatments for type 2 diabetes. Herein we report the identification and initial optimization of a novel series of allosteric glucokinase activators (GKAs). We discovered an initial thiazolylamino pyridine-based hit that was optimized using a structure-based design strategy and identified 26 as an early lead. Compound 26 demonstrated a good balance of in vitro potency and enzyme kinetic parameters and demonstrated blood glucose reductions in oral glucose tolerance tests in both C57BL/6J mice and high-fat fed Zucker diabetic fatty rats.