4-(3-hydroxy-3-methylbutoxy)-3-(phenylsulfonyl)-1,2,5-oxadiazole 2-oxide | 1357152-12-5

• 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-(3-hydroxy-3-methylbutoxy)-3-(phenylsulfonyl)-1,2,5-oxadiazole 2-oxide
• CAS: 1357152-12-5
• 化学式: C₁₃H₁₆N₂O₆S
• 分子量: 328.346
• InChiKey: JORBGYKZVXEFPX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.68
• 重原子数：
  22.0
• 可旋转键数：
  6.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.38
• 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-hydroxy-3-methylbutoxy)-3-(phenylsulfonyl)-1,2,5-oxadiazole 2-oxide 在 4-二甲氨基吡啶 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 1,4-二氧六环 、 二氯甲烷 为溶剂， 生成 Methyl 4-[5-[1-[2-[4-[[4-(benzenesulfonyl)-5-oxido-1,2,5-oxadiazol-5-ium-3-yl]oxy]-2-methylbutan-2-yl]oxy-2-oxoethyl]piperidin-4-yl]oxycarbonyl-7-methoxy-1,3-benzodioxol-4-yl]-7-methoxy-1,3-benzodioxole-5-carboxylate
  参考文献：
  名称：

  Potent Inhibition of Nitric Oxide-Releasing Bifendate Derivatives against Drug-Resistant K562/A02 Cells in Vitro and in Vivo

  摘要：

  Multidrug resistance is a major obstacle to successful chemotherapy for leukemia. In this study; a series of nitric oxide (NO)-releasing bifendate derivatives (7a-n) were synthesized. Biological evaluation indicated that the most active compound (7a) produced relatively high levels of NO and significantly inhibited the proliferation of drug-resistant K562/A02 cells in vitro and in-vivo. In addition, 7a induced the mitochondrial tyrosine nitration and the intracellular accumulation of rhodamine 123 by inhibiting P-gp activity in K562/A02 cells. Furthermore, 7a remarkably down-regulated AKT, NF-kappa B, and ERK activation and HIF-1 alpha expression in K562/A02 cells, which are associated with the tumor cell proliferation and drug resistance. Notably, the antitumor effects were dramatically attenuated by an NO scavenger or elimination of the NO-releasing capability of 7a, indicating that NO produced by 7a contributed to, at least partly, its cytotoxicity against drug-resistant K562/A02 cells. Overall, 7a may be a potential agent against drug-resistant myelogenous leukemia.

  DOI：

  10.1021/acs.jmedchem.6b01075
• 作为产物：
  描述：

  异戊二醇 、 呋咱氮氧化物供体 在 sodium hydroxide 作用下， 以 四氢呋喃 为溶剂， 反应 0.5h， 生成 4-(3-hydroxy-3-methylbutoxy)-3-(phenylsulfonyl)-1,2,5-oxadiazole 2-oxide
  参考文献：
  名称：

  Synthesis and evaluation of nitric oxide-releasing DDB derivatives as potential Pgp-mediated MDR reversal agents in MCF-7/Adr cells

  摘要：

  Novel furoxan-based nitric oxide (NO)-releasing DDB derivatives (7a-j) were synthesized. Compounds 7i and 7j significantly reversed the resistance of MCF-7/Adr cells to doxorubicin in the combination treatment, and markedly increased the intracellular accumulation of doxorubicin probably via inhibiting Pgp-mediated intracellular drug efflux as well as down-regulating doxorubicin-induced Pgp expression. It was demonstrated that NO released by 7i and 7j played an important role in increasing intracellular doxorubicin accumulation and chemo-sensitizing MCF-7/Adr cells to doxorubicin, and the synergic effects of DDB and NO-donor moieties in 7i and 7j may contribute to reversing Pgp-mediated MDR in MCF-7/Adr cells to doxorubicin. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.12.065