N-tert-butyl-4-[2-methyl-4-(5-methylthien-2-yl)-oxazol-5-yl]benzenesulfonamide | 415679-07-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: N-tert-butyl-4-[2-methyl-4-(5-methylthien-2-yl)-oxazol-5-yl]benzenesulfonamide
• 英文别名: N-tert-butyl-4-[2-methyl-4-(5-methylthiophen-2-yl)-1,3-oxazol-5-yl]benzenesulfonamide
• CAS: 415679-07-1
• 化学式: C₁₉H₂₂N₂O₃S₂
• 分子量: 390.527
• InChiKey: ADNLJADDOGWUTL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  26
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  109
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  N-tert-butyl-4-[2-methyl-4-(5-methylthien-2-yl)-oxazol-5-yl]benzenesulfonamide 在 三氟乙酸 作用下， 以85%的产率得到4-[2-Methyl-4-(5-methyl-thiophen-2-yl)-oxazol-5-yl]-benzenesulfonamide
  参考文献：
  名称：

  4-(4-Cycloalkyl/aryl-oxazol-5-yl)benzenesulfonamides as Selective Cyclooxygenase-2 Inhibitors:  Enhancement of the Selectivity by Introduction of a Fluorine Atom and Identification of a Potent, Highly Selective, and Orally Active COX-2 Inhibitor JTE-522

  摘要：

  A series of 4-(4-cycloalkyl/aryl-oxazol-5-yl)benzenesulfonamide derivatives were synthesized and evaluated for their abilities to inhibit cyclooxygenase-2 (COX-2) and cyclooxygenase-1 (COX-1) enzymes. In this series, substituent effects at the ortho position to the sulfonamide group on the phenyl ring were examined. Most substituents reduced or lost both COX-2 and COX-1 activities. In contrast, introduction of a fluorine atom preserved COX-2 potency and notably increased COX-1/COX-2 selectivity. This work led to the identification of a potent, highly selective, and orally active COX-2 inhibitor JTE-522 [9d, 4-(4-cyclohexyl-2-methyloxazol-5-yl)2-fluorobenzenesulfonamide], which is currently in phase II clinical trials for the treatment of rheumatoid arthritis, osteoarthritis, and acute pain.

  DOI：

  10.1021/jm010484p
• 作为产物：
  描述：

  5-甲基噻吩-2-羰酰氯 在 四(三苯基膦)钯 、 ammonium acetate 、 溶剂黄146 、 锌 作用下， 以 乙二醇二甲醚 为溶剂， 反应 4.0h， 生成 N-tert-butyl-4-[2-methyl-4-(5-methylthien-2-yl)-oxazol-5-yl]benzenesulfonamide
  参考文献：
  名称：

  4-(4-Cycloalkyl/aryl-oxazol-5-yl)benzenesulfonamides as Selective Cyclooxygenase-2 Inhibitors:  Enhancement of the Selectivity by Introduction of a Fluorine Atom and Identification of a Potent, Highly Selective, and Orally Active COX-2 Inhibitor JTE-522

  摘要：

  A series of 4-(4-cycloalkyl/aryl-oxazol-5-yl)benzenesulfonamide derivatives were synthesized and evaluated for their abilities to inhibit cyclooxygenase-2 (COX-2) and cyclooxygenase-1 (COX-1) enzymes. In this series, substituent effects at the ortho position to the sulfonamide group on the phenyl ring were examined. Most substituents reduced or lost both COX-2 and COX-1 activities. In contrast, introduction of a fluorine atom preserved COX-2 potency and notably increased COX-1/COX-2 selectivity. This work led to the identification of a potent, highly selective, and orally active COX-2 inhibitor JTE-522 [9d, 4-(4-cyclohexyl-2-methyloxazol-5-yl)2-fluorobenzenesulfonamide], which is currently in phase II clinical trials for the treatment of rheumatoid arthritis, osteoarthritis, and acute pain.

  DOI：

  10.1021/jm010484p