2-pyrazineisocyanate | 72975-45-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 2-pyrazineisocyanate
• 英文别名: Pyrazine, 2-isocyanato-；2-isocyanatopyrazine
• CAS: 72975-45-2
• 化学式: C₅H₃N₃O
• 分子量: 121.098
• InChiKey: XGMWRDZMBPVHHQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  9
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  55.2
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-苯基-4-甲基-1-戊炔-3醇 、 2-pyrazineisocyanate 在 三乙胺 作用下， 以 甲苯 为溶剂， 反应 36.0h， 生成 4-methyl-1-phenylpent-1-yn-3-yl pyrazin-2-ylcarbamate
  参考文献：
  名称：

  咪唑键合的N-杂芳族化合物通过C-N键形成的自由基级联反应的电化学合成

  摘要：

  我们已开发出一种通过杂芳基胺与束缚的内部炔烃的区域特异性电化学（3 + 2）环化反应制备各种咪唑并合的N-杂芳族化合物的统一策略。电合成采用新型的四芳基肼作为催化剂，具有广泛的底物范围，并且不需要过渡金属催化剂和氧化剂。

  DOI：

  10.1002/anie.201711876
• 作为产物：
  描述：

  2-甲酸吡嗪 在 叠氮磷酸二苯酯 、 三乙胺 作用下， 以 苯 为溶剂， 反应 2.75h， 生成 2-pyrazineisocyanate
  参考文献：
  名称：

  基于四氢异喹啉的二芳基尿素衍生物的设计，合成和生物学评估，用于抑制VEGFR-2信号传导。

  摘要：

  结合二芳基脲部分的新型基于四氢异喹啉的化合物的结构系列被设计，合成，并通过生物学方法评估为VEFGR-2信号的抑制剂。结果，化合物9k和9s对吉非替尼对被测试的三种细胞系，包括A549，MCF-7和PC-3，表现出与吉非替尼相当或更高的细胞毒性。重要的是，它们两个都下调了VEGFR-2的表达，并以0.5或1.0μmol/ l的浓度抑制了VEGFR-2的磷酸化。此外，它们以4.0μmol/ l的浓度抑制人脐静脉内皮细胞管的形成。考虑到它们下调VEGFR-2表达和抑制VEGFR-2磷酸化的能力，9k和9s可以作为血管生成的抑制剂，以供进一步研究。

  DOI：

  10.1097/cad.0000000000000718

文献信息

• AMIDE COMPOUND
  申请人：KORI Masakuni

  公开号：US20090163508A1

  公开（公告）日：2009-06-25

  An object of the present invention is to provide a novel fused-ring compound which has a FAAH inhibitory effect and is useful as an analgesic. The present invention relates to a compound represented by formula (I): wherein symbols are as defined in the specification, or salt thereof.

  本发明的一个目的是提供一种具有FAAH抑制作用并且作为镇痛药物有用的新型融环化合物。本发明涉及一种由下式表示的化合物： 其中符号如规范中定义的，或其盐。
• Synthetic group A streptogramin antibiotics that overcome Vat resistance
  作者：Qi Li、Jenna Pellegrino、D. John Lee、Arthur A. Tran、Hector A. Chaires、Ruoxi Wang、Jesslyn E. Park、Kaijie Ji、David Chow、Na Zhang、Axel F. Brilot、Justin T. Biel、Gydo van Zundert、Kenneth Borrelli、Dean Shinabarger、Cindy Wolfe、Beverly Murray、Matthew P. Jacobson、Estelle Mühle、Olivier Chesneau、James S. Fraser、Ian B. Seiple

  DOI：10.1038/s41586-020-2761-3

  日期：2020.10.1

  group A streptogramins, analogues that overcome the resistance conferred by Vat enzymes have not been previously developed 2 . Here we report the design, synthesis, and antibacterial evaluation of group A streptogramin antibiotics with extensive structural variability. Using cryo-electron microscopy and forcefield-based refinement, we characterize the binding of eight analogues to the bacterial ribosome

  天然产物可作为临床使用的大多数抗生素的化学蓝图。这些分子产生的进化过程本质上伴随着抗性机制的共同进化，这些机制会缩短任何给定类别的抗生素 1 的临床寿命。维吉尼亚霉素乙酰转移酶 (Vat) 酶是抗性蛋白，可提供抗链菌素 2 的保护作用，这是一种针对革兰氏阳性菌的强效抗生素，可抑制细菌核糖体 3 。由于选择性地修饰 A 组链菌素的化学复杂的 23 元大环支架的挑战，克服 Vat 酶赋予的抗性的类似物以前尚未开发 2。在这里，我们报告设计，合成，和具有广泛结构变异性的 A 组链霉素抗生素的抗菌评价。使用低温电子显微镜和基于力场的细化，我们以高分辨率表征了八种类似物与细菌核糖体的结合，揭示了延伸到肽基 tRNA 结合位点和占据新生肽出口通道的协同粘合剂的结合相互作用。其中一种类似物对几种金黄色葡萄球菌抗链阳菌素菌株具有优异的活性，在体外表现出降低的乙酰化率，并且在降低感染小鼠模型中的细菌负荷方面
• Novel 1-(mono-o-substituted benzoyl)-3-(substituted pyrazinyl) ureas
  申请人：Eli Lilly and Company

  公开号：US04293552A1

  公开（公告）日：1981-10-06

  Novel 1-(mono-o-substituted benzoyl)-3-(substituted pyrazinyl) ureas, active as insecticides, and methods for their use as insecticides.

  1-(单取代苯甲酰基)-3-(取代吡嗪基)脲类化合物，作为杀虫剂活性，并提供了其作为杀虫剂的使用方法。
• Novel Tetrahydropyrido[1,2-<i>a</i>]isoindolone Derivatives (Valmerins): Potent Cyclin-Dependent Kinase/Glycogen Synthase Kinase 3 Inhibitors with Antiproliferative Activities and Antitumor Effects in Human Tumor Xenografts
  作者：Rajâa Boulahjar、Aziz Ouach、Chiurato Matteo、Stephane Bourg、Myriam Ravache、Rémy le Guével、Séverine Marionneau、Thibauld Oullier、Olivier Lozach、Laurent Meijer、Christiane Guguen-Guillouzo、Saïd Lazar、Mohamed Akssira、Yves Troin、Gérald Guillaumet、Sylvain Routier

  DOI：10.1021/jm3008536

  日期：2012.11.26

  The development of CDK and GSK3 inhibitors has been regarded as a potential therapeutic approach, and a substantial number-of-diverse structures have been reported to inhibit CDKs and GSK-3 beta. in recent years. Only a few molecules have gone through or are currently undergoing clinical trials as CDK and GSK inhibitors. In this paper, we prepared valmerins, a new family containing the tetrahydropyrido[1,2-a]isoindone core. The fused heterocycle was prepared with a straightforward synthesis that was functionalized by a (het)arylurea. Twelve valmerins inhibited the CDK5 and GSK3 with an IC50 < 100 nM. A semiquantitative kinase scoring was realized, and a cellular screening was done. At the end of study, we investigated the in vivo potency of one valmerin. Mice exhibited good tolerance to our lead, which proved its efficacy and clearly blocked tumor growth. Valmerins appear also as good candidates: for further development as anticancer agents.
• Advances in tetrahydropyrido[1,2- a ]isoindolone (valmerins) series: Potent glycogen synthase kinase 3 and cyclin dependent kinase 5 inhibitors
  作者：Rajâa Boulahjar、Aziz Ouach、Stéphane Bourg、Pascal Bonnet、Olivier Lozach、Laurent Meijer、Christiane Guguen-Guillouzo、Rémy Le Guevel、Saïd Lazar、Mohamed Akssira、Yves Troin、Gérald Guillaumet、Sylvain Routier

  DOI：10.1016/j.ejmech.2015.06.046

  日期：2015.8

  An efficient synthetic strategy was developed to modulate the structure of the tetrahydropyridine iso-indolone (Valmerin) skeleton. A library of more than 30 novel final structures was generated. Biological activities on CDK5 and GSM as well as cellular effects on cancer cell lines were measured for each novel compound. Additionally docking studies were performed to support medicinal chemistry efforts. A strong GSK3/CDK5 dual inhibitor (38, IC50 GSK3/CDK5 32/84 nM) was obtained. A set of highly selective GSK3 inhibitors was synthesized by fine-tuning structural modifications (29 IC50 GSK3/CDK5 32/320 nM). Antiproliferative effects on cells were correlated with the in vitro Kinase activities and the best effects were obtained with lung and colon cell lines. (C) 2015 Elsevier Masson SAS. All rights reserved.