3-(phenylsulfonyl)-4-(piperidin-4-yloxy)-1,2,5-oxadiazole-2-oxide | 1245575-38-5

• 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: 3-(phenylsulfonyl)-4-(piperidin-4-yloxy)-1,2,5-oxadiazole-2-oxide
• 英文别名: 3-(Benzenesulfonyl)-2-oxido-4-piperidin-4-yloxy-1,2,5-oxadiazol-2-ium
• CAS: 1245575-38-5
• 化学式: C₁₃H₁₅N₃O₅S
• 分子量: 325.345
• InChiKey: YJBRCGGERJJDSM-UHFFFAOYSA-N

物化性质

• 熔点：
  78-81 °C
• 沸点：
  561.6±60.0 °C(Predicted)
• 密度：
  1.57±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  115
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  3-(phenylsulfonyl)-4-(piperidin-4-yloxy)-1,2,5-oxadiazole-2-oxide 在 potassium carbonate 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 、 三甲氧基磷 作用下， 以 N,N-二甲基甲酰胺 、 丙酮 为溶剂， 反应 11.0h， 生成 (4-(((2-((3-((4-(phenylsulfonyl)-1,2,5-oxadiazol-3-yl)oxy)propyl)carbamoyl)quinolin-8-yl)oxy)methyl)phenyl)boronic acid
  参考文献：
  名称：

  Nitric oxide-donating and reactive oxygen species-responsive prochelators based on 8-hydroxyquinoline as anticancer agents

  摘要：

  DOI：

  10.1016/j.ejmech.2021.113153
• 作为产物：
  描述：

  呋咱氮氧化物供体 在 三乙基硅烷 、 三氟乙酸 、 sodium hydroxide 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 5.0h， 生成 3-(phenylsulfonyl)-4-(piperidin-4-yloxy)-1,2,5-oxadiazole-2-oxide
  参考文献：
  名称：

  NO供体类化合物、组合物、制备方法和及其应用

  摘要：

  本发明的目的在于提供NO供体类化合物、组合物、制备方法和及其应用，这些化合物组合物在体外抗癌活性测试中表现了很高的抗癌活性，尤其对乳腺癌细胞MDA‑MB‑231、SUM159、MCF‑7、SKBR‑3和4T1具有抑制活性，并且有些化合物的抑制活性高达1μM，可作为治疗癌症的药物以及癌症辅助治疗的药物使用。

  公开号：

  CN110396086B

文献信息

• Novel nitric oxide-releasing derivatives of pyranocarbazole as antitumor agents: Design, synthesis, biological evaluation, and nitric oxide release studies
  作者：Yingda Zang、Lei Huang、Xinyi Chen、Chuangjun Li、Jie Ma、Xiaoguang Chen、Dongming Zhang、Fangfang Lai

  DOI：10.1016/j.ejmech.2022.114832

  日期：2022.12

  In this study, a series of novel furoxan-based nitric oxide (NO) releasing derivatives of pyranocarbazole alkaloids were designed, synthesized, and biologically evaluated against human cancer cell lines. The derivatives showed considerable antiproliferative activities (IC50 = 0.05–7.55 μM) and most compounds showed higher activity in MDA-MB-231 than H460 and HeLa. Especially, the most active derivative

  在这项研究中，设计、合成了一系列新型基于呋喃喃嗣生物碱的一氧化氮 （NO） 释放衍生物，并针对人类癌细胞系进行了生物学评价。衍生物显示出相当大的抗增殖活性 （IC50 = 0.05–7.55 μM），并且大多数化合物在 MDA-MB-231 中显示出比 H460 和 HeLa 更高的活性。特别是，针对 MDA-MB-231 的最活跃衍生物 7a （IC50 = 0.05 μM） 比先导化合物强约 60 倍，与阳性对照紫杉醇相当，并在 MDA-MB-231 中产生高水平的 NO。此外，7a 可显着抑制 MDA-MB-231 肿瘤在体内的生长，毒性低，且 PI3K/Akt 信号通路。这些结果表明，化合物 7a 可能成为进一步研究的有前途的线索。
• Design, synthesis and biological evaluation of nitric oxide-releasing 5-cyano-6-phenyl-2, 4-disubstituted pyrimidine derivatives
  作者：Lingling Chi、Hao Wang、Fuqiang Yu、Chao Gao、Honglin Dai、Xiaojie Si、Yuze Dong、Hongmin Liu、Qiurong Zhang

  DOI：10.1016/j.bmcl.2023.129389

  日期：2023.8

  In this study, a series of nitric oxide (NO) -releasing 5-cyano-6-phenyl-2, 4-disubstituted pyrimidine derivatives were designed and synthesized. In the in vitro biological evaluation, compound 24l exhibited optimal antiproliferative activity against MGC-803 cells with the IC50 value of 0.95 µM, significantly better than that of the positive control 5-FU. In addition, preliminary mechanistic studies

  本研究设计并合成了一系列释放一氧化氮（NO）的5-氰基-6-苯基-2,4-二取代嘧啶衍生物。体外生物学评价中，化合物24l对MGC-803细胞表现出最佳的抗增殖活性，IC 50值为0.95 μM，明显优于阳性对照5-FU。此外，初步机制研究表明24l抑制集落形成并阻断MGC-803细胞处于G0/G1期。DAPI染色、活性氧和细胞凋亡测定表明24l诱导MGC-803细胞凋亡。特别是，最有效的化合物24l产生最高水平的NO，并且与NO清除剂预孵育后，抗增殖活性显着降低。总之，化合物24l可被认为是潜在的候选抗肿瘤剂。
• Design, synthesis and biological evaluation of novel hybrids of quinazoline derivatives and phenylsulfonylfuroxan as potential anti-tumor agents
  作者：Hao Wang、Lingling Chi、Fuqing Yu、Honglin Dai、Chao Gao、Xiaojie Si、Zhengjie Wang、Limin Liu、Peirong Zhao、Yingnan Zhu、Hongmin Liu、Qiurong Zhang

  DOI：10.1007/s00044-023-03093-z

  日期：2023.8

  Among these compounds, 25q also exhibited the most potent NO releasing ability. Overall, all these studies indicate that the designed quinazoline/phenylsulfonylfuroxan hybrids have significant anti-tumor activities and excellent NO releasing ability and 25q has the potential to act as a valuable lead compound for the development of anti-tumor agents. Graphical Abstract

  在这项研究中，设计、合成了一系列新型喹唑啉/苯磺酰呋喃杂化物，并针对五种人类癌细胞系（H1975、MCF-7、Eca-109、MGC-803 和 A549）进行了生物学评估。大多数杂交体对测试的五种癌细胞表现出相当大的抗增殖活性，而化合物25q对H1975细胞和MGC-803细胞表现出最有效的抗增殖活性，IC 50值分别为1.67和1.88 μM。进一步的体外机制研究表明25q具有显着的抑制H1975细胞迁移的能力。此外，25q还将 H1975 细胞周期阻滞在 G0/G1 期并介导细胞凋亡。NO释放测定证实所设计的杂交体可以产生大量NO，并且NO释放能力和抗增殖活性之间具有一致的趋势。在这些化合物中，25q也表现出最有效的 NO 释放能力。总的来说，所有这些研究表明，设计的喹唑啉/苯磺酰呋喃杂化物具有显着的抗肿瘤活性和优异的NO释放能力，25q有潜力作为抗肿瘤药物开发的有价值的先导化合物。
• Novel Nitric Oxide-Releasing Derivatives of Farnesylthiosalicylic Acid: Synthesis and Evaluation of Antihepatocellular Carcinoma Activity
  作者：Yong Ling、Xiaolei Ye、Zhenzhen Zhang、Yihua Zhang、Yisheng Lai、Hui Ji、Sixun Peng、Jide Tian

  DOI：10.1021/jm1014814

  日期：2011.5.12

  Novel furoxan-based nitric oxide (NO) releasing derivatives (8a-p) of farnesylthiosalicylic acid (FTS) were synthesized. Compound 8l displayed the strongest inhibition on the proliferation of human hepatocellular carcinoma (HCC) cells in vitro, superior to FTS, sorafenib, and furoxan moiety, selectively induced high frequency of HCC cell apoptosis, and produced high levels of NO in HCC cells but not in nontumor liver cells. Furthermore, 8l exhibited low acute toxicity to mice and significantly inhibited the growth of HCC tumors in vivo and the Ras-related signaling in the tumors. Therefore, our novel findings may provide a new framework for the design of new NO-releasing furoxan/FTS hybrids for the intervention of human HCC.
• Novel Hybrids of (Phenylsulfonyl)furoxan and Anilinopyrimidine as Potent and Selective Epidermal Growth Factor Receptor Inhibitors for Intervention of Non-Small-Cell Lung Cancer
  作者：Chun Han、Zhangjian Huang、Chao Zheng、Ledong Wan、Lianwen Zhang、Sixun Peng、Ke Ding、Hongbin Ji、Jide Tian、Yihua Zhang

  DOI：10.1021/jm400463q

  日期：2013.6.13

  A series of hybrids (12a-k) from (phenylsulfonyl)furoxan and anilinopyrimidine were synthesized and biologically evaluated as epidermal growth factor receptor (EGFR) inhibitors for intervention of non-small-cell lung cancer (NSCLC). Compound 12k exhibited strong and selective EGFR L858R/T790M inhibitory activity (IC50 = 0.047 mu M) and displayed antiproliferative effects on EGFR mutation NSCLC cell lines HCC827 (del E746_A750) and H1975 (L858R/T790M) with IC50 values of 0.007 and 0.029 mu M, respectively. Additionally, 12k released high levels of NO in H1975 cells but not in normal human cells, and its activity was diminished by pretreatment with a NO scavenger. Furthermore, 12k induced apoptosis of H1975 and HCC827 cells more strongly than WZ4002 (1), inhibited EGFR downstream signaling in H1975 cells, and suppressed the nuclear factor-kappa B activation in H1975 cells, while 1 had no significant effects under the same conditions. Finally, 12k substantially inhibited tumor growth in an H1975 xenograft mouse model. Overall, 12k might be a promising candidate for the treatment of NSCLC.