5-methyl-4-phenyl-3-(2,4,6-trimethylphenyl)isoxazole | 374715-26-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 5-methyl-4-phenyl-3-(2,4,6-trimethylphenyl)isoxazole
• 英文别名: 3-mesityl-4-phenyl-5-methylisoxazole；5-methyl-4-phenyl-3-(2,4,6-trimethylphenyl)-1,2-oxazole
• CAS: 374715-26-1
• 化学式: C₁₉H₁₉NO
• 分子量: 277.366
• InChiKey: XEMGPWMXEPSKFU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  21
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  26
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  5-methyl-4-phenyl-3-(2,4,6-trimethylphenyl)isoxazole 在 氯磺酸 、 ammonium hydroxide 作用下， 反应 4.0h， 以44%的产率得到4-[5-methyl-3-(2,4,6-trimethylphenyl)-isoxazol-4-yl]-benzenesulfonamide
  参考文献：
  名称：

  Novel Synthesis of 3,4-Diarylisoxazole Analogues of Valdecoxib:  Reversal Cyclooxygenase-2 Selectivity by Sulfonamide Group Removal

  摘要：

  3,4-Diarylisoxazole analogues of valdecoxib [4-(5-methyl-3-phenylisoxazol-4-yl)-benzensulfonamide], a selective cyclooxygenase-2 (COX-2) inhibitor, were synthesized by 1,3-dipolar cycloaddition of arylnitrile oxides to the enolate ion of phenylacetone regioselectively prepared in situ with lithium diisopropylamide at 0 degreesC. The corresponding 3-aryl-5-methyl-4-phenylisoxazoles were easily generated by a dehydration/aromatization reaction under basic conditions of 3-aryl-5-hydroxy-5-methyl-4-phenyl-2-isoxazolines and further transformed into their benzenesulfonamide derivatives. The biochemical COX-1/COX-2 selectivity was evaluated in vitro by using the human whole blood assays of COX isozyme activity. Three compounds not bearing the sulfonamide group present in valdecoxib were selective COX-1 inhibitors.

  DOI：

  10.1021/jm040782x
• 作为产物：
  描述：

  2,4,6-三甲基苯甲腈N-氧化物 在 potassium phosphate 、 1,1'-双(二苯膦基)二茂铁二氯化钯(II)二氯甲烷复合物 作用下， 以 1,4-二氧六环 、 乙醚 为溶剂， 反应 128.0h， 生成 5-methyl-4-phenyl-3-(2,4,6-trimethylphenyl)isoxazole
  参考文献：
  名称：

  A regioselective cycloaddition route to isoxazoleboronic esters

  摘要：

  炔基硼酸盐能够参与与腈氧化物的1,3-偶极环加成反应，提供具有优异区域控制性的异恶唑硼酸酯；此外，这些被证明具有潜在价值的合成中间体还能高效参与铃木偶联反应。

  DOI：

  10.1039/b103319k

文献信息

• Use of isoxazole derivatives as cyclooxygenase inhibitors
  申请人：Universita' degli Studi di Bari

  公开号：EP2246337A1

  公开（公告）日：2010-11-03

  The present invention refers to the use of a compound selected from 3,4-diphenyl-5-ethylisoxazole and 3,4-diphenyl-5-methylisoxazole as inhibitors of cyclooxygenase, in particular of cyclooxygenase 1 and 2 (COX-1) (COX-2).

  本发明涉及一种选自 3,4-二苯基-5-乙基异噁唑和 3,4-二苯基-5-甲基异噁唑的化合物作为环氧化酶，特别是环氧化酶 1 和 2（COX-1）（COX-2）的抑制剂的用途。
• A regioselective cycloaddition route to isoxazoleboronic esters
  作者：Mark W. Davies、Robert A. J. Wybrow、Joseph P. A. Harrity、Christopher N. Johnson

  DOI：10.1039/b103319k

  日期：——

  Alkynylboronates participate in 1,3-dipolar cycloaddition reactions with nitrile oxides to provide isoxazoleboronic esters with excellent levels of regiocontrol; additionally, these potentially valuable synthetic intermediates have been shown to participate efficiently in Suzuki coupling reactions.

  炔基硼酸盐能够参与与腈氧化物的1,3-偶极环加成反应，提供具有优异区域控制性的异恶唑硼酸酯；此外，这些被证明具有潜在价值的合成中间体还能高效参与铃木偶联反应。
• Novel Synthesis of 3,4-Diarylisoxazole Analogues of Valdecoxib:  Reversal Cyclooxygenase-2 Selectivity by Sulfonamide Group Removal
  作者：Leonardo Di Nunno、Paola Vitale、Antonio Scilimati、Stefania Tacconelli、Paola Patrignani

  DOI：10.1021/jm040782x

  日期：2004.9.1

  3,4-Diarylisoxazole analogues of valdecoxib [4-(5-methyl-3-phenylisoxazol-4-yl)-benzensulfonamide], a selective cyclooxygenase-2 (COX-2) inhibitor, were synthesized by 1,3-dipolar cycloaddition of arylnitrile oxides to the enolate ion of phenylacetone regioselectively prepared in situ with lithium diisopropylamide at 0 degreesC. The corresponding 3-aryl-5-methyl-4-phenylisoxazoles were easily generated by a dehydration/aromatization reaction under basic conditions of 3-aryl-5-hydroxy-5-methyl-4-phenyl-2-isoxazolines and further transformed into their benzenesulfonamide derivatives. The biochemical COX-1/COX-2 selectivity was evaluated in vitro by using the human whole blood assays of COX isozyme activity. Three compounds not bearing the sulfonamide group present in valdecoxib were selective COX-1 inhibitors.