6-chloro-2-(methylthio)-N-(pyrazin-2-yl)pyrimidin-4-amine | 1522207-04-0

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫醚类
• 英文名称: 6-chloro-2-(methylthio)-N-(pyrazin-2-yl)pyrimidin-4-amine
• 英文别名: 6-chloro-2-methylsulfanyl-N-pyrazin-2-ylpyrimidin-4-amine
• CAS: 1522207-04-0
• 化学式: C₉H₈ClN₅S
• 分子量: 253.715
• InChiKey: WXEZUYTYFQHIPK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  88.9
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  6-chloro-2-(methylthio)-N-(pyrazin-2-yl)pyrimidin-4-amine 在 Oxone 、 sodium hydride 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 28.0h， 生成 [2-(3,5-dimethylpyrazol-1-yl)-6-((R)-2-methoxymethylpyrrolidin-1-yl)pyrimidin-4-yl]pyrazin-2-ylamine
  参考文献：
  名称：

  Replacement of amide with bioisosteres led to a new series of potent adenosine A2A receptor antagonists

  摘要：

  We have previously reported a series of 2,4,6-trisubstituted pyrimidines as potent A(2A) receptor antagonists. The leading compounds often feature a potentially labile acetamide functional group which tends to hydrolyze under acidic conditions. Here we report the replacement of the acetamide functional group with bioisosteres. This effort led us to a new series of adenosine A(2A) receptor antagonists with improved potency and chemical stability. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.11.051
• 作为产物：
  描述：

  氨基吡嗪 、 4,6-二氯-二甲硫基嘧啶 在 sodium hexamethyldisilazane 作用下， 以 四氢呋喃 为溶剂， 反应 8.0h， 以80%的产率得到6-chloro-2-(methylthio)-N-(pyrazin-2-yl)pyrimidin-4-amine
  参考文献：
  名称：

  Optimization of 6-Heterocyclic-2-(1H-pyrazol-1-yl)-N-(pyridin-2-yl)pyrimidin-4-amine as Potent Adenosine A_2A Receptor Antagonists for the Treatment of Parkinson’s Disease

  摘要：

  Parkinson's disease is a neurodegenerative disease characterized by the motor symptoms of bradykinesia, tremor, and rigidity. Current therapies are based mainly on dopaminergic replacement strategies by administration of either dopamine agonists or dopamine precursor levodopa (L-Dopa). These treatments provide symptomatic relief without slowing or stopping the disease progression, and long-term usage of these drugs is associated with diminished efficacy, motor fluctuation, and dyskinisia. Unfortunately, there had been few novel treatments developed in the past decades. Among nondopaminergic strategies for the treatment of Parkinson's disease, antagonism of the adenosine A2A receptor has emerged to show great potential. Here we report the optimization of a new chemical scaffold, which achieved exceptional receptor binding affinity and ligand efficiency against adenosine A2A receptor. The leading compounds demonstrated excellent efficacy in the haloperidol induced catalepsy model for Parkinson's disease.

  DOI：

  10.1021/cn5000716

文献信息

• Replacement of amide with bioisosteres led to a new series of potent adenosine A2A receptor antagonists
  作者：Zhaohui Yang、Xuan Li、Haikuo Ma、Jiyue Zheng、Xuechu Zhen、Xiaohu Zhang

  DOI：10.1016/j.bmcl.2013.11.051

  日期：2014.1

  We have previously reported a series of 2,4,6-trisubstituted pyrimidines as potent A(2A) receptor antagonists. The leading compounds often feature a potentially labile acetamide functional group which tends to hydrolyze under acidic conditions. Here we report the replacement of the acetamide functional group with bioisosteres. This effort led us to a new series of adenosine A(2A) receptor antagonists with improved potency and chemical stability. (C) 2013 Elsevier Ltd. All rights reserved.
• Optimization of 6-Heterocyclic-2-(1<i>H</i>-pyrazol-1-yl)-<i>N</i>-(pyridin-2-yl)pyrimidin-4-amine as Potent Adenosine A_2A Receptor Antagonists for the Treatment of Parkinson’s Disease
  作者：Jiyue Zheng、Zhaohui Yang、Xuan Li、Linlang Li、Haikuo Ma、Meiyu Wang、Hongjian Zhang、Xuechu Zhen、Xiaohu Zhang

  DOI：10.1021/cn5000716

  日期：2014.8.20

  Parkinson's disease is a neurodegenerative disease characterized by the motor symptoms of bradykinesia, tremor, and rigidity. Current therapies are based mainly on dopaminergic replacement strategies by administration of either dopamine agonists or dopamine precursor levodopa (L-Dopa). These treatments provide symptomatic relief without slowing or stopping the disease progression, and long-term usage of these drugs is associated with diminished efficacy, motor fluctuation, and dyskinisia. Unfortunately, there had been few novel treatments developed in the past decades. Among nondopaminergic strategies for the treatment of Parkinson's disease, antagonism of the adenosine A2A receptor has emerged to show great potential. Here we report the optimization of a new chemical scaffold, which achieved exceptional receptor binding affinity and ligand efficiency against adenosine A2A receptor. The leading compounds demonstrated excellent efficacy in the haloperidol induced catalepsy model for Parkinson's disease.