N-(6-chloro-2-(methylthio)pyrimidin-4-yl)thiazol-2-amine | 929568-21-8

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫醚类
• 英文名称: N-(6-chloro-2-(methylthio)pyrimidin-4-yl)thiazol-2-amine
• 英文别名: 6-chloro-2-methylthio-4-(thiazol-2-ylamino)pyrimidine；N-(6-chloro-2-methylsulfanylpyrimidin-4-yl)-1,3-thiazol-2-amine
• CAS: 929568-21-8
• 化学式: C₈H₇ClN₄S₂
• 分子量: 258.755
• InChiKey: LDCHANSHRXUPHE-UHFFFAOYSA-N

物化性质

• 沸点：
  416.7±55.0 °C(Predicted)
• 密度：
  1.53±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  15
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  104
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  N-(6-chloro-2-(methylthio)pyrimidin-4-yl)thiazol-2-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 (R)-N-(6-(2-(methoxymethyl)pyrrolidin-1-yl)-2-(1H-pyrazol-1-yl)pyrimidin-4-yl)thiazol-2-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
• 作为产物：
  描述：

  2-氨基噻唑 、 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， 生成 N-(6-chloro-2-(methylthio)pyrimidin-4-yl)thiazol-2-amine
  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

文献信息

• PYRIMIDINE DERIVATIVES FOR THE INHIBITION OF IGF-IR TYROSINE KINASE ACTIVITY
  申请人：Thomas Andrew Peter

  公开号：US20090306116A1

  公开（公告）日：2009-12-10

  A compound of formula (I) wherein the substituents are as defined in the text for use in inhibiting insulin-like growth factor 1 receptor activity in a warm blooded animal such as man.

  公式（I）的化合物，其中取代基如文本中定义的那样，用于抑制温血动物（如人）中胰岛素样生长因子1受体活性。
• WO2007/31745
  申请人：——

  公开号：——

  公开（公告）日：——
• 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.
• [EN] PYRIMIDINE DERIVATIVES FOR THE INHIBITION OF IGF-IR TYROSINE KINASE ACTIVITY<br/>[FR] DÉRIVÉS DE LA PYRIMIDINE UTILISÉS POUR INHIBER L'ACTIVITÉ DE LA TYROSINE KINASE IGF-IR
  申请人：ASTRAZENECA AB

  公开号：WO2007031745A1

  公开（公告）日：2007-03-22

  [EN] A compound of formula (I) wherein the substituents are as defined in the text for use in inhibiting insulin-like growth factor 1 receptor activity in a warm blooded animal such as man.
  [FR] La présente invention concerne un composé de formule (I) dans lequel les substituants sont tels que définis dans la description, qui est utilisé en vue d'inhiber l'activité des récepteurs du facteur de croissance analogue à l'insuline de type I chez un animal à sang chaud tel que l'homme.
• 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.