4-((4-hydroxybut-2-yn-1-yl)oxy)-3-(phenylsulfonyl)-1,2,5-oxadiazole 2-oxide | 452095-56-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 4-((4-hydroxybut-2-yn-1-yl)oxy)-3-(phenylsulfonyl)-1,2,5-oxadiazole 2-oxide
• 英文别名: 4-{[4-(Benzenesulfonyl)-5-oxo-1,2,5lambda~5~-oxadiazol-3-yl]oxy}but-2-yn-1-ol；4-[[4-(benzenesulfonyl)-5-oxido-1,2,5-oxadiazol-5-ium-3-yl]oxy]but-2-yn-1-ol
• CAS: 452095-56-6
• 化学式: C₁₂H₁₀N₂O₆S
• 分子量: 310.287
• InChiKey: AJJJIWYQURFNED-UHFFFAOYSA-N

物化性质

• 沸点：
  612.1±65.0 °C(Predicted)
• 密度：
  1.46±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  124
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  4-((4-hydroxybut-2-yn-1-yl)oxy)-3-(phenylsulfonyl)-1,2,5-oxadiazole 2-oxide 在 4-二甲氨基吡啶 、 N,N'-二环己基碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 反应 4.0h， 生成 4-[[4-(benzenesulfonyl)-5-oxido-1,2,5-oxadiazol-5-ium-3-yl]oxy]but-2-ynyl 4-[6,7-dimethoxy-1-(phenoxymethyl)-3,4-dihydro-1H-isoquinolin-2-yl]-4-oxobutanoate
  参考文献：
  名称：

  Synthesis and evaluation of furoxan-based nitric oxide-releasing derivatives of tetrahydroisoquinoline as anticancer and multidrug resistance reversal agents

  摘要：

  Multidrug resistance in tumor cells poses a major obstacle to efficient chemotherapy. Several types of agents have been recognized as multidrug resistance inhibitors, among which the tetrahydroisoquinolines is the most studied. In current study 16 furoxan-based nitric oxide-releasing derivatives of tetrahydroisoquinoline were synthesized. Their cytotoxic activities and effects in reversing multidrug resistance have been evaluated. The results revealed that these compounds had moderate cytotoxic effects. Compounds 7a-f, 7h, and 7l showed higher cytotoxicities than the rest, but lower than adriamycin on K562 cell line. Compounds 7d, 7f, and 7l exhibited potent MDR reversal activities on K562/A02 cell line. The accumulation assay indicated that compounds 7d, 7f, and 7l significantly increased the intracellular accumulation of rhodamine123 in K562/A02 cells. Furthermore, these three compounds produced high concentrations of NO in K562/A02 cells. Potentially, the high concentrations of NO produced by NO donor moieties will lead to an increased cytotoxicity to K562/A02 cells. Our results suggested that compounds 7d, 7f, and 7l had anticancer effects, as well as multidrug resistance reversal effects. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.07.077
• 作为产物：
  描述：

  苯硫基乙酸 在 双氧水 、 溶剂黄146 、 sodium hydroxide 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 8.0h， 生成 4-((4-hydroxybut-2-yn-1-yl)oxy)-3-(phenylsulfonyl)-1,2,5-oxadiazole 2-oxide
  参考文献：
  名称：

  Aurover tin B衍生物及其制备方法与应用

  摘要：

  本发明提供了一种aurovertin B衍生物和aurovertin B衍生物的制备方法，以及aurovertin B衍生物在制备治疗三阴乳腺癌的药物中的应用。本发明所述的aurovertin B衍生物极性得到明显提高，有利于制剂和体内生物利用度的提高；具有更好的成药性；另外，本发明所述的aurovertin B衍生物与aurovertin B相比，化合物的活性得到了提高，并降低了对正常细胞的毒性，提高其成药性。因此aurovertin B衍生物在制备治疗三阴乳腺癌的药物中有极好的应用前景，特别是三阴乳腺癌细胞为HCC1937细胞和MDA‑MB‑231细胞时药效活性极佳。

  公开号：

  CN112094278B

文献信息

• Discovery of novel antitumor nitric oxide-donating β -elemene hybrids through inhibiting the PI3K/Akt pathway
  作者：Jichao Chen、Tianyu Wang、Shengtao Xu、Pengfei Zhang、Aijun Lin、Liang Wu、Hequan Yao、Weijia Xie、Zheying Zhu、Jinyi Xu

  DOI：10.1016/j.ejmech.2017.04.045

  日期：2017.7

  sensitivity to U87 cells with IC50 values ranging from 173 to 2 nM. Moreover, most compounds produced high levels of NO in vitro, and the antitumor activity of 11a in U87 cells was markedly attenuated by an NO scavenger (hemoglobin or carboxy-PTIO). Further mechanism studies revealed that 11a caused the G2 phase arrest of the cell cycle and induced apoptosis of U87 cells by preventing the activation of the

  设计并合成了一系列新颖的基于呋喃烷的NO供体β-榄香烯杂种，以提高天然β-榄香烯的抗癌功效。生物测定结果表明，与母体化合物β-榄香烯相比，所有目标化合物对三种癌细胞系（SGC-7901，HeLa和U87）均表现出显着改善的抗增殖活性。有趣的是，这些化合物对U87细胞显示出极好的敏感性，IC50值为173至2 nM。而且，大多数化合物在体外产生高水平的NO，并且NO清除剂（血红蛋白或羧基-PTIO）显着减弱U87细胞中11a的抗肿瘤活性。进一步的机理研究表明，11a通过阻止PI3K / Akt通路的激活，导致细胞周期的G2期停滞并诱导U87细胞凋亡。而且，11a显着抑制了H22肝癌异种移植小鼠模型中的肿瘤生长，其肿瘤抑制率（TIR）为64.8％，优于相同剂量60 mg / kg的β-榄香烯（TIR，49.6％）。在一起，这些新颖的NO供体β-榄香烯衍生物的显着生物学特征可能使它们成为有希望的人癌症干预候选者。
• Design, synthesis and apoptosis-related antiproliferative activities of chelidonine derivatives
  作者：Xueyan Huang、Keguang Cheng、Lilin Liu、Xu Hu、Xiang Gao、Haonan Li、Fanxing Xu、Zhanlin Li、Huiming Hua、Dahong Li

  DOI：10.1016/j.bmcl.2019.126913

  日期：2020.2

  To get chelidonine derivatives with enhanced antiproliferative activity and selectivity, a series of nitric oxide donating derivatives (10a-f and 11a-j) were designed, synthesized and biologically evaluated. Compared with chelidonine, these compounds exhibited lower IC50 values against human hepatoma cells HepG2, breast cancer cells MCF-7, colon cancer cells HCT-116, as well as leukemia cells K562

  为了获得具有增强的抗增殖活性和选择性的螯胺碱衍生物，设计，合成了一系列的一氧化氮供体衍生物（10a-f和11a-j）并对其进行了生物学评估。与螯合物相比，这些化合物对人肝癌细胞HepG2，乳腺癌细胞MCF-7，结肠癌细胞HCT-116和白血病细胞K562的IC50值较低。化合物11j对上述四个细胞的抗增殖活性最强，IC50值分别为3.91、6.90、4.36和1.12μM。然而，它显示出对人外周血单个核细胞（PBMC）的IC50值> 40μM，这证明了正常和癌细胞之间的高选择性。在进一步的机制研究中，11j显示了诱导K562细胞凋亡的能力，S期细胞周期停滞和线粒体膜电位障碍。此外，发现11j可有效促进促凋亡蛋白Bad的表达并抑制抗凋亡蛋白Bcl-xL，过氧化氢酶，survivin，claspin和clusterin的表达。
• Synthesis of lathyrane diterpenoid nitrogen-containing heterocyclic derivatives and evaluation of their anti-inflammatory activities
  作者：Wang Wang、Liangliang Xiong、Yutong Li、Zhuorui Song、Dejuan Sun、Hua Li、Lixia Chen

  DOI：10.1016/j.bmc.2022.116627

  日期：2022.2

  derivatization, three series of lathyrane diterpenoid derivatives were designed and synthesized based combination principles, including pyrazole, thiazole and furoxan moieties. Biological evaluation indicated that compound 23d exhibited excellently inhibitory activity on LPS-induced NO production in RAW264.7 cells (IC50 = 0.38 ± 0.18 μM). The preliminary structure–activity relationships (SARs) suggested

  作为我们正在进行的二萜衍生化工作，基于组合原理设计和合成了三个系列的二萜衍生物，包括吡唑、噻唑和呋喃部分。生物学评估表明，化合物23d对 LPS 诱导的 RAW264.7 细胞中的 NO 产生具有极好的抑制活性（IC 50  = 0.38 ± 0.18 μM）。初步构效关系 (SARs) 表明，苯磺酰基取代的呋喃部分具有最强的提高 lathyrane 二萜类化合物抗炎活性的能力。此外，化合物23d显着降低 ROS 水平。其分子机制与抑制Nrf2/HO-1通路的转录激活有关。基于这些考虑，23d可能是一种很有前途的抗炎剂，值得进一步探索。
• Synthesis and Biological Evaluation of Nitric Oxide-Donating Thalidomide Analogues as Anticancer Agents
  作者：Tao Wang、Yi-Hua Zhang、Xiang-Wen Kong、Yi-Sheng Lai、Hui Ji、Yan-Ping Chen、Si-Xun Peng

  DOI：10.1002/cbdv.200800014

  日期：2009.4

  In search of more potent anticancer agents, 15 nitric oxide (NO)-donating thalidomide analogues, 6a, 6b, 8a-8e, and 13a-13h, were designed and synthesized. Cytotoxicity of these compounds was evaluated in vitro against three human tumor cell lines (HepG2, A549, and PC-3). The results indicated that 13a-13d exhibited notable anticancer activities comparable to or stronger than that of 5-fluorouracil

  为了寻找更有效的抗癌剂，设计并合成了 15 种一氧化氮 (NO) 供体沙利度胺类似物 6a、6b、8a-8e 和 13a-13h。这些化合物对三种人类肿瘤细胞系（HepG2、A549 和 PC-3）的体外细胞毒性进行了评估。结果表明，13a-13d表现出与5-氟尿嘧啶(5-FU)相当或更强的显着抗癌活性。根据获得的实验数据，还讨论了构效关系。通常，目标化合物的细胞毒活性与 NO 供体的类型密切相关，连接到 NO 供体的间隔物的长度对生物活性也很重要。
• Synthesis and Bioactivity of Furoxan-Based Nitric Oxide-Releasing Colchicine Derivatives as Anticancer Agents
  作者：Li Hong Shen、Sheng Li Wang、Hong Yu Li、Yi Sheng Lai、Li Jie Liu

  DOI：10.14233/ajchem.2013.13635

  日期：——

  A series of novel nitric oxide-donating colchicine derivatives (9a-j) were synthesized by coupling furoxan with N-methyl colchiceinamide through an appropriate spacer arm and their cytotoxicity against four human cancer cell lines in vitro were evaluated by MTT method. It was found that many of the derivatives displayed significant activity, particularly, compound 9f showed more potent cytotoxic activities than colchicine.

  通过将呋喃并[1,2-a]唑酮与N-甲基秋水仙酰胺通过适当的间隔臂偶联，合成了一系列新的NO供体型秋水仙碱衍生物（9a-j），并采用MTT法评估了它们对四种人癌细胞系的体外细胞毒性。结果发现，许多衍生物表现出显著的活性，特别是化合物9f的细胞毒性活性显著强于秋水仙碱。