4-(4-(2-(tert-butoxycarbonylamino)acetoxy)but-2-ynyloxy)-3-(phenylsulfonyl)-1,2,5-oxadiazol-2-oxide | 1229581-41-2

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 4-(4-(2-(tert-butoxycarbonylamino)acetoxy)but-2-ynyloxy)-3-(phenylsulfonyl)-1,2,5-oxadiazol-2-oxide
• CAS: 1229581-41-2
• 化学式: C₁₉H₂₁N₃O₉S
• 分子量: 467.456
• InChiKey: MHZPVMCAZKCELP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.59
• 重原子数：
  32.0
• 可旋转键数：
  7.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  160.97
• 氢给体数：
  1.0
• 氢受体数：
  10.0

反应信息

• 作为反应物：
  描述：

  4-(4-(2-(tert-butoxycarbonylamino)acetoxy)but-2-ynyloxy)-3-(phenylsulfonyl)-1,2,5-oxadiazol-2-oxide 在 三氟乙酸 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 生成 4-((4-(glycyloxy)but-2-yn-1-yl)oxy)-3-(phenylsulfonyl)-1,2,5-oxadiazole 2-oxide
  参考文献：
  名称：

  法呢基硫代水杨酸释放一氧化氮的衍生物作为抗肿瘤药的合成与评价

  摘要：

  合成了法呢基硫代水杨酸（FTA）的新型基于呋喃烷的一氧化氮（NO）释放衍生物（11a – p）。在大多数测试的癌细胞中，化合物11d，11f，11k和11m - o表现出优于FTA和索拉非尼的抗肿瘤活性。对六种化合物的分析显示，具有低抗肿瘤活性的11d，11f，11n，11o和11p而不是11a产生高水平的NO，这与它们的强抗肿瘤活性有关。此外，11f的抗肿瘤活性呋喃喃部分模拟了部分被氧化，但被血红蛋白预处理减少了。重要的是，用11f治疗可抑制癌细胞中与Ras相关的信号传导。显然，11f的高抗肿瘤活性归因于癌细胞中高水平的NO产生和Ras相关信号的抑制的协同作用。我们的发现表明，呋喃喃/ FTA杂种作为治疗人类癌症的治疗剂可能具有更大的前景。

  DOI：

  10.1016/j.bmc.2010.03.077
• 作为产物：
  描述：

  二碳酸二叔丁酯 在 4-二甲氨基吡啶 、 N,N'-二环己基碳二亚胺 、 sodium hydroxide 、 叔丁醇 作用下， 以 二氯甲烷 、 水 为溶剂， 反应 48.0h， 生成 4-(4-(2-(tert-butoxycarbonylamino)acetoxy)but-2-ynyloxy)-3-(phenylsulfonyl)-1,2,5-oxadiazol-2-oxide
  参考文献：
  名称：

  Novel NO-releasing derivatives of betulinic acid with antitumor activity

  摘要：

  Thirteen novel NO-releasing derivatives of betulinic acid (BA) bearing two types of NO-donors (nitrates and furoxans) were synthesized and evaluated for their antitumor activity. The results showed that furoxan-based derivatives exhibited higher antitumor activity than nitrate-based derivatives, with compounds 11a and 11b displaying promising potency against B16 cell lines and HepG2 cell lines (IC50 < 1 mu mol/L). We supposed that NO-releasing amount of these derivatives which can be detected by Griess method may contribute more to their antitumor activity. As a result, furoxan-based derivatives released larger amount of NO than that of nitrate-based derivatives, which partially explained the higher anti-tumor activity of the former. (C) 2015 Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences. Published by Elsevier B.V. All rights reserved.

  DOI：

  10.1016/j.cclet.2015.04.002

文献信息

• Synthesis and biological evaluation of furoxan-based nitric oxide-releasing derivatives of glycyrrhetinic acid as anti-hepatocellular carcinoma agents
  作者：Yisheng Lai、Lihong Shen、Zhenzhen Zhang、Wenqing Liu、Yihua Zhang、Hui Ji、Jide Tian

  DOI：10.1016/j.bmcl.2010.09.070

  日期：2010.11

  A series of novel furoxan-based nitric oxide (NO)-releasing derivatives of glycyrrhetinic acid (GA) were designed, synthesized, and evaluated for their in vitro cytotoxicity against human hepatocellular carcinoma (HCC) and non-tumor liver cells. Five furoxan/GA hybrids, 7b-d, 7f, and 7g, displayed potent cytotoxicity against HCC cells (IC(50): 0.25-1.10 mu M against BEL-7402 cells and 1.32-6.78 mu M against HepG2 cells), but had a little effect on the growth of LO2 cells, indicating that these compounds had selective cytotoxicity against HCC cells. Furthermore, these compounds produced high concentrations of NO in HCC cells, but low in LO2 cells and treatment with hemoglobin partially reduced the cytotoxicity of the hybrid in HCC cells. Apparently, the high concentrations of NO produced by NO donor moieties and the bioactivity of GA synergistically contribute to the cytotoxicity, but the NO is a major player against HCC cells in vitro. Potentially, our findings may aid in the design of new chemotherapeutic reagents for the intervention of human HCC at clinic. (C) 2010 Elsevier Ltd. All rights reserved.
• Synthesis of CDDO–Amino Acid–Nitric Oxide Donor Trihybrids as Potential Antitumor Agents against Both Drug-Sensitive and Drug-Resistant Colon Cancer
  作者：Yong Ai、Fenghua Kang、Zhangjian Huang、Xiaowen Xue、Yisheng Lai、Sixun Peng、Jide Tian、Yihua Zhang

  DOI：10.1021/jm5019302

  日期：2015.3.12

  Seventeen CDDO-amino acid-NO donor trihybrids (4a-q) were designed and synthesized. Biological evaluation indicated that the most active compound 4c produced high levels of NO and inhibited the proliferation of drug-sensitive (HCT-8, IC50 = 0.294 mu M) and drug-resistant (HCT-8/5-FU, IC50 = 0.232 mu M) colon cancer cells, which were attenuated by an NO scavenger or typical substrate of PepT1. Furthermore, 4c triggered HCT-8 and HCT-8/5-FU cell apoptosis more strongly than CDDO-Me, inhibited the HIF-1a, Stat3, AKT, and ERK signaling, and induced the nitration of P-gp, MRP1, and BCRP proteins in HCT-8/5-FU cells. Finally, 4c had 4.36-5.53-fold less inhibitory activity against nontumor colon epithelial-like cells (CCD841, IC50 = 1.282 mu M) in vitro and inhibited the growth of implanted human drug-resistant colon cancers in mice more potently than CDDO-Me. Together, 4c is a novel trihybrid with potent antitumor activity and may be a promising candidate for the treatment of drug-resistant colon cancer.