4-(3-(hydroxymethyl)phenoxy)-3-(phenylsulfonyl)-1,2,5-oxadiazole 2-oxide | 452095-63-5

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 4-(3-(hydroxymethyl)phenoxy)-3-(phenylsulfonyl)-1,2,5-oxadiazole 2-oxide
• CAS: 452095-63-5
• 化学式: C₁₅H₁₂N₂O₆S
• 分子量: 348.336
• InChiKey: SKLYMWHKOKQVFG-UHFFFAOYSA-N

物化性质

• 沸点：
  583.6±60.0 °C(Predicted)
• 密度：
  1.50±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.43
• 重原子数：
  24.0
• 可旋转键数：
  5.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  116.57
• 氢给体数：
  1.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  4-(3-(hydroxymethyl)phenoxy)-3-(phenylsulfonyl)-1,2,5-oxadiazole 2-oxide 在 Jones reagent 作用下， 以 四氢呋喃 、 丙酮 为溶剂， 反应 11.5h， 生成
  参考文献：
  名称：

  设计，合成和抗肿瘤评估的新型组蛋白脱乙酰基酶抑制剂配备一氧化氮的苯磺酰呋喃喃模块。

  摘要：

  在创建多功能药物的策略的基础上，设计，合成和评估了一系列新的具有组蛋白脱乙酰基酶（HDAC）抑制和一氧化氮（NO）活性的基于苯磺酰呋喃酮的异羟肟酸酯。最有力的NO供体–HDAC抑制剂（HDACI）杂种5c对人类红白血病（HEL）细胞系的体外抗增殖活性比经批准的药物SAHA（Vorinostat）强得多，并且其抗增殖活性因NO清除剂血红蛋白呈剂量依赖性。进一步的机制研究表明5c在HEL细胞中强烈诱导细胞凋亡和G1期阻滞。动物实验确定5c在HEL细胞异种移植模型中具有有效的抗肿瘤活性的口服活性剂。有趣的是，尽管化合物5c在分子水平上具有显着的HDAC6选择性，但它在蛋白质印迹分析中显示出泛HDAC抑制作用，这很可能是由于在细胞水平上NO释放引起的I类HDACs抑制作用。

  DOI：

  10.1021/acs.jmedchem.5b00317
• 作为产物：
  描述：

  3-羟基苯甲醇 、 呋咱氮氧化物供体 在 sodium hydroxide 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 0.5h， 以74%的产率得到4-(3-(hydroxymethyl)phenoxy)-3-(phenylsulfonyl)-1,2,5-oxadiazole 2-oxide
  参考文献：
  名称：

  设计，合成和抗肿瘤评估的新型组蛋白脱乙酰基酶抑制剂配备一氧化氮的苯磺酰呋喃喃模块。

  摘要：

  在创建多功能药物的策略的基础上，设计，合成和评估了一系列新的具有组蛋白脱乙酰基酶（HDAC）抑制和一氧化氮（NO）活性的基于苯磺酰呋喃酮的异羟肟酸酯。最有力的NO供体–HDAC抑制剂（HDACI）杂种5c对人类红白血病（HEL）细胞系的体外抗增殖活性比经批准的药物SAHA（Vorinostat）强得多，并且其抗增殖活性因NO清除剂血红蛋白呈剂量依赖性。进一步的机制研究表明5c在HEL细胞中强烈诱导细胞凋亡和G1期阻滞。动物实验确定5c在HEL细胞异种移植模型中具有有效的抗肿瘤活性的口服活性剂。有趣的是，尽管化合物5c在分子水平上具有显着的HDAC6选择性，但它在蛋白质印迹分析中显示出泛HDAC抑制作用，这很可能是由于在细胞水平上NO释放引起的I类HDACs抑制作用。

  DOI：

  10.1021/acs.jmedchem.5b00317

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。
• 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.
• Synthesis and biological evaluation of nitric oxide-donating analogues of sulindac for prostate cancer treatment
  作者：Andrew Nortcliffe、Alexander G. Ekstrom、James R. Black、James A. Ross、Fouad K. Habib、Nigel P. Botting、David O’Hagan

  DOI：10.1016/j.bmc.2013.12.014

  日期：2014.1

  A series of analogues of the non-steroidal anti-inflammatory drug (NSAID) sulindac 1 were synthesised tethered to nitric oxide (NO) donating functional groups. Sulindac shows antiproliterative effects against immortal PC3 cell lines. It was previously demonstrated that the effect can be enhanced when tethered to NO releasing groups such as nitrate esters, furoxans and sydnonimines. To explore this approach further, a total of fifty-six sulindac-NO analogues were prepared and they were evaluated as NO-releasing cytotoxic agents against prostate cancer (PCa) cell lines. Compounds 1k and 1n exhibited significant cytotoxic with IC50 values of 6.1 +/- 4.1 and 12.1 +/- 3.2 mu M, respectively, coupled with observed nitric oxide release. (C) 2013 Elsevier Ltd. All rights reserved.
• Design, synthesis and evaluation of nitric oxide releasing derivatives of 2,4-diaminopyrimidine as novel FAK inhibitors for intervention of metastatic triple-negative breast cancer
  作者：Jinlin Zhang、Kangping Xu、Fei Yang、Yaoren Qiu、Jiayi Li、Jing Li、Wenxuan Wang、Guishan Tan、Zhenxing Zou、Fenghua Kang

  DOI：10.1016/j.ejmech.2023.115192

  日期：2023.3
• CN116425735
  申请人：——

  公开号：——

  公开（公告）日：——