6-氨基-2-(吡啶-2-基)嘧啶-4(3h)-酮 | 264880-77-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 中文名称: 6-氨基-2-(吡啶-2-基)嘧啶-4(3h)-酮
• 英文名称: 6-hydroxy-2-(pyridin-2-yl)pyrimidin-4-amine
• 英文别名: 6-Amino-2-(pyridin-2-yl)pyrimidin-4(3H)-one；4-amino-2-pyridin-2-yl-1H-pyrimidin-6-one
• CAS: 264880-77-5
• 化学式: C₉H₈N₄O
• 分子量: 188.189
• InChiKey: GLIITTLXUIDKLK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.3
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  80.4
• 氢给体数：
  2
• 氢受体数：
  4

安全信息

• 海关编码：
  2933990090

反应信息

• 作为反应物：
  描述：

  6-氨基-2-(吡啶-2-基)嘧啶-4(3h)-酮 在 N,N-二异丙基乙胺 、 三氯氧磷 作用下， 生成 2-（2-吡啶基）-6-氯-4-氨基嘧啶
  参考文献：
  名称：

  2,6-Diaryl-4-phenacylaminopyrimidines as potent and selective adenosine A2A antagonists with reduced hERG liability

  摘要：

  In this report, the design and synthesis of a series of pyrimidine based adenosine A(2A) antagonists are described. The strategy and outcome of expanding SAR exploration to attenuate hERG and improve selectivity over A(1) are discussed. Compound 33 exhibited excellent potency, selectivity over A1, and reduced hERG liability. (c) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2008.01.036
• 作为产物：
  描述：

  2-脒基吡啶盐酸盐 、 氰乙酸乙酯 在 sodium methylate 作用下， 以 甲醇 、 乙醇 为溶剂， 反应 16.5h， 以18.1 g的产率得到6-氨基-2-(吡啶-2-基)嘧啶-4(3h)-酮
  参考文献：
  名称：

  2-Amino-N-pyrimidin-4-ylacetamides as A_2A Receptor Antagonists: 1. Structure−Activity Relationships and Optimization of Heterocyclic Substituents

  摘要：

  Previously we have described a novel series of potent and selective A(2A) receptor antagonists (e.g., 1) with excellent aqueous solubility.(1) While these compounds are efficacious A(2A) antagonists in vivo, the presence of an unsubstituted furyl moiety was a cause of some concern. In order to avoid the potential metabolic liabilities that could arise from an unsubstituted fury] moiety, an optimization effort was undertaken with the aim of replacing the unsubstituted furan with a more metabolically stable group while maintaining potency and selectivity. Herein, we describe the synthesis and SAR of a range of novel heterocyclic systems and the successful identification of a replacement for the unsubstituted furan moiety with a methylfuran or thiazole moiety while maintaining potency and selectivity.

  DOI：

  10.1021/jm701185v

文献信息

• Structure activity analysis of the pro-apoptotic, antitumor effect of nitrostyrene adducts and related compounds
  作者：Sylvia Kaap、Iris Quentin、Dereje Tamiru、Mohammed Shaheen、Kurt Eger、Hans Jürgen Steinfelder

  DOI：10.1016/s0006-2952(02)01618-0

  日期：2003.2

  ring of NS albeit with a 2-3-fold reduced potency. In conclusion, nitrostyrene was identified as the core structure mediating the pro-apoptotic effect of a new synthetic phosphatase inhibitor. Further studies defined a nitrovinyl side chain attached to an aromatic ring as the pharmacophore structure of a new group of pro-apoptotic agents. These observations present the basis for the development of a new

  在本研究中，我们概述了介导抗坏血酸的迈克尔加合物与新型合成磷酸酶抑制剂对氯硝基苯乙烯的突出促凋亡作用的分子部分。硝基苯乙烯（NS）部分被确定为细胞凋亡诱导必不可少的结构。NS及其抗坏血酸加合物显示10-25 microM的LC（50）值，在过表达MDR1 P-糖蛋白的冈田酸抗性细胞中效力没有显着降低。NS衍生物和蛋白磷酸酶2A抑制剂cantharidic酸诱导的细胞凋亡通过caspase-3激活和随后的DNA片段化分析得到证实。进一步的结构活性分析表明，在侧链的β-位需要硝基。NS与嘧啶或吡啶衍生物的加合物的促凋亡潜力在NS之间变化，并且效力逐渐降低直至几乎完全丧失细胞毒性。NS苯核心的取代表明，仅通过2位或3位取代可以显着提高毒性。杂环芳族化合物可以取代NS的苯环，尽管其效能降低了2至3倍。总之，硝基苯乙烯被确定为介导新型合成磷酸酶抑制剂促凋亡作用的核心结构。进一步的研究将与芳香环相连的
• 2,6 Bisheteroaryl-4-Aminopyrimidines as Adenosine Receptor Antagonists
  申请人：Crespo Crespo Maria Isabel

  公开号：US20080058356A1

  公开（公告）日：2008-03-06

  4-Aminopyrimidine derivatives of formula (I) FORMULA heteroaryl groups, including pharmaceutically acceptable salts thereof, wherein R 1 and R 2 are adenosine A 2A receptor antagonists useful in the treatment of movement disorders such as Parkinson's disease.

  公式（I）的4-氨基嘧啶衍生物，其中包括杂环基团，以及其药学上可接受的盐，其中R1和R2是阿多诺西嗪A2受体拮抗剂，适用于治疗运动障碍，如帕金森病。
• 2-Amino-<i>N</i>-pyrimidin-4-ylacetamides as A_2A Receptor Antagonists: 1. Structure−Activity Relationships and Optimization of Heterocyclic Substituents
  作者：Deborah H. Slee、Yongsheng Chen、Xiaohu Zhang、Manisha Moorjani、Marion C. Lanier、Emily Lin、Jaimie K. Rueter、John P. Williams、Sandra M. Lechner、Stacy Markison、Siobhan Malany、Mark Santos、Raymond S. Gross、Kayvon Jalali、Yang Sai、Zhiyang Zuo、Chun Yang、Julio C. Castro-Palomino、María I. Crespo、Maria Prat、Silvia Gual、José-Luis Díaz、John Saunders

  DOI：10.1021/jm701185v

  日期：2008.3.1

  Previously we have described a novel series of potent and selective A(2A) receptor antagonists (e.g., 1) with excellent aqueous solubility.(1) While these compounds are efficacious A(2A) antagonists in vivo, the presence of an unsubstituted furyl moiety was a cause of some concern. In order to avoid the potential metabolic liabilities that could arise from an unsubstituted fury] moiety, an optimization effort was undertaken with the aim of replacing the unsubstituted furan with a more metabolically stable group while maintaining potency and selectivity. Herein, we describe the synthesis and SAR of a range of novel heterocyclic systems and the successful identification of a replacement for the unsubstituted furan moiety with a methylfuran or thiazole moiety while maintaining potency and selectivity.
• 2,6-Diaryl-4-phenacylaminopyrimidines as potent and selective adenosine A2A antagonists with reduced hERG liability
  作者：Manisha Moorjani、Xiaohu Zhang、Yongsheng Chen、Emily Lin、Jaimie K. Rueter、Raymond S. Gross、Marion C. Lanier、John E. Tellew、John P. Williams、Sandra M. Lechner、Siobhan Malany、Mark Santos、Paddi Ekhlassi、Julio C. Castro-Palomino、Marı´a I. Crespo、Maria Prat、Silvia Gual、José-Luis Díaz、John Saunders、Deborah H. Slee

  DOI：10.1016/j.bmcl.2008.01.036

  日期：2008.2

  In this report, the design and synthesis of a series of pyrimidine based adenosine A(2A) antagonists are described. The strategy and outcome of expanding SAR exploration to attenuate hERG and improve selectivity over A(1) are discussed. Compound 33 exhibited excellent potency, selectivity over A1, and reduced hERG liability. (c) 2008 Elsevier Ltd. All rights reserved.