3-((3-(Hydroxymethyl)phenoxy)methyl)-4-phenyl-1,2,5-oxadiazole 2-oxide | 454170-81-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 3-((3-(Hydroxymethyl)phenoxy)methyl)-4-phenyl-1,2,5-oxadiazole 2-oxide
• 英文别名: [3-[(2-oxido-4-phenyl-1,2,5-oxadiazol-2-ium-3-yl)methoxy]phenyl]methanol
• CAS: 454170-81-1
• 化学式: C₁₆H₁₄N₂O₄
• 分子量: 298.298
• InChiKey: GHPBXWKVMFZROI-UHFFFAOYSA-N

物化性质

• 沸点：
  537.9±60.0 °C(Predicted)
• 密度：
  1.30±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  22
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  81
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3-((3-(Hydroxymethyl)phenoxy)methyl)-4-phenyl-1,2,5-oxadiazole 2-oxide 在 三溴化磷 作用下， 以 二氯甲烷 为溶剂， 反应 1.17h， 以67.3%的产率得到C₁₆H₁₃BrN₂O₃
  参考文献：
  名称：

  Novel Nitric Oxide-Releasing Derivatives of Brusatol as Anti-Inflammatory Agents: Design, Synthesis, Biological Evaluation, and Nitric Oxide Release Studies

  摘要：

  Brusatol, a biologically active natural product, was modified in four distinct positions through the covalent attachment of a furoxan moiety, which acts as a nitric oxide (NO) donor. Forty derivatives were synthesized and evaluated for their inhibitory effects on excess NO biosynthesis in activated macrophages. Among them, compound 75 demonstrated inhibition (IC50 = 0.067 mu M) comparable to that of brusatol but were less cytotoxic. More importantly, even at very low doses (2 mu mol/kg/day), compound 75 also showed substantial inhibitory efficacy against chronic obstructive pulmonary disease (COPD)-like inflammation in the mouse model induced by cigarette smoke (CS) and lipopolysaccharide (LPS). Particularly, this compound was over 100-fold less toxic (LD50 > 3852 mu mol/kg) than brusatol and could be a promising lead for further studies. Notably, the improved properties of this derivative are associated with its NO-releasing capability.

  DOI：

  10.1021/jm5007534
• 作为产物：
  描述：

  3-(hydroxymethyl)-4-phenylfuroxan 在 吡啶 、 氯化亚砜 、 potassium carbonate 、 potassium iodide 作用下， 以 乙腈 为溶剂， 反应 24.0h， 生成 3-((3-(Hydroxymethyl)phenoxy)methyl)-4-phenyl-1,2,5-oxadiazole 2-oxide
  参考文献：
  名称：

  Discovery of novel hybrids of mTOR inhibitor and NO donor as potential anti-tumor therapeutics

  摘要：

  DOI：

  10.1016/j.bmc.2023.117402

文献信息

• Design, Synthesis, and Antihepatocellular Carcinoma Activity of Nitric Oxide Releasing Derivatives of Oleanolic Acid
  作者：Li Chen、Yihua Zhang、Xiangwen Kong、Edward Lan、Zhangjian Huang、Sixun Peng、Daniel L. Kaufman、Jide Tian

  DOI：10.1021/jm800167u

  日期：2008.8.1

  Novel furoxan-based nitric oxide (NO) releasing derivatives of oleanolic acid (OA) were synthesized for potential therapy of liver cancers. Six compounds produced high levels of NO in human hepatocellular carcinoma (HCC) cells and exhibited strong cytotoxicity selectively against HCC in vitro. Treatment with 8b or 16b significantly inhibited the growth of HCC tumors in vivo. These data provide a proof-in-principle

  合成了新型呋喃基一氧化氮 (NO) 释放齐墩果酸 (OA) 衍生物，用于肝癌的潜在治疗。六种化合物在人肝细胞癌 (HCC) 细胞中产生高水平的 NO，并在体外对 HCC 表现出强烈的细胞毒性。用 8b 或 16b 处理显着抑制了体内 HCC 肿瘤的生长。这些数据提供了原则上的证明，呋喃/OA 杂化物可用于人类肝癌的治疗干预。
• Design and synthesis of novel NO-donor-ferulic acid hybrids as potential antiatherosclerotic drug candidatesa
  作者：Nian-Guang Li、Rong Wang、Zhi-Hao Shi、Yu-Ping Tang、Bao-Quan Li、Zhen-Jiang Wang、Shu-Lin Song、Li-Hua Qian、Li Wei、Jian-Ping Yang、Li-Juan Yao、Jun-Zuan Xi、Jia Xu、Feng Feng、Da-Wei Qian、Jin-Ao Duan

  DOI：10.1002/ddr.20442

  日期：——

  Novel NO‐donor‐ferulic acid hybrids were designed and synthesized through a symbiotic approach using ferulic acid and three different NO‐donating groups, such as nitric ester, 4‐hydroxyl‐3‐phenylfuroxan, and 4‐hydroxymethyl‐3‐phenylsulfonylfuroxan. Antioxidant, nitric oxide release, and vasodilator properties studies showed that the target phenylsulfonylfuroxan 14, especially 14c, while keeping the

  通过使用阿魏酸和三个不同的NO供体基团（例如硝酸酯​​，4-羟基-3-苯基呋喃喃和4-羟基甲基-3-苯基磺酰呋喃喃）通过共生方法设计和合成了新型NO供体-阿魏酸杂交体。抗氧化剂，一氧化氮释放和血管舒张剂的性能研究表明，目标苯磺酰呋喃喃14（尤其是14c）在保持抗氧化剂活性的同时，显示出比硝酸异山梨酯（ISDN）更高的NO释放活性和血管舒张活性。因此，14c可能被认为是一种新型的有效抗动脉粥样硬化药物。Drug Dev Res 72：405–415，2011.©2011 Wiley‐Liss，Inc.
• 10.1691/ph.2015.4775
  作者：Bi, Yi、Yang, Jian、Ma, Cong、Liu, Ze-Yun、Zhang, Ting-Ting、Zhang, Xiao-Chen、Lu, Jing、Meng, Qing-Guo

  DOI：10.1691/ph.2015.4775

  日期：——
• Furoxan nitric oxide donor coupled chrysin derivatives: Synthesis and vasculoprotection
  作者：Xiao-Qing Zou、Sheng-Ming Peng、Chang-Ping Hu、Li-Feng Tan、Han-Wu Deng、Yuan-Jian Li

  DOI：10.1016/j.bmcl.2010.12.077

  日期：2011.2

  A series of furoxan-based nitric oxide-releasing chrysin derivatives were synthesized. Pharmacological assays indicated that all chrysin derivatives exhibited in vitro inhibitory activities against aldose reductase and advanced glycation end-product formation. Some chrysin derivatives were also found to increase the glucose consumption of HepG2 cells. Furthermore, the compounds released a low amount of NO in the presence of L-cysteine (range from 0.20% to 1.89%). These hybrid furoxan-based NO donor chrysin derivatives offer a mutual prodrug design concept for the development of therapeutic or preventive agents for vascular complications due to diabetes. (C) 2010 Elsevier Ltd. All rights reserved.
• Novel Nitric Oxide-Releasing Derivatives of Brusatol as Anti-Inflammatory Agents: Design, Synthesis, Biological Evaluation, and Nitric Oxide Release Studies
  作者：Weibin Tang、Jianlin Xie、Song Xu、Haining Lv、Mingbao Lin、Shaopeng Yuan、Jinye Bai、Qi Hou、Shishan Yu

  DOI：10.1021/jm5007534

  日期：2014.9.25

  Brusatol, a biologically active natural product, was modified in four distinct positions through the covalent attachment of a furoxan moiety, which acts as a nitric oxide (NO) donor. Forty derivatives were synthesized and evaluated for their inhibitory effects on excess NO biosynthesis in activated macrophages. Among them, compound 75 demonstrated inhibition (IC50 = 0.067 mu M) comparable to that of brusatol but were less cytotoxic. More importantly, even at very low doses (2 mu mol/kg/day), compound 75 also showed substantial inhibitory efficacy against chronic obstructive pulmonary disease (COPD)-like inflammation in the mouse model induced by cigarette smoke (CS) and lipopolysaccharide (LPS). Particularly, this compound was over 100-fold less toxic (LD50 > 3852 mu mol/kg) than brusatol and could be a promising lead for further studies. Notably, the improved properties of this derivative are associated with its NO-releasing capability.