4-(4-(glycyloxy)butoxy)-3-(phenylsulfonyl)-1,2,5-oxadiazole 2-oxide | 1236359-12-8

• 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-(glycyloxy)butoxy)-3-(phenylsulfonyl)-1,2,5-oxadiazole 2-oxide
• CAS: 1236359-12-8
• 化学式: C₁₄H₁₇N₃O₇S
• 分子量: 371.371
• InChiKey: JOMRZVUXGLOHCW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.2
• 重原子数：
  25.0
• 可旋转键数：
  9.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  148.66
• 氢给体数：
  1.0
• 氢受体数：
  9.0

反应信息

• 作为反应物：
  描述：

  4-(4-(glycyloxy)butoxy)-3-(phenylsulfonyl)-1,2,5-oxadiazole 2-oxide 、 2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oyl chloride 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 12.0h， 生成 4-[[4-(benzenesulfonyl)-5-oxido-1,2,5-oxadiazol-5-ium-3-yl]oxy]butyl 2-[[(4aS,6aR,6bS,8aR,12aS,14aR,14bS)-11-cyano-2,2,6a,6b,9,9,12a-heptamethyl-10,14-dioxo-1,3,4,5,6,7,8,8a,14a,14b-decahydropicene-4a-carbonyl]amino]acetate
  参考文献：
  名称：

  Synthesis of CDDO–Amino Acid–Nitric Oxide Donor Trihybrids as Potential Antitumor Agents against Both Drug-Sensitive and Drug-Resistant Colon Cancer

  摘要：

  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.

  DOI：

  10.1021/jm5019302
• 作为产物：
  描述：

  4-(4-(2-(tert-butoxycarbonylamino)acetoxy)butoxy)-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)butoxy)-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

文献信息

• Design, synthesis and cytotoxic evaluation of nitric oxide-releasing derivatives of isosteviol
  作者：Yan Liu、Tingting Wang、Yong Ling、Na Bao、Wei Shi、Li Chen、Jianbo Sun

  DOI：10.1111/cbdd.12956

  日期：2017.9

  Twenty‐six novel isosteviol derivatives coupled with two types of nitric oxide (NO) donors (furoxans and NONOates) were synthesized and screened for cytotoxic activities against four human cancer cell lines with sunitinib as the positive control. The results showed that seven furoxan‐based derivatives (8a, 8b, 8c, 8d, 8e, 9e, and 9f) exhibited desirable cytotoxic activities, while NONOate‐based derivatives displayed poor potency because of unstability. Compared with sunitinib, compounds 8a and 8e were more active on all tested cell lines, especially in HCT116 (8a, IC50 = 0.48 ± 0.02 μm; 8e, IC50 = 0.94 ± 0.01 μm); compounds 8b and 8d were more potent on HCT116 (IC50 = 3.39 ± 0.06 and 3.29 ± 0.03 μm), HepG2 (IC50 = 1.05 ± 0.03 and 5.37 ± 0.08 μm), and SW620 (IC50 = 1.33 ± 0.02 and 4.11 ± 0.05 μm) cell lines, and 8c exhibited higher activities on HepG2 cells with an IC50 = 4.76 ± 0.14 μm. NO‐releasing experiment of compounds 8a–e, 17a, 18a, 19a, and 21a reminded us that NO‐releasing amount of this series of isosteviol derivatives positively correlates with their cytotoxic activities.