6-chloro-N-(2-chlorophenyl)-3-hydroxy-2-methyl-1,1-dioxo-1lambda6,2-benzothiazine-4-carboxamide | 188423-04-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并噻嗪类
• 英文名称: 6-chloro-N-(2-chlorophenyl)-3-hydroxy-2-methyl-1,1-dioxo-1lambda6,2-benzothiazine-4-carboxamide
• 英文别名: 6-chloro-N-(2-chlorophenyl)-3-hydroxy-2-methyl-1,1-dioxo-1λ6,2-benzothiazine-4-carboxamide
• CAS: 188423-04-3
• 化学式: C₁₆H₁₂Cl₂N₂O₄S
• 分子量: 399.254
• InChiKey: ZMIZKLFUKIHSJC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  25
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  95.1
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  6-chloro-N-(2-chlorophenyl)-3-hydroxy-2-methyl-1,1-dioxo-1lambda6,2-benzothiazine-4-carboxamide 以 甲苯 为溶剂， 反应 2.0h， 生成 6-chloro-N-(2,4-dibromophenyl)-3-hydroxy-2-methyl-1,1-dioxo-1lambda6,2-benzothiazine-4-carboxamide
  参考文献：
  名称：

  Effect of Structural Modification of Enol−Carboxamide-Type Nonsteroidal Antiinflammatory Drugs on COX-2/COX-1 Selectivity

  摘要：

  Meloxicam (5), an NSAID in the enol-carboxamide class, was developed on the basis of its antiinflammatory activity and relative safety in animal models. In subsequent screening in microsomal assays using human COX-1 and COX-2, we discovered that it possessed a selectivity profile for COX-2 superior to piroxicam and other marketed NSAIDs. We therefore embarked on a study of enol-carboxamide type compounds to determine if COX-2 selectivity and potency could be dramatically improved by structural modification. Substitution at the 6- and 7-positions of the 4-oxo-1,2-benzothiazine-3-carboxamide, alteration of the N-methyl substituent, and amide modification were all examined. In addition we explored several related systems including the isomeric 3-oxo-1,2-benzothiazine-4-carboxamides, thienothiazines, indolothiazines, benzothienothiazines, naphthothiazines, and 1,3- and 1,4-dioxoisoquinolines. While a few examples were found with greater potency in the COX-2 assay, no compound tested had a better COX-2/COX-1 selectivity profile than that of 5.

  DOI：

  10.1021/jm9607010
• 作为产物：
  描述：

  1,2,4-三氯萘 、 6-chloro-2-methyl-1,1-dioxo-4H-1lambda6,2-benzothiazin-3-one 在 三乙胺 作用下， 以 二甲基亚砜 为溶剂， 反应 2.0h， 生成 6-chloro-N-(2-chlorophenyl)-3-hydroxy-2-methyl-1,1-dioxo-1lambda6,2-benzothiazine-4-carboxamide
  参考文献：
  名称：

  Effect of Structural Modification of Enol−Carboxamide-Type Nonsteroidal Antiinflammatory Drugs on COX-2/COX-1 Selectivity

  摘要：

  Meloxicam (5), an NSAID in the enol-carboxamide class, was developed on the basis of its antiinflammatory activity and relative safety in animal models. In subsequent screening in microsomal assays using human COX-1 and COX-2, we discovered that it possessed a selectivity profile for COX-2 superior to piroxicam and other marketed NSAIDs. We therefore embarked on a study of enol-carboxamide type compounds to determine if COX-2 selectivity and potency could be dramatically improved by structural modification. Substitution at the 6- and 7-positions of the 4-oxo-1,2-benzothiazine-3-carboxamide, alteration of the N-methyl substituent, and amide modification were all examined. In addition we explored several related systems including the isomeric 3-oxo-1,2-benzothiazine-4-carboxamides, thienothiazines, indolothiazines, benzothienothiazines, naphthothiazines, and 1,3- and 1,4-dioxoisoquinolines. While a few examples were found with greater potency in the COX-2 assay, no compound tested had a better COX-2/COX-1 selectivity profile than that of 5.

  DOI：

  10.1021/jm9607010