4-cyano-3-[(ethoxymethylene)amino]-1-methylpyrazole | 159979-75-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 4-cyano-3-[(ethoxymethylene)amino]-1-methylpyrazole
• 英文别名: ethyl N-(4-cyano-1-methylpyrazol-3-yl)methanimidate
• CAS: 159979-75-6
• 化学式: C₈H₁₀N₄O
• 分子量: 178.194
• InChiKey: DWBRWBHACYJKFX-UHFFFAOYSA-N

物化性质

• 熔点：
  51-52 °C(Solv: ethyl acetate (141-78-6); hexane (110-54-3))
• 沸点：
  349.4±27.0 °C(Predicted)
• 密度：
  1.15±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  13
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  63.2
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-cyano-3-[(ethoxymethylene)amino]-1-methylpyrazole 在 肼 作用下， 以 乙醇 为溶剂， 以96 %的产率得到5-amino-4-imino-2-methyl-2H-4,5-dihydropyrazolo[3,4-d]pyrimidine
  参考文献：
  名称：

  前所未有的 14 元六氮杂大环合成

  摘要：

  摘要 3-[(乙氧基亚甲基)氨基]-1-甲基-1H-吡唑-4-甲腈转化为14元大环2,10-二甲基-2,8,10,16-四氢二吡唑[3,4 -e : 3',4'- l ][1,2,4,8,9,11]六氮杂环十四胺-4,12-二胺在各种条件下与过量肼反应进行了详细研究。该反应首先形成4-亚氨基-2-甲基-2,4-二氢-5H-吡唑并[3,4- d ]嘧啶-5-胺，然后二聚得到最终的大环。开发了一种以 4-亚氨基-2-甲基-2,4-二氢-5 H-吡唑并[3,4- d ]嘧啶-5-胺为原料的便捷合成方法。讨论了大环自组装的合理途径。概述了所获得的大环的结构和反应性的一些特征。 贝尔斯坦 J. 组织。化学。 2023, 19, 1728–1740。doi:10.3762/bjoc.19.126

  DOI：

  10.3762/bjoc.19.126
• 作为产物：
  描述：

  3-[(2E)-2-benzylidene-1-methylhydrazino]-2-isocyanoacrylonitrile 在 盐酸 作用下， 以 乙醇 、 水 为溶剂， 反应 21.0h， 生成 4-cyano-3-[(ethoxymethylene)amino]-1-methylpyrazole
  参考文献：
  名称：

  One-Pot Reaction To Obtain N,N′-Disubstituted Guanidines of Pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidine Scaffold as Human A₃ Adenosine Receptor Antagonists

  摘要：

  In this paper we describe an extension SAR study of pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidine nucleus as A(3)AR antagonist. Our initial aim was to replace the phenylcarbamoyl moiety at the 5 position of PTP nucleus with a thiourea functionality to evaluate the contribution of new structural modification against the A(3)AR. The synthesized 12-25 were not characterized by the predicted side chain but by a 1,3-disubstituted guanidine and are shown to be interesting A(3)AR antagonists.

  DOI：

  10.1021/acs.jmedchem.5b00551

文献信息

• Organoruthenium Antagonists of Human A₃Adenosine Receptors
  作者：Priyankar Paira、Mun Juinn Chow、Gopalakrishnan Venkatesan、Vamsi Krishna Kosaraju、Siew Lee Cheong、Karl-Norbert Klotz、Wee Han Ang、Giorgia Pastorin

  DOI：10.1002/chem.201203291

  日期：2013.6.17

  triazolo moiety with an organoruthenium fragment. The objective was to introduce by design structural diversity into the PTP scaffold in order to tune their binding efficacy toward the target receptor. These novel organoruthenium antagonists displayed good aquatic stability and moderate binding affinity toward the hA3 receptor in the low micromolar range. The assembly of these complexes through a template‐driven

  人A 3腺苷受体（hA 3 AR）是膜结合的G蛋白偶联受体，与许多严重的病理状况（包括癌症）有关，在其中它可能成为潜在的治疗靶标。为了推导基于吡唑并三唑并嘧啶（PTP）的A 3 AR拮抗剂的构效关系，我们通过用有机钌片段代替三唑并开发了新型的有机金属抑制剂。目的是通过设计将结构多样性引入PTP支架中，以调节其对靶受体的结合功效。这些新型的有机钌拮抗剂显示出良好的水生稳定性和对hA 3的中等结合亲和力受体在低微摩尔范围内。讨论了通过模板驱动的方法组装这些复合物，并在金属中心进行选择性配体置换以控制其空间和受体结合特性的方法。
• A new synthesis of 2,8-disubstituted pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidines
  作者：Anton V. Dolzhenko、Giorgia Pastorin、Anna V. Dolzhenko、Wai Keung Chui

  DOI：10.1016/j.tetlet.2009.07.113

  日期：2009.10

  5-c]pyrimidines, which are key intermediates in the preparation of adenosine receptor antagonists, is developed. The method allows introduction of a variety of aryl substituents at position 2 of the pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidine system via cyclocondensation of 5-amino-4-iminopyrazolo[3,4-d]pyrimidine with benzaldehydes accompanied with oxidation by iodobenzene diacetate. Some unexpected

  开发了实用的吡唑并[4,3- e ] [1,2,4]三唑并[1,5- c ]嘧啶的合成方法，它们是制备腺苷受体拮抗剂的关键中间体。该方法允许通过5-氨基-4-亚氨基吡唑并环缩合在吡唑并[4,3- e ] [1,2,4]三唑并[1,5- c ]嘧啶体系的2位引入各种芳基取代基。[3,4- d ]嘧啶与苯甲醛并伴随有碘代二苯乙酸酯的氧化。观察到一些意想不到的反应，并使用NMR光谱和X射线晶体学证实了产物的结构。
• Does the combination of optimal substitutions at the C2-, N5- and N8-positions of the pyrazolo-triazolo-pyrimidine scaffold guarantee selective modulation of the human A3 adenosine receptors?
  作者：Siew Lee Cheong、Anton V. Dolzhenko、Silvia Paoletta、Evelyn Pei Rong Lee、Sonja Kachler、Stephanie Federico、Karl-Norbert Klotz、Anna V. Dolzhenko、Giampiero Spalluto、Stefano Moro、Giorgia Pastorin

  DOI：10.1016/j.bmc.2011.08.026

  日期：2011.10

  In an attempt to study the optimal combination of a phenyl ring at the C-2-position and different substituents at the N-5- and N-8-positions towards the selective modulation of human A(3) adenosine receptors (hA(3)AR), we synthesized a new series of 2-para-(un)substituted-phenyl-pyrazolo-triazolo-pyrimidines bearing either a methyl or phenylethyl at N-8 and chains of variable length at N-5. Through biological evaluation, it was found that the majority of the compounds had good affinities towards the hA(3)AR in the low nanomolar range. Compound 16 possessed the best hA(3)AR affinity and selectivity profile (K(i)hA(3) = 1.33 nM; hA(1)/hA(3) = 4880; hA(2A)/hA(3) = 1100) in the present series of2-(substituted)phenylpyrazolo-triazolo-pyrimidine derivatives. In addition to pharmacological characterization, a molecular modeling investigation on these compounds further elucidated the effect of different substituents at the pyrazolo-triazolo-pyrimidine scaffold on affinity and selectivity to hA3AR. (C) 2011 Elsevier Ltd. All rights reserved.
• The Significance of 2-Furyl Ring Substitution with a 2-(<i>para</i>-substituted) Aryl Group in a New Series of Pyrazolo-triazolo-pyrimidines as Potent and Highly Selective hA₃ Adenosine Receptors Antagonists: New Insights into Structure−Affinity Relationship and Receptor−Antagonist Recognition
  作者：Siew Lee Cheong、Anna Dolzhenko、Sonja Kachler、Silvia Paoletta、Stephanie Federico、Barbara Cacciari、Anton Dolzhenko、Karl-Norbert Klotz、Stefano Moro、Giampiero Spalluto、Giorgia Pastorin

  DOI：10.1021/jm100049f

  日期：2010.4.22

  Among the heterocyclic structures identified as potent human A(3) (hA(3)) adenosine receptor's antagonists, we have demonstrated that the new pyrazolo-triazolo-pyrimidines, bearing an aryl group in replacement of the C-2-furyl ring, not only confer a good pharmacological profile (with significantly enhanced selectivity against other adenosine receptor subytpes) but also overcome the metabolic transformation of the furan ring into toxic intermediates. All the synthesized [2-(para-substituted) phenyl]-pyrazolo-triazolo-pyrimidines showed affinity at the hA(3) receptor in the low nanomolar range. The most potent derivative of the series presented better affinity and excellent selectivity (compound 31, K-i hA(3) = 0.108 nM; hA(1)/hA(3) = 5200; hA(2A)/hA(3) = 7200), in comparison to the C-2-furyl counterpart. A receptor-driven molecular modeling investigation, based on a recently proposed model of A(3) receptor derived from the crystallographic structure of human A(2A) receptor, has been carried out in order to support the experimental binding data and to justify the enhanced selectivity against the other receptor subtypes.