4-(oxiran-2-ylmethoxy)-2H-chromen-2-one | 81438-31-5

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 香豆素及其衍生物
• 英文名称: 4-(oxiran-2-ylmethoxy)-2H-chromen-2-one
• 英文别名: 4-(2,3-epoxypropoxy)-2H-chromen-2-one；4-(oxiran-2-ylmethoxy)chromen-2-one
• CAS: 81438-31-5
• 化学式: C₁₂H₁₀O₄
• 分子量: 218.209
• InChiKey: MFPIBEJUTQTCFL-UHFFFAOYSA-N

物化性质

• 熔点：
  162 °C(Solv: ethanol (64-17-5))
• 沸点：
  426.4±40.0 °C(Predicted)
• 密度：
  1.36±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  48.1
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-(oxiran-2-ylmethoxy)-2H-chromen-2-one 在 N,N'-二环己基碳二亚胺 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 3.0h， 生成 (S)-1-ethyl 2-[(S)-1-(2-oxo-2H-chromen-4-yl-oxy)-3-(piperidin-1-yl)propan-2-yl] pyrrolidine-1,2-dicarboxylate
  参考文献：
  名称：

  Resolution, absolute configuration and antifilarial activity of coumarinyl amino alcohols

  摘要：

  The resolution of racemic coumarinyl amino alcohols 5-10 was achieved by using the inexpensive and readily accessible chiral resolving agent N-carbethoxy-L-proline (S)-11. Direct esterification of rac-5-10 with (S)-11 furnished diastereomeric esters, which were easily separated by column chromatography. The obtained diastereomers yielded the desired enantiopure coumarinyl amino alcohols (S)-(+)-5-10 and (R)-(-)-5-10 in good yields with high enantiomeric excess on saponification. The absolute configurations were determined by X-ray crystal analysis and/or by comparison of the specific rotations. Furthermore, in in vitro antifilarial motility inhibition assays, enantiopure coumarins (S)-(+)-9, (R)-(-)-9 and (S)-(+)-10, (R)-(-)-10 were found to be less efficient in affecting the viability of macrofilariae of Brugia malayi than their racemic forms 9 and 10, respectively, indicating the synergistic effect of the enantiomers in evoking antifilarial action. (C) 2017 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetasy.2017.04.005
• 作为产物：
  描述：

  4-羟基香豆素 、 环氧氯丙烷 在 三乙胺 作用下， 以 丙酮 为溶剂， 反应 16.0h， 以73.4%的产率得到4-(oxiran-2-ylmethoxy)-2H-chromen-2-one
  参考文献：
  名称：

  新型香豆素-靛红杂种作为有效的抗利什曼病药物：合成、计算机模拟和体外评估

  摘要：

  利什曼病是每年影响近 0.7 至 130 万人的六种主要热带疾病之一，迄今为止治疗选择有限且毒性高。在此，我们报告了新型香豆素结合靛红腙 ( Spf-1 – Spf-10 ) 作为高效和安全的抗利什曼病药物的合成、计算机和体外评估。最初进行分子对接以破译先导分子与热带利什曼原虫( Leishmania tropica ) 靶蛋白 (利什曼原虫溶血素 gp63) 的活性腔的结合确认。在所有停靠的化合物中，只有Spf-6、Spf-8和Spf-10由于强常规氢键和疏水 π 相互作用的模式，显示出高结合亲和力。分子动力学模拟显示了这种键合的稳定模式和基于结构的确认，时间尺度为 50 ns，朝向顶部化合物 ( Spf-10 ) 和蛋白质。这些分析肯定了系统的高稳定性。发现十分之三的化合物对热带利什曼原虫前鞭毛体和无鞭毛体的抗利什曼原虫活性进行了评估，发现在微摩尔浓度（IC 50范围为 0.1 – 4

  DOI：

  10.1016/j.bioorg.2021.104816

文献信息

• Synthesis of Coumarin Derivatives as Inhibitors of Platelet Aggregation
  作者：Yeh-Long Chen、Tai-Chi Wang、Kuan-Han Lee、Cherng-Chyi Tzeng、Ya-Ling Chang、Che-Ming Teng

  DOI：10.1002/hlca.19960790308

  日期：1996.5.8

  In a search for the inhibitors of platelet aggregation, certain coumarin derivatives were synthesized and evaluated for antiplatelet activity against thrombin(Thr)-, arachidonic acid(AA)-, collagen(Col)-, and platelet-activating-factor(PAF)-induced aggregation in washed rabbit platelets. These compounds were synthesized from 4-hydroxycoumarin (1) or naphthalen-1-ol via alkylation and Reformatsky-type

  在寻找血小板聚集抑制剂时，合成了某些香豆素衍生物并评估了其对凝血酶（Thr）-，花生四烯酸（AA）-，胶原蛋白（Col）-和血小板活化因子（PAF）-的抗血小板活性。在洗涤的兔血小板中诱导聚集。这些化合物是由4-羟基香豆素（1）或萘-1-醇经烷基化和Reformatsky型缩合反应合成的（图1-3）。其中，显示了4-[（（2,3,4,5-四氢-4-亚甲基-5-氧代-2-苯基呋喃-2-基）甲氧基] -2 H -1-苯并吡喃-2-酮（6b）IC 50对AA和PAF诱导的聚集产生有效的抗血小板作用值分别为8.21和103.67m̈M（见表1和2）。通过在内酯环的2-苯基上引入适当的取代基，可以进一步提高6b对PAF诱导的聚集的抗血小板效力。
• Organocatalytic Regioselective Concomitant Thiocyanation and Acylation of Oxiranes Using Aroyl Isothiocyanates
  作者：Anju Modi、Wajid Ali、Bhisma K. Patel

  DOI：10.1021/acs.orglett.6b03430

  日期：2017.2.3

  A regioselective and concomitant transfer of thiocyanate (−SCN) and aroyl/acyl (−COR) groups from aroyl/acyl isothiocyanates onto oxiranes was achieved, giving thiocyanato benzoates in 100% atom economy. In this biomimetic organocatalytic process, one part (−SCN) of aroyl/acyl isothiocyanates acts as the nucleophile whereas the other half (−COR) serves as an electrophilic partner.

  实现了硫氰酸酯（-SCN）和芳酰基/酰基（-COR）基团从芳酰基/酰基异硫氰酸酯到氧杂环丁烷上的区域选择性和伴随转移，从而使硫氰酸根合苯甲酸酯的原子经济性为100％。在这种仿生有机催化过程中，一部分（-SCN）的芳酰基/酰基异硫氰酸酯充当亲核试剂，而另一半（-COR）充当亲电伴侣。
• In vitro anti-Leishmania activity of new isomeric cobalt(II)complexes and in silico insights: Mitochondria impairment and apoptosis-like cell death of the parasite
  作者：Samuel M. Rocha、Adolfo Horn Jr.、Aline R. de M. L. Terra、Lara M. Rezende、Felipe F. Moreira、Renato A. DaMatta、Fernando R. Xavier、Rodrigo Cervo、Roberta Cargnelutti、Sreerag N. Moorkkannur、Graysen Owenby、Rajeev Prabhakar、Sérgio H. Seabra、Christiane Fernandes

  DOI：10.1016/j.jinorgbio.2022.112088

  日期：2023.3

  physico-chemical characterization and in vitro antiproliferative activity against the promastigote form of Leishmania amazonensis of two new cobalt(II) coordination compounds (i.e. [Co(HL1)Cl2]0.4,2H2O (1) and [Co(HL2)(Cl)(CH3OH)](ClO4).2H2O (2)) are reported, where HL1 = 4-3-[bis(pyridin-2-ylmethyl)amino]-2-hydroxypropoxy}-2H-chromen-2-one and HL2 = 7-3-[bis(pyridin-2-ylmethyl)amino]-2-hydroxypropoxy}-2H-chromen-2-one

  两种新型钴(II) 配位化合物 (即[ Co (HL1)Cl 2 ]0.4,2H 2 O (1)和 [Co( HL2)(Cl)(CH 3 OH)](ClO 4 ).2H 2 O (2) ) 被报道，其中 HL1 = 4-3-[双(吡啶-2-基甲基)氨基]-2-羟基丙氧基} -2 H -chromen-2-one 和 HL2 = 7-3-[bis(pyridin-2-ylmethyl)amino]-2-hydroxypropoxy}-2 H -chromen-2-one。对络合物(2)进行了 X 射线衍射研究配合物（1）的结构是通过密度泛函理论（DFT）计算建立的。复合物(1)对 LLC-MK2 没有细胞毒性，但复合物(2)有毒。复合物(1)对亚马逊乳杆菌前鞭毛体的IC 50分别为 4.90（24 小时）、3.50（48 小时）和 3. 80 μmol L -1（72 小时），复合物(2)为
• Design, synthesis and bioactivity evaluation of 4-hydroxycoumarin derivatives as potential anti-inflammatory agents against acute lung injury and colitis
  作者：Xiaobo Li、Xinyi Huang、Yunxi Zhao、Zhiwei Zheng、Mi Guo、Zhicao Chen、Pan Chen、Xiang Li、Jing Liao、Miao Jiang、Won-Jea Cho、Young-Chang Cho、Ruifeng Zeng、Qidong Tang、Guang Liang

  DOI：10.1016/j.ejmech.2024.116487

  日期：2024.6

  reactions in mice, confirming its safety . Additionally, the preliminary pharmacokinetic (PK) parameters of in SD rats were also examined, revealing a bioavailability (F) of 28.72 %. In conclusion, is a potential candidate of drug for the treatment of ALI and colitis.

  急性肺损伤（ALI）和炎症性肠病（IBD）是严重影响人们健康的常见炎症性疾病。在此，设计并合成了一系列4-羟基香豆素（4-HC）衍生物。然后通过 ELISA 测定筛选这些化合物对 LPS 诱导的 J774A.1 细胞白细胞介素 6 (IL-6) 释放的抑制作用，化合物的活性比先导化合物 4-HC 高 3 倍。最活跃的化合物在小鼠细胞 J774A.1 和人细胞 THP-1 上释放 IL-6 的 IC 值分别为 4.57 μM 和 6.51 μM。此外，我们还发现它可以作用于 MAPK 通路。基于计算机虚拟对接的靶点预测结果，进行激酶抑制实验，揭示靶向IRAK1是发挥抗炎活性的关键机制。此外，对葡聚糖硫酸钠（DSS）诱导的结肠炎模型和脂糖（LPS）诱导的ALI小鼠模型发挥了良好的治疗作用。急性毒性实验表明，大剂量未引起小鼠不良反应，证实了其安全性。此外，还检查了 SD 大鼠的初步药代动力学 (PK)
• Synthesis and biological evaluation of 4-oxycoumarin derivatives as a new class of antifilarial agents
  作者：Sweta Misra、Lav Kumar Singh、Priyanka、Jyoti Gupta、Shailja Misra-Bhattacharya、Diksha Katiyar

  DOI：10.1016/j.ejmech.2015.02.043

  日期：2015.4

  A series of 4-oxycoumarin derivatives was synthesized, characterized and evaluated in vitro and in vivo for antifilarial activity against the human lymphatic filarial parasite, Brugia malayi. A majority of the compounds studied showed potent in vitro activity with low IC50 values in the micro molar (mu M) range (0.014-1.73 and 0.0056-0.43) against adult worms and microfilariae, respectively. Compounds 8 and 9 were identified to be the most promising antifilarial candidate molecules exhibiting activity in the nanomolar (nM) range. The IC50 values for compound 8 were 14 nM and 5.6 nM while for compound 9 were 94 nM and 13 nM, respectively, for adult worm and microfilaria. These two compounds also displayed promising adulticidal activity (74.9 +/- 4.8% and 69.4 +/- 2.8%, respectively) in the primary rodent (jird) screen. This study also serves as a starting point for investigating structure-activity relationship with different amino substituents. (C) 2015 Elsevier Masson SAS. All rights reserved.

表征谱图