1-benzoyl-3-(3-(benzyloxy)pyridin-2-yl)thiourea | 936246-98-9

• 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: 1-benzoyl-3-(3-(benzyloxy)pyridin-2-yl)thiourea
• 英文别名: 1-Benzoyl-3-(3-(benzyloxy)pyridin-2-yl)thiourea；N-[(3-phenylmethoxypyridin-2-yl)carbamothioyl]benzamide
• CAS: 936246-98-9
• 化学式: C₂₀H₁₇N₃O₂S
• 分子量: 363.44
• InChiKey: JJZWWGDYGRCYLL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  26
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.05
• 拓扑面积：
  95.3
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-benzoyl-3-(3-(benzyloxy)pyridin-2-yl)thiourea 在 potassium carbonate 、 三乙胺 作用下， 以 乙醇 为溶剂， 反应 9.0h， 生成 3-(benzyloxy)-N-(4-methylthiazol-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
• 作为产物：
  描述：

  2-氨基-3-苄氧基吡啶 、 苯甲酰基异硫氰酸酯 以 hexanes 、 四氢呋喃 为溶剂， 反应 2.0h， 以to afford 1-benzoyl-3-(3-(benzyloxy)pyridin-2-yl)thiourea (44.4 g, 97.9% yield) as a yellow solid的产率得到1-benzoyl-3-(3-(benzyloxy)pyridin-2-yl)thiourea
  参考文献：
  名称：

  Glucokinase activators

  摘要：

  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。

  公开号：

  US08933077B2

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。
• WO2007/53345
  申请人：——

  公开号：——

  公开（公告）日：——
• US8933077B2
  申请人：——

  公开号：US8933077B2

  公开（公告）日：2015-01-13
• [EN] GLUCOKINASE ACTIVATORS<br/>[FR] ACTIVATEURS DE GLUCOKINASE
  申请人：ARRAY BIOPHARMA INC

  公开号：WO2007053345A1

  公开（公告）日：2007-05-10

  [EN] 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.
  [FR] La présente invention concerne des composés de Formule I où R¹, R², Y, Z et G sont tels que définis dans l'invention, et pouvant être employés dans le traitement prophylactique et/ou thérapeutique de maladies faisant intervenir une activité glucokinase déficiente, comme le diabète sucré. La présente invention porte également sur des méthodes de traitement prophylactique ou thérapeutique de maladies et de troubles caractérisés par une sous-activité des glucokinases, ou pouvant être traités par l'activation des glucokinases.
• 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.