4-(4-hydroxybutoxy)-3-(phenylsulfonyl)-1,2,5-oxadiazole 2-oxide | 452095-47-5

• 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-hydroxybutoxy)-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}butan-1-ol；4-[[4-(benzenesulfonyl)-5-oxido-1,2,5-oxadiazol-5-ium-3-yl]oxy]butan-1-ol
• CAS: 452095-47-5
• 化学式: C₁₂H₁₄N₂O₆S
• 分子量: 314.319
• InChiKey: BHVOYWSKJSRXRV-UHFFFAOYSA-N

物化性质

• 沸点：
  574.8±60.0 °C(Predicted)
• 密度：
  1.48±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  21
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 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-hydroxybutoxy)-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]butyl 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-hydroxybutoxy)-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

• Synthesis and Biological Evaluation of Novel Furozan-Based Nitric Oxide-Releasing Derivatives of Oridonin as Potential Anti-Tumor Agents
  作者：Dahong Li、Lei Wang、Hao Cai、Yihua Zhang、Jinyi Xu

  DOI：10.3390/molecules17067556

  日期：——

  To search for novel nitric oxide (NO) releasing anti-tumor agents, a series of novel furoxan/oridonin hybrids were designed and synthesized. Firstly, the nitrate/nitrite levels in the cell lysates were tested by a Griess assay and the results showed that these furoxan-based NO-releasing derivatives could produce high levels of NO in vitro. Then the anti-proliferative activity of these hybrids against four human cancer cell lines was also determined, among which, 9h exhibited the most potential anti-tumor activity with IC50 values of 1.82 µM against K562, 1.81 µM against MGC-803 and 0.86 µM against Bel-7402, respectively. Preliminary structure-activity relationship was concluded based on the experimental data obtained. These results suggested that NO-donor/natural product hybrids may provide a promising approach for the discovery of novel anti-tumor agents.

  为寻找新型一氧化氮（NO）释放抗肿瘤剂，设计并合成了一系列新型呋咱/冬凌草甲素杂化物。首先，通过Griess试剂盒检测细胞裂解液中的硝酸盐/亚硝酸盐水平，结果显示这些基于呋咱的NO释放衍生物在体外能产生高水平的NO。随后测定了这些杂化物对四种人类癌细胞系的抗增殖活性，其中9h表现出了最大的抗癌潜力，对K562、MGC-803和Bel-7402的IC50值分别为1.82 µM、1.81 µM和0.86 µM。根据所得实验数据，得出了初步的构效关系结论。这些结果表明，NO供体/天然产物杂化物可能是发现新型抗肿瘤药物的有前景途径。
• 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。
• NO供体型苦参碱衍生物、其制备方法及医药 用途
  申请人：何黎琴

  公开号：CN103694238B

  公开（公告）日：2017-02-08

  本发明涉及药物化学和药物治疗学领域，具体涉及NO供体型苦参碱衍生物及其制备方法和在制药中的应用。该类化合物具有抗肿瘤作用，可用于制备抗肿瘤药物。本发明还涉及这类化合物的制备方法。
• Design and synthesis of novel senkyunolide analogues as neuroprotective agents
  作者：Yuanying Fang、Rikang Wang、Qi Wang、Yongbing Sun、Saisai Xie、Zunhua Yang、Min Li、Yi Jin、Shilin Yang

  DOI：10.1016/j.bmcl.2018.01.018

  日期：2018.2

  A class of senkyunolide analogues bearing benzofuranone fragment were designed, synthesized and evaluated for their neuroprotective effect in models of oxygen glucose deprivation (OGD) and oxidative stress. All tested compounds showed neuroprotection profile based on the cell viability assay. In particular, derivatives 1f–1i possessing furoxan-based nitric oxide releasing functionality exhibited significant

  设计，合成并评估了一类带有苯并呋喃酮片段的senkyunolide类似物在氧葡萄糖剥夺（OGD）和氧化应激模型中的神经保护作用。基于细胞活力测定法，所有测试的化合物均显示出神经保护作用。特别是，具有基于呋喃喃的一氧化氮释放功能的衍生物1f – 1i在OGD模型中表现出显着的生物学活性。更重要的是，含有短接头与呋喃喃的化合物1g在浓度为100μM时显示出最有效的神经保护作用（细胞存活率高达145.2％）。此外，1g在氧化应激模型中也表现出中等水平的神经保护作用。
• 呋咱氮氧类NO供体型他汀衍生物及其制备方 法
  申请人：中国医药集团总公司四川抗菌素工业研究所

  公开号：CN110128368B

  公开（公告）日：2020-07-10

  本发明公开了一种呋咱氮氧类NO供体型他汀衍生物及其制备方法，属于药物化学合成技术领域，其具有如下通式所示的结构式：其中，所示R为烷烃基，R1为他汀残基，R2为芳基或芳磺酰基；本发明选择了他汀药物与NO供体“杂交”，NO和他汀药物均对动脉粥样硬化有良好的治疗作用，有效地避免了二者作用机制不匹配的问题；另外，本发明选择了4‑香豆酸作为连接基，可以有效地增强药物的疗效；本发明的化合物在体外均可有效释放NO，为NO供体抗动脉粥样硬化药物的开发做出了有益的尝试。