5-(azidomethyl)-3-(4-methoxyphenyl)isoxazole | 1262439-59-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 5-(azidomethyl)-3-(4-methoxyphenyl)isoxazole
• 英文别名: 5-(Azidomethyl)-3-(4-methoxyphenyl)-1,2-oxazole
• CAS: 1262439-59-7
• 化学式: C₁₁H₁₀N₄O₂
• 分子量: 230.226
• InChiKey: YQGSNIOIVUOMMI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  49.6
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  5-(azidomethyl)-3-(4-methoxyphenyl)isoxazole 在 三苯基膦 作用下， 以 四氢呋喃 、 水 为溶剂， 生成 [3-(4-Methoxyphenyl)-1,2-oxazol-5-yl]methanamine;hydrochloride
  参考文献：
  名称：

  Synthesis of new secretory phospholipase A2-inhibitory indole containing isoxazole derivatives as anti-inflammatory and anticancer agents

  摘要：

  Secretory phospholipase A(2) (sPLA(2)) is an important enzyme that plays a key role in various inflammatory diseases including cancer and its inhibitors have been developed as preventive or therapeutic agents. In the present study, a series of new indole containing isoxazole derivatives (10a-10o) is synthesized and evaluated for their sPLA(2) inhibitory activities. All compounds (10a-10o) showed significant sPLA(2) inhibition activities both in vitro and in vivo studies which is substantiated in in silico studies. Among all the tested compounds, 100 showed potent sPLA(2) inhibition activity, that is comparable or more to ursolic acid (positive control). Further studies demonstrated that 100 showed in vitro antiproliferative activity when tested against MCF-7 breast and DU145 prostate cancer cells. Furthermore, compounds 10a-10o obeyed lipinsky's rule of 5 and suggesting druggable properties. The in vitro, in vivo and in silico results are encouraging and warrant pre-clinical studies to develop sPLA(2)-inhibitory compound 10o as novel therapeutic agent for various inflammatory disorders and several malignancies. (C) 2016 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2016.02.025
• 作为产物：
  描述：

  对甲氧基苯甲醛肟 在 N-氯代丁二酰亚胺 、 sodium azide 、 碳酸氢钠 、 potassium carbonate 、 copper(II) sulfate 、 sodium ascorbate 、 三乙胺 作用下， 以 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.31h， 生成 5-(azidomethyl)-3-(4-methoxyphenyl)isoxazole
  参考文献：
  名称：

  设计和合成对克鲁斯锥虫和亚马逊利什曼原虫有活性的3,5-二取代异恶唑的新系列

  摘要：

  恰加斯病和利什曼病是发展中国家中被忽视的热带病（NTD）。尽管有可用于治疗的药物，但是寻找新的有效疗法的努力仍在继续。天然木脂素Grandisin（1）和veraguensin（2）表现出对抗锥虫T. cruzi的活性，其脚手架已被启发用于设计具有更高效价和化学性质的新衍生物。我们在这里基于木脂素1和2的结构描述26种异恶唑衍生物的计划和微波辐射合成。此外，体外评估培养的锥虫和胞内变形虫的抗性。据报道，亚马逊乳杆菌和婴儿乳杆菌的克鲁氏锥虫和胞内变形虫。中合成的衍生物，化合物17（IC 50  = 5.26μM为克氏锥虫），29（IC 50  = 1.74μM为锥虫）和31（IC 50  = 1.13μM为锥虫和IC 50  = 5.08μM为亚马逊乳杆菌（L. amazonensis）是最活跃的，并且在其作用机理的初步研究中还针对抗克鲁斯氏锥虫的重组锥虫硫醚还原酶进行了评估。

  DOI：

  10.1016/j.ejmech.2017.01.029

文献信息

• Discovery, Synthesis, and Biological Evaluation of a Novel Group of Selective Inhibitors of Filoviral Entry
  作者：Maria V. Yermolina、Jizhen Wang、Michael Caffrey、Lijun L. Rong、Duncan J. Wardrop

  DOI：10.1021/jm1008715

  日期：2011.2.10

  Herein, we report the development of an antifiloviral screening system, based on a pseudotyping strategy, and its application in the discovery of a novel group of small molecules that selectively inhibit the Ebola and Marburg glycoprotein (GP)-mediated infection of human cells. Using Ebola Zaire GP-pseudotyped HIV particles bearing a luciferase reporter gene and 293T cells, a library of 237 small molecules

  在此，我们报告了基于假型策略的抗丝病毒筛选系统的开发，及其在发现一组新的小分子中的应用，这些小分子选择性地抑制了埃博拉病毒和马尔堡糖蛋白 (GP) 介导的人类细胞感染。使用带有荧光素酶报告基因和 293T 细胞的 Ebola Zaire GP 假型 HIV 颗粒，筛选了 237 个小分子库以抑制 GP 介导的病毒进入。从该测定中，先导化合物8a被鉴定为丝状病毒进入的选择性抑制剂，IC 5030 μM。为了分析功效的官能团要求，然后使用“点击”化学制备的 56 种异恶唑和三唑衍生物对这种 3,5-二取代异恶唑进行结构-活性关系分析。该研究表明，虽然异恶唑环可以被三唑系统取代，但在8a 中发现的 5-（二乙氨基）乙酰胺取代基是抑制病毒细胞进入所必需的。3-芳基取代基的变化提供了许多更有效的抗病毒剂，IC 50值范围为2.5 μM。还发现先导化合物8a及其三种衍生物可阻断马尔堡糖蛋白 (GP) 介导的人类细胞感染。
• Synthesis and SAR of new isoxazole-triazole bis-heterocyclic compounds as analogues of natural lignans with antiparasitic activity
  作者：Lara A. Zimmermann、Milene H. de Moraes、Rafael da Rosa、Eduardo B. de Melo、Fávero R. Paula、Eloir P. Schenkel、Mario Steindel、Lílian S.C. Bernardes

  DOI：10.1016/j.bmc.2018.08.025

  日期：2018.9

  qualitative structure activity relationship study using three dimensional descriptors was carried out and showed a correlation between growth inhibitory potency and the presence of bulky hydrophobic groups located at rings A and D of the compounds. Compound 3-(3,4-dimethoxyphenyl)-5-((4-(4-pentylphenyl)-1H-1,2,3-triazol-1-yl)methyl)isoxazole (31) was the most active in the series (GI50 12.2 μM), showing, in

  尽管近几十年来科学技术取得了令人瞩目的进步，但目前尚无有效的治疗南美锥虫病的方法。我们的研究小组一直在研究天然木脂素类似物的设计和合成，旨在鉴定具有抗寄生虫活性的化合物。本文报道了42种新颖的双杂环衍生物的合成以及基于克氏锥虫锥虫生物学检测结果的结构-活性关系研究。有37种活性化合物，其中8种的GI 50值低于100μM（GI 5088.4–12.2μM）。进行了使用三维描述符的定性结构活性关系研究，结果表明生长抑制能力与位于化合物环A和D处的大疏水基团的存在之间存在相关性。化合物3-（3,4-二甲氧基苯基）-5-（（4-（4-戊基苯基）-1H-1,2,3-三唑-1-基）甲基）异恶唑（31）是该系列中最活跃的化合物（GI 50 12.2μM ），在体外显示出与苯硝唑（GI 50 10.2μM）相似的低毒性和强效性。这些结果表明，该化合物可能是设计新型锥虫杀伤性化合物的有前途的支架。
• Synthesis and biological evaluation of isoxazolyl-sulfonamides: A non-cytotoxic scaffold active against Trypanosoma cruzi, Leishmania amazonensis and Herpes Simplex Virus
  作者：Rafael da Rosa、Lara Almida Zimmermann、Milene Höehr de Moraes、Naira Fernanda Zanchett Schneider、Alice Duarte Schappo、Claudia Maria de Oliveira Simões、Mario Steindel、Eloir Paulo Schenkel、Lílian Sibelle Campos Bernardes

  DOI：10.1016/j.bmcl.2018.08.040

  日期：2018.11

  In this study we report the synthesis, characterization, biological evaluation, and druglikeness assessment of a series of 20 novel isoxazolyl-sulfonamides, obtained by a four-step synthetic route. The compounds had their activity against Trypanosoma cruzi, Leishmania amazonensis, Herpes Simplex Virus type 1 and cytotoxicity evaluated in phenotypic assays. All compounds have drug-like properties, showed

  在这项研究中，我们报告了通过四步合成途径获得的一系列20种新型异恶唑基磺酰胺的合成，表征，生物学评估和药物相似性评估。该化合物具有抗克氏锥虫，亚马逊利什曼原虫，单纯疱疹病毒1型的活性，并在表型分析中评估了细胞毒性。所有化合物均具有药物样性质，显示出低细胞毒性，并且对于本文报道的所有其他生物活性，特别是针对克鲁氏锥虫的抑制活性，它们是有希望的。化合物8和16表现出显着的效价和对克氏锥虫（GI 50 分别为14.3 µM，SI> 34.8和GI 50  = 11.6 µM，SI = 29.1）。这些值接近于参考药物苯硝唑的值（GI 50  = 10.2 µM），表明化合物8和16代表了有希望的候选物，可用于进一步针对南美锥虫病的临床前开发。
• Magnetically separable new Fe3O4@AgZr2(PO4)3 nanocomposite catalyst for the synthesis of novel isoxazole/isoxazoline-linked 1,2,3-triazoles in water under ultrasound cavitation
  作者：Loubna Mokhi、Ali Moussadik、Mohsine Driowya、Ayoub El Mahmoudi、Hamza Tachallait、Rachid Benhida、Adnane El Hamidi、Khalid Bougrin

  DOI：10.1016/j.molliq.2023.123763

  日期：2024.2

  indicate that FeO particles ranging in size from 50 to 75 nm were evenly distributed on the surface of AgZr(PO). The use of an aqueous reaction medium, the simple and inexpensive recovery of the catalyst by the application of an external magnet and the high and constant catalytic efficiency over at least five consecutive cycles make this protocol more interesting from an operational point of view.

  在这项工作中，我们报道了一种新型磁分离FeO@AgZr(PO)作为非均相纳米复合催化剂，用于超声空化下水中的一锅四步级联磺酰化/Huisgen 1,3-偶极环加成/叠氮化/点击反应。该策略似乎适合于从炔丙醇或烯丙醇/磺酰氯/肟/叠氮化钠/和末端炔烃开始以可持续的方式获得异恶唑/异恶唑啉连接的1,4-二取代1,2,3-三唑的新类似物。研究了超声波探头位置以及容器形状对化学反应的影响。本研究使用了三种不同类型的 25 mL 玻璃容器：圆底烧瓶、锥形烧瓶和梨形烧瓶。通过在 AgZr(PO) 材料上负载磁性 Fe3O 纳米粒子（FeO@AgZr(PO)）合成了异质纳米复合材料。使用各种技术（包括 FT-IR、EDX 和 XRD）对催化剂的结晶性质和纯度进行了表征。通过SEM分析表征分散性和形态。研究结果表明，尺寸为 50 至 75 nm 的 FeO 颗粒均匀分布在 AgZr(PO) 表面。水性反应
• Synthesis of new secretory phospholipase A2-inhibitory indole containing isoxazole derivatives as anti-inflammatory and anticancer agents
  作者：Srinivasa Rao Pedada、Nagendra Sastry Yarla、Pawan J. Tambade、Bhadrapura Lakkappa Dhananjaya、Anupam Bishayee、Kalle M. Arunasree、Gundala Harold Philip、Gangappa Dharmapuri、Gjumrach Aliev、Swathi Putta、Gururaja Rangaiah

  DOI：10.1016/j.ejmech.2016.02.025

  日期：2016.4

  Secretory phospholipase A(2) (sPLA(2)) is an important enzyme that plays a key role in various inflammatory diseases including cancer and its inhibitors have been developed as preventive or therapeutic agents. In the present study, a series of new indole containing isoxazole derivatives (10a-10o) is synthesized and evaluated for their sPLA(2) inhibitory activities. All compounds (10a-10o) showed significant sPLA(2) inhibition activities both in vitro and in vivo studies which is substantiated in in silico studies. Among all the tested compounds, 100 showed potent sPLA(2) inhibition activity, that is comparable or more to ursolic acid (positive control). Further studies demonstrated that 100 showed in vitro antiproliferative activity when tested against MCF-7 breast and DU145 prostate cancer cells. Furthermore, compounds 10a-10o obeyed lipinsky's rule of 5 and suggesting druggable properties. The in vitro, in vivo and in silico results are encouraging and warrant pre-clinical studies to develop sPLA(2)-inhibitory compound 10o as novel therapeutic agent for various inflammatory disorders and several malignancies. (C) 2016 Elsevier Masson SAS. All rights reserved.