2-bromo-N-pyrimidin-2-ylacetamide | 1343998-07-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 2-bromo-N-pyrimidin-2-ylacetamide
• CAS: 1343998-07-1
• 化学式: C₆H₆BrN₃O
• 分子量: 216.037
• InChiKey: SZOSITPPDUUYTQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0
• 重原子数：
  11
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  54.9
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-(2-chlorophenyl)-1H-pyrazolo[3,4-d]pyrimidine-4-thiol 、 2-bromo-N-pyrimidin-2-ylacetamide 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 2-[1-(2-chlorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]sulfanyl-N-pyrimidin-2-ylacetamide
  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：

  1,3,5-三嗪-2,4,6-三胺,N,N'''-1,2-乙二基二[N-[3-[[4,6-二[丁基(2,2,6,6-四甲基-4-哌啶基)氨基]-1,3,5-三嗪-2-基]氨基]丙基]-N,N''-二丁基-N,N''-二(2,2,6,6-四甲基-4-哌啶基)- 、 溴乙酰氯 在 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 生成 2-bromo-N-pyrimidin-2-ylacetamide
  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

文献信息

• Small Molecules Targeting Mycobacterium tuberculosis Type II NADH Dehydrogenase Exhibit Antimycobacterial Activity
  作者：Michael B. Harbut、Baiyuan Yang、Renhe Liu、Takahiro Yano、Catherine Vilchèze、Bo Cheng、Jonathan Lockner、Hui Guo、Chenguang Yu、Scott G Franzblau、H. Mike Petrassi、William R. Jacobs、Harvey Rubin、Arnab K. Chatterjee、Feng Wang

  DOI：10.1002/anie.201800260

  日期：2018.3.19

  phosphorylation is an essential metabolic function for Mycobaterium tuberculosis (Mtb), regardless of the growth environment. The type II NADH dehydrogenase (Ndh‐2) is the conduit for electrons into the pathway, and is absent in the mammalian genome, thus making it a potential drug target. Herein, we report the identification of two types of small molecules as selective inhibitors for Ndh‐2 through a multicomponent

  无论生长环境如何，通过氧化磷酸化产生ATP都是结核分枝杆菌（Mtb）必不可少的代谢功能。II型NADH脱氢酶（Ndh-2）是电子进入途径的通道，在哺乳动物基因组中不存在，因此使其成为潜在的药物靶标。本文中，我们报告了通过多组分高通量筛选鉴定出两种类型的小分子作为Ndh-2的选择性抑制剂。两种化合物均会阻止ATP的合成，产生与NADH转化损失相一致的效果，并且重要的是，它对Mtb具有杀菌活性。广泛药物化学优化，得到最好的类似物具有90-n的MIC米针对山地车。此外，这两种支架对Mtb中的两种同源Ndh-2酶具有不同的抑制活性，这将允许精确控制Mtb中的Ndh-2功能，从而有助于评估该抗结核药物靶标。
• 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.