5-hydroxy-5-methyl-3,4-diphenyl-2-isoxazoline

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 二苯乙烯类
• 英文名称: 5-hydroxy-5-methyl-3,4-diphenyl-2-isoxazoline
• 英文别名: (4S,5S)-5-methyl-3,4-diphenyl-4H-1,2-oxazol-5-ol
• 化学式: C₁₆H₁₅NO₂
• 分子量: 253.301
• InChiKey: LOFHVOCXHGAVHL-HOCLYGCPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  41.8
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  苯甲腈 N-氧化物 、 苯基丙酮 在 正丁基锂 、 二异丙胺 作用下， 以 四氢呋喃 、 正己烷 为溶剂， 反应 1.0h， 生成 5-hydroxy-5-methyl-3,4-diphenyl-2-isoxazoline 、 5-hydroxy-5-methyl-3,4-diphenyl-2-isoxazoline
  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

文献信息

• 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.