4-(2-(methylamino)ethoxy)-3-(phenylsulfonyl)-1,2,5-oxadiazole-2-oxide | 1245575-39-6

• 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-(2-(methylamino)ethoxy)-3-(phenylsulfonyl)-1,2,5-oxadiazole-2-oxide
• 英文别名: 2-[[4-(benzenesulfonyl)-5-oxido-1,2,5-oxadiazol-5-ium-3-yl]oxy]-N-methylethanamine
• CAS: 1245575-39-6
• 化学式: C₁₁H₁₃N₃O₅S
• 分子量: 299.307
• InChiKey: QMSMGCYOGMHVLD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  20
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.27
• 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：

  4-(2-(methylamino)ethoxy)-3-(phenylsulfonyl)-1,2,5-oxadiazole-2-oxide 在 4-二甲氨基吡啶 、 N-羟基丁二酰亚胺 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 反应 25.0h， 生成 4-(2-(4-((1-((2R,4R,5R)-4-((tert-butyldimethylsilyl)oxy)-5-(((tert-butyldimethylsilyl)oxy)methyl)-3,3-difluorotetrahydrofuran-2-yl)-2-oxo-1,2-dihydropyrimidin-4-yl)amino)-N-methyl-4-oxobutanamido)ethoxy)-3-(phenylsulfonyl)-1,2,5-oxadiazole-2-oxide
  参考文献：
  名称：

  吉西他滨和苯磺酰呋喃类作为抗肿瘤剂的一氧化氮释放杂化物的合成和生物学评估†

  摘要：

  一系列的新型杂化10A-m的设计并合成了通过用偶联苯基磺酰基furoxans吉西他滨通过各种二醇或醇胺接头，并在体外评估了它们的生物学活性。大多数杂种表现出良好至中度的抗肿瘤活性，这与没有释放。尤其是，杂种10e表现出出色的抗癌活性，其功效比或与之相当吉西他滨。但是，抑制核苷转运只会显着降低其抑制率。吉西他滨对HepG2细胞但不10E，和抑制率10E通过用血红蛋白预处理进行部分还原，这表明的抗肿瘤活性10E可能会导致从高电平中的协同效应没有生产和吉西他滨片段。另外，化合物10e显然可以通过调节凋亡相关蛋白来诱导细胞凋亡。因此，我们的新发现为新呋喃喃/的设计提供了原理证明。吉西他滨 用于人类癌症干预的杂种。

  DOI：

  10.1039/c5md00158g
• 作为产物：
  描述：

  N-甲基-2-羟基乙胺 、 呋咱氮氧化物供体 反应 0.5h， 生成 4-(2-(methylamino)ethoxy)-3-(phenylsulfonyl)-1,2,5-oxadiazole-2-oxide
  参考文献：
  名称：

  吉西他滨和苯磺酰呋喃类作为抗肿瘤剂的一氧化氮释放杂化物的合成和生物学评估†

  摘要：

  一系列的新型杂化10A-m的设计并合成了通过用偶联苯基磺酰基furoxans吉西他滨通过各种二醇或醇胺接头，并在体外评估了它们的生物学活性。大多数杂种表现出良好至中度的抗肿瘤活性，这与没有释放。尤其是，杂种10e表现出出色的抗癌活性，其功效比或与之相当吉西他滨。但是，抑制核苷转运只会显着降低其抑制率。吉西他滨对HepG2细胞但不10E，和抑制率10E通过用血红蛋白预处理进行部分还原，这表明的抗肿瘤活性10E可能会导致从高电平中的协同效应没有生产和吉西他滨片段。另外，化合物10e显然可以通过调节凋亡相关蛋白来诱导细胞凋亡。因此，我们的新发现为新呋喃喃/的设计提供了原理证明。吉西他滨 用于人类癌症干预的杂种。

  DOI：

  10.1039/c5md00158g

文献信息

• Design, Synthesis and Biological Evaluation of Nitro Oxide Donating <i>N</i>-Hydroxycinnamamide Derivatives as Histone Deacetylase Inhibitors
  作者：Shiliang Tu、Hang Yuan、Jie Hu、Chengguang Zhao、Rui Chai、Hongfeng Cao

  DOI：10.1248/cpb.c14-00449

  日期：——

  Novel nitro oxide (NO)-donating N-hydroxycinnamamide derivatives 12a–j were designed and synthesized by coupling the carboxyl group of N-hydroxycinnamamides with phenylsulfonylfuroxan through various diols or alkylol amines, and their in vitro biological activities were evaluated. It was discovered that most of target compounds showed good histone deacetylases (HDACs) inhibition and anti-tumor activities, particularly for 12j, which had great HDACs inhibitory activities (IC50s=0.15–0.26 µM) and antiproliferative effects (IC50s=3.21–7.12 µM) comparable to suberoylanilide hydroxamic acid (SAHA) (IC50s=0.16–1.41 µM for HDACs, IC50s=3.15–7.45 µM for cancer cell inhibition). Furthermore, compound 12j with strong antitumor activities produced high levels of NO (up to 8.0 µM of nitrites/nitrates) in colon cancer cells, and its antiproliferative activity was nearly half-diminished by hemoglobin (10 µM), an NO scavenger. These results suggest that the strong antiproliferative activity of 12j could be attributed to the additive effects of high levels of NO production and inhibition of HDAC in the cancer cells.

  设计并合成了新颖的硝基氧（NO）供体N-羟基肉桂酰胺衍生物12a–j，通过各种二醇或烷醇胺将N-羟基肉桂酰胺的羧基与苯磺酰呋咱耦合，并评价了它们在体外的生物活性。研究发现，大多数目标化合物显示出良好的组蛋白去乙酰化酶（HDACs）抑制和抗肿瘤活性，特别是12j，其HDACs抑制活性（IC50s=0.15–0.26 µM）和抗增殖效应（IC50s=3.21–7.12 µM）与丁酸酰胺羟肟酸（SAHA）相当（HDACs的IC50s=0.16–1.41 µM，癌细胞抑制的IC50s=3.15–7.45 µM）。此外，具有强抗肿瘤活性的化合物12j在结肠癌细胞中产生高水平的NO（高达8.0 µM的亚硝酸盐/硝酸盐），其抗增殖活性几乎被血红蛋白（10 µM，一种NO清除剂）减半。这些结果表明，12j的强抗增殖活性可能归因于其在癌细胞中高水平NO产生和HDAC抑制的叠加效应。
• 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.
• Synthesis and in vitro biological evaluation of nitric oxide-releasing derivatives of hydroxylcinnamic acids as anti-tumor agents
  作者：Ming-Dong Lu、Xiao Zhou、Yao-Jun Yu、Pi-Hong Li、Wei-Jian Sun、Cheng-Guang Zhao、Zhi-Qiang Zheng、Tao You、Fei-Hai Wang

  DOI：10.1016/j.cclet.2013.03.006

  日期：2013.5

  Novel furoxan-based nitric oxide-releasing derivatives 6a-p of hydroxylcinnamic acids were synthesized by coupling the carboxyl group of hydroxylcinnamic acids with furoxan through various alkylol amines. Compounds 6a, e-i and m-p displayed more potent anti-tumor activities superior to control 5-fluorouracil (5-FU) in most cancer cells tested. Furthermore, 6f could selectively inhibit tumor cells, but not non-tumor cell proliferation. This inhibition was attributed to high levels of NO released in cancer cells and potentially synergistic effect of NO donor moieties and the bioactivity of hydroxylcinnamic acids. (C) 2013 Zhi-Qiang Zheng. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.