2-hydroxy-N-(4-methyl-1,3-thiazol-2-yl)hexanamide | 1207831-17-1

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: 2-hydroxy-N-(4-methyl-1,3-thiazol-2-yl)hexanamide
• CAS: 1207831-17-1
• 化学式: C₁₀H₁₆N₂O₂S
• 分子量: 228.315
• InChiKey: UOAAUXJRNFLKNS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  15
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  90.5
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-氯-1-(2-氯苯基)-1H-吡唑并[3,4-d]嘧啶 、 2-hydroxy-N-(4-methyl-1,3-thiazol-2-yl)hexanamide 在 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 为溶剂， 生成 2-{[1-(2-chlorophenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl]oxy}-N-(4-methyl-1,3-thiazol-2-yl)hexanamide
  参考文献：
  名称：

  The discovery of a novel series of glucokinase activators based on a pyrazolopyrimidine scaffold

  摘要：

  Glucokinase is a key enzyme in glucose homeostasis since it phosphorylates glucose to give glucose-6-phosphate, which is the first step in glycolysis. GK activators have been proven to lower blood-glucose, and therefore have potential as treatments for type 2 diabetes. Here the discovery of pyrazolopyrimidine GKAs is reported. An original singleton hit from a high-throughput screen with micromolar levels of potency was optimised to give compounds with nanomolar activities. Key steps in this success were the introduction of an extra side-chain, which increased potency, and changing the linking functionality from a thioether to an ether, which led to improved potency and lipophilic ligand efficiency. This also led to more stable compounds with improved profiles in biological assays. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.10.090
• 作为产物：
  描述：

  、 ethyl 2-((tert-butyldimethylsilyl)oxy)hexanoate 、 2-氨基-4-甲基噻唑 生成 2-hydroxy-N-(4-methyl-1,3-thiazol-2-yl)hexanamide
  参考文献：
  名称：

  THERAPEUTIC AGENTS 414

  摘要：

  化合物式（I）的复合物在治疗或预防通过葡萄糖激酶（GLK或GK）介导的疾病或医疗状况中非常有用，从而导致胰岛素分泌的葡萄糖阈值降低。

  公开号：

  US20100093757A1

文献信息

• THERAPEUTIC AGENTS 414
  申请人：BENNETT Stuart Norman Lile

  公开号：US20100093757A1

  公开（公告）日：2010-04-15

  A compound of Formula (I): is useful in the treatment or prevention of a disease or medical condition mediated through glucokinase (GLK or GK), leading to a decreased glucose threshold for insulin secretion.

  化合物Formula (I)在通过葡萄糖激酶（GLK或GK）介导的疾病或医疗状况的治疗或预防中很有用，导致胰岛素分泌的葡萄糖阈值降低。
• US8143263B2
  申请人：——

  公开号：US8143263B2

  公开（公告）日：2012-03-27
• [EN] THERAPEUTIC AGENTS 414<br/>[FR] AGENTS THÉRAPEUTIQUES 414
  申请人：ASTRAZENECA AB

  公开号：WO2010015849A2

  公开（公告）日：2010-02-11

  A compound of Formula (I) is useful in the treatment or prevention of a disease or medical condition mediated through glucokinase (GLK or GK), leading to a decreased glucose threshold for insulin secretion.
• The discovery of a novel series of glucokinase activators based on a pyrazolopyrimidine scaffold
  作者：Peter Bonn、D. Mikael Brink、Jonas Fägerhag、Ulrik Jurva、Graeme R. Robb、Volker Schnecke、Anette Svensson Henriksson、Michael J. Waring、Christer Westerlund

  DOI：10.1016/j.bmcl.2012.10.090

  日期：2012.12

  Glucokinase is a key enzyme in glucose homeostasis since it phosphorylates glucose to give glucose-6-phosphate, which is the first step in glycolysis. GK activators have been proven to lower blood-glucose, and therefore have potential as treatments for type 2 diabetes. Here the discovery of pyrazolopyrimidine GKAs is reported. An original singleton hit from a high-throughput screen with micromolar levels of potency was optimised to give compounds with nanomolar activities. Key steps in this success were the introduction of an extra side-chain, which increased potency, and changing the linking functionality from a thioether to an ether, which led to improved potency and lipophilic ligand efficiency. This also led to more stable compounds with improved profiles in biological assays. (C) 2012 Elsevier Ltd. All rights reserved.
• Therapeutic agents
  申请人：Astrazeneca AB

  公开号：US08143263B2

  公开（公告）日：2012-03-27

  A compound of Formula (I): is useful in the treatment or prevention of a disease or medical condition mediated through glucokinase (GLK or GK), leading to a decreased glucose threshold for insulin secretion.

  公式（I）的化合物可用于治疗或预防通过葡萄糖激酶（GLK或GK）介导的疾病或医疗状况，从而导致胰岛素分泌的葡萄糖阈值降低。