ethyl N-((Z)-2-amino-1,2-dicyanovinyl)formimidate

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 甲亚胺酸及其衍生物
• 英文名称: ethyl N-((Z)-2-amino-1,2-dicyanovinyl)formimidate
• 英文别名: ethyl N-[(Z)-2-amino-1,2-dicyanoethenyl]methanimidate
• 化学式: C₇H₈N₄O
• 分子量: 164.167
• InChiKey: WAKHKSLIDJTOKC-VEAKALIJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.1
• 重原子数：
  12
• 可旋转键数：
  3
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  95.2
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  ethyl N-((Z)-2-amino-1,2-dicyanovinyl)formimidate 在 aniline hydrochloride 作用下， 以 乙醇 为溶剂， 反应 18.0h， 生成 9-[(2,6-Difluorophenyl)methyl]purine-6-carbonitrile
  参考文献：
  名称：

  Facile synthesis of 6-cyano-9-substituted-9H-purines and their ring expansion to 8-(arylamino)-4-imino-3-methylpyrimidino[5,4-d]pyrimidines

  摘要：

  6-氰基-9-取代-9H-嘌呤通过将三乙基正形酸酯或三乙基正丙酸酯与相应的(Z)-N1-(芳基或苄基)-N2-(2-氨基-1,2-二氰基乙烯)氨基甲酰胺在回流条件下反应制备，反应产率较高。这些氰基嘌呤与水合的甲胺反应时，生成了8-(芳氨基)-4-亚氨基-3-甲基吡啶并[5,4-d]吡啶，反应发生在咪唑环上，而不是对6-氰基进行加成。所有化合物均已通过光谱数据得到全面表征，并对8-(4-甲氧基苯胺基)-4-亚氨基-3-甲基吡啶并[5,4-d]吡啶进行了X射线晶体结构的测定。

  DOI：

  10.1039/b106539b
• 作为产物：
  描述：

  原甲酸三乙酯 以 乙醇 为溶剂， 以44.6%的产率得到ethyl N-((Z)-2-amino-1,2-dicyanovinyl)formimidate
  参考文献：
  名称：

  PROCESSES FOR THE PREPARATION OF 4(5)-AMINO-5(4)-CARBOXAMIDOIMIDAZOLES AND INTERMEDIATES THEREOF

  摘要：

  公开号：

  EP1215206B1

文献信息

• Anticancer potential of some imidazole and fused imidazole derivatives: exploring the mechanism <i>via</i> epidermal growth factor receptor (EGFR) inhibition
  作者：Sourav Kalra、Gaurav Joshi、Manvendra Kumar、Sahil Arora、Harsimrat Kaur、Sandeep Singh、Anjana Munshi、Raj Kumar

  DOI：10.1039/d0md00146e

  日期：——

  Imidazole-based epidermal growth factor receptor (EGFR) inhibitors were computationally designed and synthesized. All the compounds were assessed for their anti-proliferative activity against five cancer cell lines, viz., MDA-MB-231 (breast), T47D (breast) and MCF-7 (breast), A549 (lung) and HT-29 (colorectal). Compounds 2c and 2d emerged as better anticancer molecules with no toxicity towards normal

  基于咪唑的表皮生长因子受体 (EGFR) 抑制剂是通过计算设计和合成的。评估了所有化合物对五种癌细胞系的抗增殖活性，即。、MDA-MB-231（乳房）、T47D（乳房）和 MCF-7（乳房）、A549（肺）和 HT-29（结肠直肠）。化合物2c和2d成为更好的抗癌分子，对正常细胞没有毒性。2c和2d在体外抑制EGFR酶活性，IC 50值分别为617.33 ± 0.04 nM和710 ± 0.05 nM。为了进一步提高效力，我们探索了EGFR的ATP结合域的一个未被占用的区域并对其进行了分析2c和2d -EGFR 配合物的计算机相互作用模型，该模型引导并允许在 N-9 位置用 4-(4-甲基哌嗪基)-3-硝基苯基取代 4-氟苯基环（2c和2d ），得到化合物3c具有更好的结合评分和有效的 EGFR 抑制活性 (IC 50 : 236.38 ± 0.04 nM)，与阳性对照厄洛替尼 (239.91
• New application of heterocyclic diazonium salts. Synthesis of pyrazolo[3,4-d][1,2,3]triazin-4-ones and imidazo[4,5-d][1,2,3]triazin-4-ones
  作者：Juan Pablo Colomer、Elizabeth Laura Moyano

  DOI：10.1016/j.tetlet.2011.01.040

  日期：2011.4

  The pyrazolo[3,4-d][1,2,3]triazin-4-ones 3 and imidazo[4,5-d][1,2,3]triazin-4-ones 4 are analogs structurally related to purines that have showed a wide and significant variety of biological activity. These compounds were synthesized by one-pot diazotization of 5-amino-1H-pyrazole-4-carbonitriles 1 and 5-amino-1H-imidazole-4-carbonitriles 2, respectively.

  吡唑并[3,4- d ] [1,2,3] triazin-4-ones 3和咪唑并[4,5- d ] [1,2,3] triazin-4-ones 4是与嘌呤在结构上相关的类似物表现出广泛而显着的生物活性。这些化合物分别通过一锅重氮化5-氨基-1 H-吡唑-4-腈1和5-氨基-1 H-咪唑-4-腈2合成。
• [EN] DERIVATIVES OF ADENINE AND 8-AZA-ADENINE AND USES THEREOF-796<br/>[FR] DÉRIVÉS DE L'ADÉNINE ET DE LA 8-AZA-ADÉNINE ET LEURS UTILISATIONS
  申请人：ASTRAZENECA AB

  公开号：WO2009034386A1

  公开（公告）日：2009-03-19

  The invention relates to chemical compounds, or pharmaceutically acceptable salts thereof of the formula (I): which have bacterial MurI inhibitory activity and are accordingly useful for their treatment and prophylaxis of bacterial infection, e.g., E.faecalis or E. faeciuminfection. Further, the invention relates to methods of treatment of the human or animal body. The invention also relates to processes for the manufacture of the compounds, to pharmaceutical compositions containing them, and to their use in the manufacture of medicaments of use in the treatment and prevention of various bacterial diseases in a warm-blooded animalsuch as man.

  该发明涉及化合物或其药用可接受的盐，其化学式为（I）：具有细菌MurI抑制活性，因此可用于治疗和预防细菌感染，例如E.faecalis或E. faecium感染。此外，该发明涉及人体或动物体的治疗方法。该发明还涉及化合物的制造方法，含有这些化合物的药物组合物，以及它们在制造用于治疗和预防人类等恒温动物各种细菌疾病的药物中的应用。
• Synthesis of Novel 6-Cyano-9-(aryl)-9<i>H</i>-purine Derivatives Via Formamidine Intermediates
  作者：Hashemi Seyyed Milad、Yahyazadeh Asieh、Nami Navabeh

  DOI：10.1155/2012/762641

  日期：——

  Novel 9-substituted cyanopurine derivatives (4a-d) were synthesized in three steps in high yield. Diaminomaleonitrile (1) reacted with triethyl orthoformate to afford (Z)-N-[2-amino-1,2-dicyanovinyl] formimidate (2) which was converted to aryl-(Z)-N-[2-amino-1,2-dicyanovinyl] formamidines (3a-d) in the presence of a catalytic amount of anilinium chloride and aromatic amines in ethanol at room temperature under inert atmosphere (Argon). Furthermore, the reaction of (3a-d) with triethyl orthoformate afforded novel 6-cyano-9-(aryl)-9H-purine derivatives (4a-d) which can be used without further purification. All compounds have been fully characterized by spectroscopic data.

  新型的9-取代氰基嘌呤衍生物（4a-d）在高产率下通过三步合成。二氨基丙二腈（1）与三乙基正甲酸酯反应，得到（Z）-N-[2-氨基-1,2-二氰乙烯基]甲酰胺（2），然后在乙醇中在惰性气氛（氩气）下存在少量阿酰氯和芳香胺的情况下，将其转化为芳基-(Z)-N-[2-氨基-1,2-二氰乙烯基]甲酰胺（3a-d）。此外，（3a-d）与三乙基正甲酸酯的反应得到新型的6-氰基-9-(芳基)-9H-嘌呤衍生物（4a-d），可以直接使用而无需进一步纯化。所有化合物均通过光谱数据进行了全面表征。
• Imine/amide–imidazole conjugates derived from 5-amino-4-cyano- N 1-substituted benzyl imidazole: Microwave-assisted synthesis and anticancer activity via selective topoisomerase-II-α inhibition
  作者：Arvind Negi、Jimi Marin Alex、Suyog M. Amrutkar、Ashish T. Baviskar、Gaurav Joshi、Sandeep Singh、Uttam C. Banerjee、Raj Kumar

  DOI：10.1016/j.bmc.2015.07.020

  日期：2015.9

  Microwave-accelerated synthesis and anticancer activity of novel imine/ amide-imidazole conjugates derived from 5-amino-4-cyano-N1-substituted benzyl imidazole against a panel of seven cancer cell lines are reported for the first time. Compounds ARK-4, 10 and 12 in the series show promising in vitro anti proliferative activity with low micromolar IC50 values against A-459 (lung), Hep-G2 (liver) and H-460 (liver) cancer cell lines. Compounds caused the increase in ROS levels as well as mitochondrial membrane depolarization, which might induce apoptosis. Further, mechanistic interventions on biological and molecular modeling data supported that compounds inhibited topoisomerase-II selectively. (C) 2015 Elsevier Ltd. All rights reserved.