N-(2,4-dioxo-1,4-dihydro-2H-benzo[d][1,3]oxazin-6-yl)acetamide | 353759-49-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并恶嗪类
• 英文名称: N-(2,4-dioxo-1,4-dihydro-2H-benzo[d][1,3]oxazin-6-yl)acetamide
• 英文别名: 5-Acetamido-isatoic anhydride；N-(2,4-dioxo-1H-3,1-benzoxazin-6-yl)acetamide
• CAS: 353759-49-6
• 化学式: C₁₀H₈N₂O₄
• 分子量: 220.185
• InChiKey: SRKSHSGBBYNHLV-UHFFFAOYSA-N

物化性质

• 密度：
  1.473±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.2
• 重原子数：
  16
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  84.5
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-(2,4-dioxo-1,4-dihydro-2H-benzo[d][1,3]oxazin-6-yl)acetamide 在 potassium fluoride 、 四丁基溴化铵 、 溶剂黄146 、 sodium hydroxide 作用下， 以 乙醇 、 水 、 乙腈 为溶剂， 反应 14.33h， 生成 氟喹酮
  参考文献：
  名称：

  一种氟喹酮的制备方法

  摘要：

  本发明公开了一种氟喹酮的制备方法，该方法以靛红酸酐为起始原料，首先经硝化、还原、乙酰化合成了关键中间体N-（2-氨基-5-乙酰氨基苯甲酰基）邻甲苯胺，再经氨解、环合、氟交换、脱保护得到目标产物氟喹酮；本发明氟喹酮的制备方法，原料廉价易得，降低了生产成本，革除了现有文献方法中高毒高害试剂氟代乙酰氯的使用，具有安全、环保的优点，同时在氟交换反应中使用四丁基溴化铵作为反应的相转移催化剂，大大提高了该步反应的转化率，由起始原料靛红酸酐制备目标产物氟喹酮的总收率可达60.0%以上。

  公开号：

  CN103613549B
• 作为产物：
  描述：

  靛红酸酐 在 硫酸 、 氢气 、 硝酸 作用下， 以 四氢呋喃 为溶剂， 60.0 ℃ 、2.0 MPa 条件下， 反应 5.0h， 生成 N-(2,4-dioxo-1,4-dihydro-2H-benzo[d][1,3]oxazin-6-yl)acetamide
  参考文献：
  名称：

  一种氟喹酮的制备方法

  摘要：

  本发明公开了一种氟喹酮的制备方法，该方法以靛红酸酐为起始原料，首先经硝化、还原、乙酰化合成了关键中间体N-（2-氨基-5-乙酰氨基苯甲酰基）邻甲苯胺，再经氨解、环合、氟交换、脱保护得到目标产物氟喹酮；本发明氟喹酮的制备方法，原料廉价易得，降低了生产成本，革除了现有文献方法中高毒高害试剂氟代乙酰氯的使用，具有安全、环保的优点，同时在氟交换反应中使用四丁基溴化铵作为反应的相转移催化剂，大大提高了该步反应的转化率，由起始原料靛红酸酐制备目标产物氟喹酮的总收率可达60.0%以上。

  公开号：

  CN103613549B

文献信息

• [EN] TREATMENT OF CHAGAS DISEASE<br/>[FR] TRAITEMENT DE LA MALADIE DE CHAGAS
  申请人：UNIV DUNDEE

  公开号：WO2015189595A1

  公开（公告）日：2015-12-17

  The invention provides compounds of the formula: wherein L1 and L2 are independently selected from O and S; R1 is C3-C6straight or branched alkyl, C3-C7cycloalkyl, C5-C7cycloalkenyl, adamantly, phenyl or saturated heterocyclyl, any of which being optionally substituted; R2 is H, methyl or ethyl; R5 is NRxCORy, NRxRy, CH2COCH3, CH2C≡N, or a 5- or 6-membered heteroaryl group which is optionally substituted; X, Y and Z are independently N or CH; Rx is independently H or C1-C4alkyl; Ry is independently H, CrC4alkyl, phenyl or benzyl, either of which is optionally substituted; n is 0-3; salts, hydrates and N-oxides, wherein the optional substituents are further defined in the claims. The compounds have utility in the prophylaxis or treatment of trypanosomal diseases, such as T. cruzi (Chagas disease).

  该发明提供了以下式的化合物：其中L1和L2分别选自O和S；R1为C3-C6直链或支链烷基，C3-C7环烷基，C5-C7环烯基，脱氢胆固醇，苯基或饱和杂环烷基，其中任一可选择地被取代；R2为H，甲基或乙基；R5为NRxCORy，NRxRy，CH2COCH3，CH2C≡N，或者是可选择地被取代的5-或6-成员杂芳基团；X、Y和Z分别为N或CH；Rx分别为H或C1-C4烷基；Ry分别为H，CrC4烷基，苯基或苄基，其中任一可选择地被取代；n为0-3；盐、水合物和N-氧化物，其中可选择的取代基在权利要求中进一步定义。这些化合物在预防或治疗锥虫病等锥虫病方面具有用途。
• Bis-Halogen-Anthraniloyl-Substituted Nucleoside 5′-Triphosphates as Potent and Selective Inhibitors of<i>Bordetella pertussis</i>Adenylyl Cyclase Toxin
  作者：Jens Geduhn、Stefan Dove、Yuequan Shen、Wei-Jen Tang、Burkhard König、Roland Seifert

  DOI：10.1124/jpet.110.174219

  日期：2011.1

  Whooping cough is caused by Bordetella pertussis and still constitutes one of the top five causes of death in young children, particularly in developing countries. The calmodulin-activated adenylyl cyclase (AC) toxin CyaA substantially contributes to disease development. Thus, potent and selective CyaA inhibitors would be valuable drugs for the treatment of whooping cough. However, it has been difficult to obtain potent CyaA inhibitors with selectivity relative to mammalian ACs. Selectivity is important for reducing potential toxic effects. In a previous study we serendipitously found that bis-methylanthraniloyl (bis-MANT)-IMP is a more potent CyaA inhibitor than MANT-IMP ( Mol Pharmacol 72: 526–535, 2007). These data prompted us to study the effects of a series of 32 bulky mono- and bis-anthraniloyl (ANT)-substituted nucleotides on CyaA and mammalian ACs. The novel nucleotides differentially inhibited CyaA and ACs 1, 2, and 5. Bis-ANT nucleotides inhibited CyaA competitively. Most strikingly, bis-Cl-ANT-ATP inhibited CyaA with a potency ≥100-fold higher than ACs 1, 2, and 5. In contrast to MANT-ATP, bis-MANT-ATP exhibited low intrinsic fluorescence, thereby substantially enhancing the signal-to noise ratio for the analysis of nucleotide binding to CyaA. The high sensitivity of the fluorescence assay revealed that bis-MANT-ATP binds to CyaA already in the absence of calmodulin. Molecular modeling showed that the catalytic site of CyaA is sufficiently spacious to accommodate both MANT substituents. Collectively, we have identified the first potent CyaA inhibitor with high selectivity relative to mammalian ACs. The fluorescence properties of bis-ANT nucleotides facilitate development of a high-throughput screening assay.

  百日咳由百日咳杆菌（Bordetella pertussis）引起，目前仍是导致幼儿死亡的五大原因之一，在发展中国家尤其如此。钙调蛋白激活的腺苷酸环化酶（AC）毒素 CyaA 在很大程度上导致了疾病的发生。因此，强效的选择性 CyaA 抑制剂将是治疗百日咳的重要药物。然而，要获得相对于哺乳动物 AC 具有选择性的强效 CyaA 抑制剂一直很困难。选择性对于减少潜在的毒性作用非常重要。在之前的一项研究中，我们偶然发现双甲基蒽酰（bis-MANT）-IMP 是一种比 MANT-IMP 更有效的 CyaA 抑制剂（《分子药理学》72：526-535，2007 年）。这些数据促使我们研究了一系列 32 种笨重的单蒽酰和双蒽酰（ANT）取代的核苷酸对 CyaA 和哺乳动物 AC 的影响。新型核苷酸对 CyaA 和 AC 1、2 和 5 有不同的抑制作用。双-ANT 核苷酸对 CyaA 有竞争性抑制作用。最引人注目的是，双Cl-ANT-ATP对CyaA的抑制作用比AC 1、2和5高出≥100倍。与 MANT-ATP 相反，双-MANT-ATP 显示出较低的本征荧光，从而大大提高了分析核苷酸与 CyaA 结合的信噪比。荧光检测的高灵敏度表明，在没有钙调蛋白的情况下，双-MANT-ATP 也能与 CyaA 结合。分子建模显示，CyaA 的催化位点足够宽敞，可以容纳两个 MANT 取代基。总之，我们发现了第一个对哺乳动物 AC 具有高选择性的强效 CyaA 抑制剂。双-ANT 核苷酸的荧光特性促进了高通量筛选试验的开发。
• Functionalization Processes and Reactants Used in Such Processes Using an Isatoic Anhydride or a Derivative Thereof, Biological Molecules Thus Treated and Kits
  申请人：Burr Arnaud

  公开号：US20130253179A1

  公开（公告）日：2013-09-26

  The present invention relates to a process of functionalising at least one ribonucleic acid (RNA) molecule which comprises the following steps: a) having at least: a binding molecule constituted by an isatoic anhydride or a derivative thereof, a group of interest, and a binding arm linking the binding molecule with the group of interest, b) reacting the anhydride function of the binding molecule with at least one hydroxyl group in: position 2′ of the ribose of one of the RNA nucleotides, and/or position(s) 2′ and/or 3′ of the ribose of the nucleotide at the 3′ terminal end of the RNA, and c) obtaining an anthranilate linking, via the binding arm, the RNA to the group of interest. The invention also relates to a functionalising reagent able to be used in such processes, a functionalised biological RNA molecule capable of being obtained by these processes and a kit for detecting a target RNA molecule comprising such a reagent. Said invention finds a preferential application in the field of in vitro diagnosis.

  本发明涉及一种功能化至少一个核糖核酸(RNA)分子的过程，包括以下步骤：a)至少具有：由异吲哚酸酐或其衍生物组成的结合分子，一个感兴趣的基团和将结合分子与感兴趣基团连接的结合臂；b)反应结合分子的酸酐官能团与RNA核苷酸中至少一个羟基反应，其中该核苷酸的核糖在2'位，和/或RNA 3'末端核苷酸的核糖在2'和/或3'位；c)通过结合臂获得一种蒽酰胺连接，将RNA与感兴趣基团连接。本发明还涉及一种可用于此类过程的功能化试剂、能够通过这些过程获得的功能化生物RNA分子以及用于检测靶RNA分子的试剂盒。本发明在体外诊断领域中具有优选应用。
• Discovery and Optimization of a Compound Series Active against <i>Trypanosoma cruzi</i>, the Causative Agent of Chagas Disease
  作者：Justin R. Harrison、Sandipan Sarkar、Shahienaz Hampton、Jennifer Riley、Laste Stojanovski、Christer Sahlberg、Pia Appelqvist、Jessey Erath、Vinodhini Mathan、Ana Rodriguez、Marcel Kaiser、Dolores Gonzalez Pacanowska、Kevin D. Read、Nils Gunnar Johansson、Ian H. Gilbert

  DOI：10.1021/acs.jmedchem.9b01852

  日期：2020.3.26

  Chagas disease is caused by the protozoan parasite Trypanosoma cruzi. It is endemic in South and Central America and recently has been found in other parts of the world, due to migration of chronically infected patients. The current treatment for Chagas disease is not satisfactory, and there is a need for new treatments. In this work, we describe the optimization of a hit compound resulting from the phenotypic screen of a library of compounds against T. cruzi. The compound series was optimized to the level where it had satisfactory pharmacokinetics to allow an efficacy study in a mouse model of Chagas disease. We were able to demonstrate efficacy in this model, although further work is required to improve the potency and selectivity of this series.
• EP1505067
  申请人：——

  公开号：——

  公开（公告）日：——