5-(3-hydroxy-4-methoxyphenyl)-4-(4-methoxyphenyl)isoxazole | 1271728-01-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 酚类
• 英文名称: 5-(3-hydroxy-4-methoxyphenyl)-4-(4-methoxyphenyl)isoxazole
• 英文别名: 2-Methoxy-5-[4-(4-methoxyphenyl)-5-isoxazolyl]phenol；2-methoxy-5-[4-(4-methoxyphenyl)-1,2-oxazol-5-yl]phenol
• CAS: 1271728-01-8
• 化学式: C₁₇H₁₅NO₄
• mdl: MFCD32223271
• 分子量: 297.31
• InChiKey: JTQKACYQFFRVPN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  64.7
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  (5-乙酰基-2-甲氧基苯基)乙酸酯 在 吡啶 、 碘苯二乙酸 、 硫酸 、 盐酸羟胺 、 sodium hydroxide 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 29.0h， 生成 5-(3-hydroxy-4-methoxyphenyl)-4-(4-methoxyphenyl)isoxazole
  参考文献：
  名称：

  A convenient synthesis of cis-restricted combretastatin analogues with pyrazole and isoxazole cores

  摘要：

  A series of combretastatin analogues, diarylpyrazoles and diarylisoxazoles, have been synthesized and evaluated for their antimitotic tubulin-binding activity using the phenotypic sea urchin (Paracentrotus lividus) embryo assay. One pyrazole analogue and four isoxazole analogues have been identified as potent antimitotic agents comparable with combretastatins A-2 and A-4, with the lowest observable effective concentration of 1-10 nmol dm(-3) for cleavage alteration of the test embryos.

  DOI：

  10.1016/j.mencom.2019.03.015

文献信息

• Sea Urchin Embryo Model As a Reliable in Vivo Phenotypic Screen to Characterize Selective Antimitotic Molecules. Comparative evaluation of Combretapyrazoles, -isoxazoles, -1,2,3-triazoles, and -pyrroles as Tubulin-Binding Agents
  作者：Marina N. Semenova、Dmitry V. Demchuk、Dmitry V. Tsyganov、Natalia B. Chernysheva、Alexander V. Samet、Eugenia A. Silyanova、Victor P. Kislyi、Anna S. Maksimenko、Alexander E. Varakutin、Leonid D. Konyushkin、Mikhail M. Raihstat、Alex S. Kiselyov、Victor V. Semenov

  DOI：10.1021/acscombsci.8b00113

  日期：2018.12.10

  antitubulin activity using in vivo sea urchin embryo assay and a panel of human cancer cells. A systematic comparative structure–activity relationship studies of these compounds were conducted. Pyrazoles 1i and 1p, isoxazole 3a, and triazole 7b were found to be the most potent antimitotics across all tested compounds causing cleavage alteration of the sea urchin embryo at 1, 0.25, 1, and 0.5 nM, respectively

  通过改进的方案合成了一系列新颖的和已报道的康布雷他汀类似物，包括二芳基吡唑，-异恶唑，-1,2,3-三唑和-吡咯，以使用体内海胆胚胎测定法和专家小组评估其抗有丝分裂的抗微管蛋白活性。人类癌细胞 对这些化合物进行了系统的比较结构-活性关系研究。吡唑1i和1p，异恶唑3a和三唑7b被发现是所有测试化合物中最有效的抗有丝分裂剂，分别导致海胆胚胎的裂解改变分别为1、0.25、1和0.5 nM。这些试剂对人癌细胞显示出可比的细胞毒性。结构-活性关系研究表明，被3,4,5-三甲氧基苯基环A和4-甲氧基苯基环B取代的化合物表现出最高的活性。B环中的3-羟基对于二芳基异恶唑系列的抗增殖活性至关重要，而对二芳基吡唑的效力则不是必需的。具有3,4,5-三甲氧基取代的环A和3-羟基-4-甲氧基取代的环B的异恶唑3比各自的吡唑1具有更高的活性。与同一组的其他芳药效团取代的唑类，二芳基的1，4,5- diarylisoxazoles
• Biological evaluation of KRIBB3 analogs as a microtubule polymerization inhibitor
  作者：Sangku Lee、Jae Nyoung Kim、Hyeong Kyu Lee、Kab Seog Yoon、Ki Deok Shin、Byoung-Mog Kwon、Dong Cho Han

  DOI：10.1016/j.bmcl.2010.12.044

  日期：2011.2

  A series of KRIBB3 analogs were synthesized by modifying substituents at aryl moieties of KRIBB3 for examining structure-activity relationships, and their inhibitory activities on microtubule polymerization were evaluated. The presence of free phenolic hydrogens in aryl moieties of KRIBB3 analogs plays an important role in inhibition of microtubule polymerization. (C) 2010 Elsevier Ltd. All rights reserved.
• A convenient synthesis of cis-restricted combretastatin analogues with pyrazole and isoxazole cores
  作者：Dmitry V. Tsyganov、Marina N. Semenova、Leonid D. Konyushkin、Vladimir I. Ushkarov、Mikhail M. Raihstat、Victor V. Semenov

  DOI：10.1016/j.mencom.2019.03.015

  日期：2019.3

  A series of combretastatin analogues, diarylpyrazoles and diarylisoxazoles, have been synthesized and evaluated for their antimitotic tubulin-binding activity using the phenotypic sea urchin (Paracentrotus lividus) embryo assay. One pyrazole analogue and four isoxazole analogues have been identified as potent antimitotic agents comparable with combretastatins A-2 and A-4, with the lowest observable effective concentration of 1-10 nmol dm(-3) for cleavage alteration of the test embryos.