5-羟甲基-呋喃-2-甲醛肟 | 5985-31-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 杂芳族化合物
• 中文名称: 5-羟甲基-呋喃-2-甲醛肟
• 英文名称: (E)-5-(hydroxymethyl)furan-2-carbaldehyde oxime
• 英文别名: 5-hydroxymethyl-furan-2-carbaldehyde oxime；5-oxymethyl-furfur-syn-aldoxime；5-Hydroxymethyl-furan-2-carbaldehyd-oxim；5-Oxymethyl-furfur-syn-aldoxim；[5-[(E)-hydroxyiminomethyl]furan-2-yl]methanol
• CAS: 5985-31-9
• 化学式: C₆H₇NO₃
• 分子量: 141.126
• InChiKey: BTBUWOXPYDGVSW-XVNBXDOJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.2
• 重原子数：
  10
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  66
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  5-羟甲基-呋喃-2-甲醛肟 生成 (Z)-5-(hydroxymethyl)furan-2-carbaldehyde oxime
  参考文献：
  名称：

  Kiermayer, Chemiker-Zeitung, Chemische Apparatur, 1895, vol. 19, p. 1004

  摘要：

  DOI：
• 作为产物：
  描述：

  果糖 在 盐酸羟胺 、 水 、 sodium carbonate 作用下， 生成 5-羟甲基-呋喃-2-甲醛肟
  参考文献：
  名称：

  Kiermayer, Chemiker-Zeitung, Chemische Apparatur, 1895, vol. 19, p. 1004

  摘要：

  DOI：

文献信息

• Metabolically stable 5-HMF derivatives for the treatment of hypoxia
  申请人：King Abdulaziz University

  公开号：US10836729B1

  公开（公告）日：2020-11-17

  5-HMF derivative compounds that bind covalently with hemoglobin are provided. Methods of treating sickle cell disease and other hypoxia-related disorders by administering such compounds are also provided.

  提供了与血红蛋白共价结合的5-HMF衍生物化合物。还提供了通过给予这些化合物来治疗镰状细胞病和其他缺氧相关疾病的方法。
• Targeted modification of furan‐2‐carboxaldehydes into Michael acceptor analogs yielded <scp>long‐acting</scp> hemoglobin modulators with dual antisickling activities
  作者：Abdelsattar M. Omar、Osheiza Abdulmalik、Khalid M. El‐Say、Mohini S. Ghatge、Mojisola Cyril‐Olutayo、Steven Paredes、Mohammed Al‐Awadh、Moustafa E. El‐Araby、Martin K. Safo

  DOI：10.1111/cbdd.14371

  日期：2024.1

  Sickle cell disease (SCD) is the most common genetic disorder, affecting millions of people worldwide. Aromatic aldehydes, which increase the oxygen affinity of human hemoglobin to prevent polymerization of sickle hemoglobin and inhibit red blood cell (RBC) sickling, have been the subject of keen interest for the development of effective treatment against SCD. However, the aldehyde functional group metabolic instability has severly hampered their development, except for voxelotor, which was approved in 2019 for SCD treatment. To improve the metabolic stability of aromatic aldehydes, we designed and synthesized novel molecules by incorporating Michael acceptor reactive centers into the previously clinically studied aromatic aldehyde, 5‐hydroxymethylfurfural (5‐HMF). Eight such derivatives, referred to as MMA compounds were synthesized and studied for their functional and biological activities. Unlike 5‐HMF, which forms Schiff‐base interaction with αVal1 nitrogen of hemoglobin, the MMA compounds covalently interacted with βCys93, as evidenced by reverse‐phase HPLC and disulfide exchange reaction, explaining their RBC sickling inhibitory activities, which at 2 mM and 5 mM, range from 0% to 21% and 9% to 64%, respectively. Additionally, the MMA compounds showed a second mechanism of sickling inhibition (12%–41% and 13%–62% at 2 mM and 5 mM, respectively) by directly destabilizing the sickle hemoglobin polymer. In vitro studies demonstrated sustained pharmacologic activities of the compounds compared to 5‐HMF. These findings hold promise for advancing SCD therapeutics.

  摘要镰状细胞病（SCD）是最常见的遗传疾病，影响着全球数百万人。芳香醛能增加人体血红蛋白的氧亲和力，防止镰状血红蛋白聚合，抑制红细胞（RBC）镰状化，因此，开发有效治疗 SCD 的芳香醛一直备受关注。然而，醛官能团的代谢不稳定性严重阻碍了它们的发展，只有伏洛托（voxelotor）除外，该药已于 2019 年获批用于 SCD 治疗。为了提高芳香醛的代谢稳定性，我们将迈克尔受体反应中心加入到之前临床研究的芳香醛--5-羟甲基糠醛（5-HMF）中，设计并合成了新型分子。我们合成了八种这样的衍生物，称为 MMA 化合物，并对其功能和生物活性进行了研究。与 5-HMF 与血红蛋白的 αVal1 氮形成希夫碱相互作用不同，MMA 化合物与 βCys93 发生共价作用，这一点可通过反相 HPLC 和二硫化物交换反应得到证明，这也是它们具有红细胞镰状细胞抑制活性的原因，在 2 mM 和 5 mM 浓度下，抑制活性分别为 0% 至 21% 和 9% 至 64%。此外，MMA 化合物通过直接破坏镰状血红蛋白聚合物的稳定性，显示出第二种镰状细胞抑制机制（2 mM 和 5 mM 时分别为 12%-41% 和 13%-62%）。体外研究表明，与 5-HMF 相比，这些化合物具有持续的药理活性。这些发现为推进 SCD 治疗带来了希望。
• 一种以5-羟甲基糠醛为原料合成2,5-呋喃二甲胺的方法
  申请人：中科国生（杭州）科技有限公司

  公开号：CN117567403A

  公开（公告）日：2024-02-20

  本发明公开了一种以5‑羟甲基糠醛为原料合成2,5‑呋喃二甲胺的方法，包括：将5‑羟甲基糠醛和有机溶剂混合，得到溶液；加入盐酸羟胺后回流搅拌反应；将所得溶液旋干，除去溶剂得到中间产品；将中间产品中加入碳酸氢钾、2,2,6,6‑四甲基哌啶氧化物和二氯甲烷；向反应体系滴入次氯酸钠，加完后反应；向反应后的体系加入水进行两相分离，所得二氯甲烷相旋干和干燥得到固体；将固体、雷尼镍和甲醇加入反应釜中并通入H2反应；经后处理呋喃二甲胺。本发明采用5‑羟甲基糠醛为原料，三步法，避免了一步氢化中羟基易发生副反应，产生低聚物的过程，副产物较少，且易于除去，纯化方法适用于大规模化工生产。
• Insights on Structure–Passive Permeability Relationship in Pyrrole and Furan-Containing Macrocycles
  作者：Huy M. Ly、Michael Desgagné、Duc Tai Nguyen、Christian Comeau、Ulrike Froehlich、Éric Marsault、Pierre-Luc Boudreault

  DOI：10.1021/acs.jmedchem.3c02162

  日期：2024.3.14

  heterocycle-containing, semipeptidic macrocycles, a library was synthesized. These compounds were created by developing two novel reactions described herein: the reduction of activated oximes by LiBH4 and the aqueous reductive mono-N-alkylation of aldehydes using catalytic SmI2 and stoichiometric Zn. The permeability of the macrocycles was evaluated through a parallel artificial membrane permeability assay (PAMPA),

  大环化合物具有公认的治疗潜力，但其有限的细胞渗透性可能阻碍其作为口服药物的开发。为了更好地理解含杂环的半肽大环化合物的结构-渗透性关系，合成了一个文库。这些化合物是通过开发本文描述的两个新反应而产生的：通过LiBH 4还原活化肟以及使用催化SmI 2和化学计量Zn进行醛的水还原单-N-烷基化。通过平行人工膜渗透性测定（PAMPA）评估大环化合物的渗透性，结果表明结构中掺入呋喃的大环化合物比具有吡咯部分的大环化合物具有更好的被动渗透性。带有 2,5-二取代吡咯（内向）的化合物被证明与分子内氢键有关，从而增强了其渗透性。这项研究强调了半肽中杂环部分的影响，创造了高渗透性的大环化合物，从而展示了药物被动扩散超出五规则化学空间的有希望的途径。
• Structure−Activity Relationships of <i>N</i>-Hydroxyurea 5-Lipoxygenase Inhibitors
  作者：Andrew O. Stewart、Pramila A. Bhatia、Jonathan G. Martin、James B. Summers、Karen E. Rodriques、Michael B. Martin、James H. Holms、Jimmie L. Moore、Richard A. Craig、Teodozyj Kolasa、James D. Ratajczyk、Hormoz Mazdiyasni、Francis A. J. Kerdesky、Shari L. DeNinno、Robert G. Maki、Jennifer B. Bouska、Patrick R. Young、Carmine Lanni、Randy L. Bell、George W. Carter、Clint D. W. Brooks

  DOI：10.1021/jm9700474

  日期：1997.6.1

  The discovery of second generation N-hydroxyurea 5-lipoxygenase inhibitors was accomplished through the development of a broad structure-activity relationship (SAR) study. This study identified requirements for improving potency and also extending duration by limiting metabolism. Potency could be maintained by the incorporation of heterocyclic templates substituted with selected lipophilic substituents. Duration of inhibition after oral administration was optimized by identification of structural features in the proximity of the N-hydroxyurea which correlated to low in vitro glucuronidation rates. Furthermore, the rate of in vitro glucuronidation was shown to be stereoselective for certain analogs. (R)-N-[3-[5-(4-Fluorophenoxy)-2-furyl]-1-methyl-2-propynyl]-N-hy- droxyurea (17c) was identified and selected for clinical development.