N-[4-(N'-羟基甲脒基)苯基]乙酰胺 | 6577-60-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: N-[4-(N'-羟基甲脒基)苯基]乙酰胺
• 英文名称: N-(4-(N'-hydroxycarbamimidoyl)phenyl)acetamide
• 英文别名: N-[4-[(Z)-N'-hydroxycarbamimidoyl]phenyl]acetamide
• CAS: 6577-60-2
• 化学式: C₉H₁₁N₃O₂
• mdl: MFCD01312291
• 分子量: 193.205
• InChiKey: OSOXQDDYEWGWLY-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：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  87.7
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N-[4-(N'-羟基甲脒基)苯基]乙酰胺 在 三乙胺 、 sodium hydroxide 作用下， 以 1,3-二噁烷 、 二氯甲烷 、 甲苯 为溶剂， 反应 216.75h， 生成 4-(3-(4-acetamidophenyl)-1,2,4-oxadiazol-5-yl)benzoic acid
  参考文献：
  名称：

  Design and synthesis of 3,5-substituted 1,2,4-oxadiazoles as catalytic inhibitors of human DNA topoisomerase IIα

  摘要：

  Cancer constitutes a group of diseases linked to abnormal cell growth that can potentially spread to other parts of the body and is one of the most common causes of death. The molecular motors - DNA topoisomerases - that enable topological changes of the DNA molecule are one of the most established targets of cancer therapies. Due to known limitations of established topo II poisons such as cardiotoxicity, induction of secondary malignancies and recognized cancer cell resistance, an emerging group of catalytic topo II inhibitors attempts to circumvent these challenges. Currently, this approach comprises several subgroups of mechanistically diverse inhibitors, one of which are compounds that act by binding to their ATPase domain.In this study we have designed, synthesized and characterized a new series of 3,5-substituted 1,2,4-oxadiazoles that act as catalytic inhibitors of human topo II alpha. The introduction of the substituted rigid substitutions on the oxadiazole backbone was intended to enhance the interactions with the ATP binding site. In the inhibition assays selected compounds revealed a new class of catalytic inhibitors targeting this molecular motor and showed binding to the isolated topo II alpha ATPase domain. The predicted inhibitor binding geometries were evaluated in molecular dynamics simulations and subsequently dynophore models were derived, which provided a deeper insight into molecular recognition with its macromolecular target. Selected compounds also displayed in vitro cytotoxicity on the investigated MCF-7 cancer cell line and did not induce double-strand breaks (DSB), thus displaying a mechanism of action diverse from the topo II poisons also on the cellular level. The substituted oxadiazoles thus comprise a chemical class of interesting compounds that are synthetically fully amenable for further optimization to anticancer drugs.

  DOI：

  10.1016/j.bioorg.2020.103828
• 作为产物：
  描述：

  4-乙酰氨苯甲腈 在 盐酸羟胺 、 碳酸氢钠 作用下， 以 乙醇 为溶剂， 反应 6.0h， 以91%的产率得到N-[4-(N'-羟基甲脒基)苯基]乙酰胺
  参考文献：
  名称：

  室温合成带有1,2,4-恶二唑基团的药学上重要的羧酸

  摘要：

  已经开发了一种有效且温和的一锅操作规程，用于通过a胺肟与二羧酸酐在NaOH / DMSO介质中的反应来合成1,2,4-恶二唑。该方法可以合成具有1,2,4-恶二唑基序的不同取代的羧酸，该基团是药物研究的常用组成部分，产率中等至优异。反应范围包括芳族和杂芳族酰胺肟以及五元，六元和七元酸酐。该方法的优点是证明了克级可缩放性和使用廉价的起始原料，从工艺化学的角度来看，这对于将来的工业应用至关重要。

  DOI：

  10.1016/j.tetlet.2017.08.020

文献信息

• Structure–Reactivity Relationships on Substrates and Inhibitors of the Lysine Deacylase Sirtuin 2 from <i>Schistosoma mansoni</i> (<i>Sm</i>Sirt2)
  作者：Daria Monaldi、Dante Rotili、Julien Lancelot、Martin Marek、Nathalie Wössner、Alessia Lucidi、Daniela Tomaselli、Elizabeth Ramos-Morales、Christophe Romier、Raymond J. Pierce、Antonello Mai、Manfred Jung

  DOI：10.1021/acs.jmedchem.9b00638

  日期：2019.10.10

  vitro screening of the GSK Kinetobox library and structure–activity relationships of identified hits led to the first SmSirt2 inhibitors with activity in the low micromolar range. Several SmSirt2 inhibitors showed potency against both larval schistosomes (viability) and adult worms (pairing, egg laying) in culture without general toxicity to human cancer cells.

  目前可用于治疗被忽视的血吸虫病的唯一药物是吡喹酮，耐药性的出现使得对新型治疗剂的研究变得必要和紧迫。为此，靶向曼氏血吸虫表观遗传酶（其调节寄生虫的生命周期）作为一种有前途的方法应运而生。由于人类sirtuin抑制剂对寄生虫存活和繁殖的强烈影响，血吸虫sirtuins被认为是潜在的治疗靶标。曼氏沙门氏菌sirtuin 2（Sm Sirt2）的合成底物的体外测试和肉豆蔻酰化肽的动力学实验证明赖氨酸长链脱酰作用是固有的SmSirt2活性除其首次已知的脱乙酰基酶活性外。对GSK Kinetobox文库进行集中的体外筛选以及已确定的基因敲击物的构效关系，导致了首批具有低微摩尔范围活性的Sm Sirt2抑制剂。几种Sm Sirt2抑制剂在培养中显示出对幼虫血吸虫（存活力）和成虫（配对，产卵）的效力，而对人癌细胞没有一般毒性。
• [EN] MORPHOLINONE COMPOUNDS AS FACTOR IXA INHIBITORS<br/>[FR] COMPOSÉS DE MORPHOLINONE EN TANT QU'INHIBITEURS DE FACTEUR IXA
  申请人：MOCHIDA PHARM CO LTD

  公开号：WO2010065717A1

  公开（公告）日：2010-06-10

  The present invention provides a compound of Formula (I) as described herein, or a pharmaceutically acceptable salt or a solvate thereof. The present invention also provides pharmaceutical compositions comprising one or more said compounds, and methods for using said compounds for treating or preventing a thromboses, embolisms, hypercoagulability or fibrotic changes.

  本发明提供了如下描述的化合物I的化合物，或其药用可接受的盐或溶剂。本发明还提供包含一个或多个所述化合物的药物组合物，以及使用所述化合物治疗或预防血栓、栓塞、高凝血性或纤维变化的方法。
• Copper‐Catalyzed Selective N‐Arylation of Oxadiazolones by Diaryliodonium Salts
  作者：Natalia S. Soldatova、Artem V. Semenov、Kirill K. Geyl、Sergey V. Baykov、Anton A. Shetnev、Anna S. Konstantinova、Mikhail M. Korsakov、Mekhman S. Yusubov、Pavel S. Postnikov

  DOI：10.1002/adsc.202100426

  日期：2021.7.20

  Here, we report the method for copper-catalyzed N-arylation of diverse oxadiazolones by diaryliodonium salts under mild conditions in high yields (up to 92%) using available CuI as a catalyst. The developed method allows utilizing both symmetric and unsymmetric diaryliodonium salts bearing auxiliary groups such as 2,4,6-trimethoxyphenyl (TMP). We found that the steric effects in aryl moieties determined

  在这里，我们报告了使用可用的 CuI 作为催化剂在温和条件下以高产率（高达 92%）通过二芳基碘盐对不同恶二唑酮进行铜催化 N-芳基化的方法。所开发的方法允许使用带有辅助基团（例如 2,4,6-三甲氧基苯基 (TMP)）的对称和不对称二芳基碘盐。我们发现芳基部分的空间效应决定了 1,2,4-oxadiazol-5(4 H )-ones的 N-和 O-芳基化的化学选择性。甲基取代的二芳基碘盐显示出作为选择性芳基化试剂的巨大潜力。结构研究表明 1,2,4-oxadiazol-5(4 H)-对空间位阻二芳基碘鎓盐的芳基化的影响。还证明了所提出方法的合成应用对 1,3,4-恶二唑-2(3 H )-酮和 1,2,4-恶二唑-5-硫醇的选择性芳基化。
• A cascade process for directly converting nitriles (RCN) to cyanamides (RNHCN) <i>via</i> SO₂F₂-activated Tiemann rearrangement
  作者：Guofu Zhang、Yiyong Zhao、Chengrong Ding

  DOI：10.1039/c9ob01547g

  日期：——

  practical process for the direct conversion of nitriles to cyanamides was newly discovered and exhibited a wide substrate scope as well as great functional group-tolerability (36 examples). In this efficient strategy, the in situ generated amidoximes obtained from the reaction of nitriles with hydroxylamine subsequently underwent Tiemann rearrangement, producing the corresponding cyanamides with great

  最近发现了一种简单，温和且实用的腈直接转化为氰胺的方法，该方法具有广泛的底物范围和强大的官能团耐受性（36个实例）。在这种有效的策略中，从腈与羟胺的反应中获得的原位生成的氨基肟，随后进行了Tiemann重排，在SO2F2下以高分离产率生产了相应的氰酰胺。另外，据报道，对照实验阐明了参与形成和消除关键中间体磺酰酯的初步机制。
• Preparation of Amidines by Amidoxime Reduction with Potassium Formate
  作者：Marija Sollner Dolenc、Kristina Nadrah

  DOI：10.1055/s-2007-977444

  日期：——

  Amidines can be prepared by reducing acylated amid-oxime with potassium formate. The method has proved to be very simple and effective.

  脒可以通过用甲酸钾还原酰化酰胺肟来制备。该方法已被证明是非常简单和有效的。