3-(氯甲基)-4-苯基-1,2,5-噁二唑 2-氧化物 | 217966-10-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 中文名称: 3-(氯甲基)-4-苯基-1,2,5-噁二唑 2-氧化物
• 中文别名: 3-(氯甲基)-4-苯基-1,2,5-噁二唑2-氧化物
• 英文名称: 3-(chloromethyl)-4-phenyl-1,2,5-oxadiazole 2-oxide
• 英文别名: 3-(chloromethyl)-2-oxido-4-phenyl-1,2,5-oxadiazol-2-ium
• CAS: 217966-10-4
• 化学式: C₉H₇ClN₂O₂
• 分子量: 210.62
• InChiKey: NREYEXWRWAMJMT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  51.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-(氯甲基)-4-苯基-1,2,5-噁二唑 2-氧化物 在 1-羟基苯并三唑 、 caesium carbonate 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三氟乙酸 、 potassium iodide 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成 (2-oxido-4-phenyl-1,2,5-oxadiazol-2-ium-3-yl)methyl (2S)-2-[[4-[(5,5,8,8-tetramethyl-6,7-dihydronaphthalen-2-yl)carbamoyl]benzoyl]amino]propanoate
  参考文献：
  名称：

  Novel antileukemic agents derived from tamibarotene and nitric oxide donors

  摘要：

  A series of novel nitric oxide-releasing tamibarotene derivatives were synthesized by coupling nitric oxide (NO) donors with tamibarotene via various spacers, and were evaluated for their antiproliferative activities against human leukemic HL-60, NB4 and K562 cell lines in vitro. The test results showed that three compounds (7g, 9a and 9e) exhibited more potent antileukemic activity than the control tamibarotene. Furthermore, the preliminary structure-activity analysis revealed that amino acids serving as spacers could bring about significantly improved biological activities of NO donor hybrids. These interesting results could provide new insights into the development of NO-based antileukemic agents. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.09.103
• 作为产物：
  描述：

  cinnamic alcohol 在 氯化亚砜 、 sodium nitrite 作用下， 反应 48.0h， 生成 3-(氯甲基)-4-苯基-1,2,5-噁二唑 2-氧化物
  参考文献：
  名称：

  Design, Synthesis, and Pharmacological Evaluation of Novel Hybrid Compounds to Treat Sickle Cell Disease Symptoms. Part II: Furoxan Derivatives

  摘要：

  Phthalimide derivatives containing furoxanyl subunits as nitric oxide (NO)-donors (3a-g) were designed, synthesized, and evaluated in vitro and in vivo for their potential uses in the oral treatment of sickle cell disease symptoms. All compounds (3a-g) demonstrated NO-donor properties at different levels. Moreover, compounds 3b and 3c demonstrated analgesic activity. Compound 3b was determined to be a promising drug candidate for the aforementioned uses, and it was further evaluated in K562 culture cells to determine its ability to increase levels of gamma-globin expression. After 96 h at 5 mu M, compound 3b was able to induce gamma-globin expression by nearly three times. Mutagenic studies using micronucleus tests in peripheral blood cells of mice demonstrated that compound 3b reduces the mutagenic profile as compared with hydroxyurea. Compound 3b has emerged as a new leading drug candidate with multiple beneficial effects for the treatment of sickle cell disease symptoms and provides an alternative to hydroxyurea treatment.

  DOI：

  10.1021/jm300602n

文献信息

• 鸦胆苦醇衍生物及其在炎症和免疫功能紊乱 疾病中的用途
  申请人：中国医学科学院药物研究所

  公开号：CN104844617B

  公开（公告）日：2019-01-01

  本发明公开了一类鸦胆苦醇衍生物及其在炎症和免疫功能紊乱疾病中的用途。具体涉及一类一氧化氮供体鸦胆苦醇衍生物或其医学上可接受的盐，含有这些衍生物的药用组合物以及它们在制备抗炎和免疫抑制药物中的应用。在制备炎症和/或免疫紊乱相关疾病药物中的应用。
• A Novel Parkinson’s Disease Drug Candidate with Potent Anti-neuroinflammatory Effects through the Src Signaling Pathway
  作者：Ya-Dan Wang、Xiu-Qi Bao、Song Xu、Wen-Wen Yu、Sheng-Nan Cao、Jin-Ping Hu、Yan Li、Xiao-Liang Wang、Dan Zhang、Shi-Shan Yu

  DOI：10.1021/acs.jmedchem.6b00976

  日期：2016.10.13

  mice at a median lethal dose (LD50) >5000 mg/kg. Its in vivo efficacy was demonstrated in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)- and MPTP/probenecid (prob)-induced subacute and chronic PD models, respectively, and α-synuclein transgenic mice. Mechanistic studies revealed neuroinflammation inhibition by targeting Src/phosphatase and tensin homologue deleted on chromosome 10 (PTEN)/Akt signaling

  帕金森氏病（PD）是一种与年龄有关的神经退行性疾病，目前有许多药物治疗方法，但大多数都会引起严重的副作用。因此，迫切需要能够阻止疾病进展并允许长期给药的新型治疗策略。神经炎症在PD的发病机理中起关键作用。在这里，我们报告发现和优化间苯三酚衍生物，一类新型的抗神经炎化合物。对命中化合物3-甲基-1-（2,4,6-三羟基苯基）丁-1-的结构修饰产生了43种衍生物，包括临床前候选药物（化合物21），具有良好的体外抗神经炎作用，具有良好的体外抗炎性。在中等致死剂量下小鼠血脑屏障穿透力和理想的安全裕度（LD 50）> 5000 mg / kg。分别在1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）-和MPTP / probenecid（prob）诱导的亚急性和慢性PD模型以及α-突触核蛋白转基因模型中证明了其体内功效老鼠。机理研究表明，通过靶向10号染色体（PTEN）/ Akt信号缺失的Src
• Synthesis and Herbicidal Activity of <i>N</i>-Oxide Derivatives
  作者：Hugo Cerecetto、Eduardo Dias、Rossanna Di Maio、Mercedes González、Sandra Pacce、Patricia Saenz、Gustavo Seoane、Leopoldo Suescun、Alvaro Mombrú、Grisel Fernández、Marisa Lema、Juana Villalba

  DOI：10.1021/jf9904766

  日期：2000.7.1

  As part of an ongoing program on the chemistry and biological activity of N-oxide-containing molecules, a number of novel 1,2, 5-oxadiazole N-oxide, benzo[1,2-c]1,2,5-oxadiazole N-oxide, and quinoxaline N,N'-dioxide derivatives were synthesized and evaluated for their herbicidal activity. Many of these compounds exhibited moderate to good herbicidal pre-emergence activity against Triticum aestivum

  作为正在进行的有关含氮氧化物分子化学和生物学活性的计划的一部分，许多新型的1,2,5-恶二唑N-氧化物，苯并[1,2-c] 1,2,5-恶二唑合成了N-氧化物和喹喔啉N，N'-二氧化物衍生物，并对其除草活性进行了评估。这些化合物中有许多对普通小麦表现出中等至良好的除草前出苗活性。在更具代表性的化合物（12、20和26）上进行了剂量反应研究。活性最强的丁基氨基甲酰基苯并[1,2-c] 1,2,5-恶二唑N-氧化物26在低至24 g / ha的浓度下表现出除草活性。
• Synthesis and E-Beam-Mediated Gas Phase Fragmentation of Thiol-Containing Furoxans for Nanopatterned Alkyne Formation on Gold Surface
  作者：Hyun-Seo Koo、Kyung-Moon Park、Kwang-Jin Hwang

  DOI：10.5012/bkcs.2010.31.12.3583

  日期：2010.12.20

  Furoxanthiols PFT and BPFT possessing thiomethyl or thiobenzyl groups in the furoxan ring were designed and synthesized as potential light-sensitive alkyne precursors on a gold surface. The synthesis of thiofuroxans PFT and BPFT was performed from the corresponding halofuroxans 1b and 2c, respectively, by the substitution with potassium thioacetate in ethyl acetate/ethanol or DMF, followed by basic hydrolysis as the key reactions. Electron-beammediated fragmentation of furoxans 1c and 2d in a mass spectrometer afforded the corresponding aryl alkyne fragments, with the evolution of NO in high preference. In the cases of thiofuroxans PFT and BPFT, carbon-sulfur bond cleavage was observed as a representative fragmentation, producing M-SH and M-SAc peaks, which competed with the release of NO. In the fragmentation of mono-aryl furoxan 1c, the release of molecule of NO was predominately observed to produce an M-NO fragment as a base peak by the formation of trimembered thiiranium or azirine intermediate.

  我们设计并合成了呋喃环上具有硫代甲基或硫代苄基的呋喃黄原酮 PFT 和 BPFT，作为金表面潜在的光敏炔前体。硫代呋喃类化合物 PFT 和 BPFT 的合成分别以相应的卤代呋喃类化合物 1b 和 2c 为原料，在乙酸乙酯/乙醇或 DMF 中用硫代乙酸钾取代，然后以碱性水解作为关键反应。在质谱仪中对呋喃 1c 和 2d 进行电子束介导碎裂，可得到相应的芳基炔烃片段，其中以 NO 的进化最为优先。在硫代呋喃类化合物 PFT 和 BPFT 中，碳-硫键裂解是一种代表性的碎裂，产生 M-SH 和 M-SAc 峰，与 NO 的释放形成竞争。在单芳基呋喃 1c 的破碎过程中，主要观察到 NO 分子的释放，通过形成三元噻吩或氮丙啶中间体，产生 M-NO 片段作为基峰。
• 一种多靶点抗肿瘤维甲酸类衍生物及其合成方法和应用
  申请人：成都大学

  公开号：CN112390765A

  公开（公告）日：2021-02-23

  本发明提供了一种多靶点抗肿瘤维甲酸类衍生物及其合成方法和应用。本发明基于多靶点药物理论为指导，以Am580为母核并结合其结构特点选择了呋咱氮(Furoxans)类NO供体作为NO源，通过对该NO供体进行化学修饰，得到一系列不同的供体，再通过脂或者酰胺键与母核偶联，合成了一系列新型的多靶点维甲酸衍生物，结果表明该类多靶点维甲酸衍生物的活性更高，毒副作用更低，抗肿瘤效果更好。本发明提供的多靶点抗肿瘤维甲酸类衍生物的结构通式如式(Ⅰ)：