4-Hydroxy-2,6-dimethyl-1,1-dioxo-1,2-dihydro-1λ⁶-benzo[e][1,2]thiazine-3-carboxylic acid pyridin-2-ylamide

• 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: 4-Hydroxy-2,6-dimethyl-1,1-dioxo-1,2-dihydro-1λ⁶-benzo[e][1,2]thiazine-3-carboxylic acid pyridin-2-ylamide
• 英文别名: 4-hydroxy-2,6-dimethyl-1,1-dioxo-N-pyridin-2-yl-1lambda6,2-benzothiazine-3-carboxamide；4-hydroxy-2,6-dimethyl-1,1-dioxo-N-pyridin-2-yl-1λ6,2-benzothiazine-3-carboxamide
• 化学式: C₁₆H₁₅N₃O₄S
• 分子量: 345.379
• InChiKey: AXIKERUEVQMHGZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  24
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  108
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  5-methyl-1,1-dioxo-1,2-benzothiazol-3-one 在 甲醇 、 sodium hydroxide 、 sodium methylate 、 sodium hydride 作用下， 以 乙醇 、 甲苯 、 xylene 为溶剂， 反应 80.5h， 生成 4-Hydroxy-2,6-dimethyl-1,1-dioxo-1,2-dihydro-1λ⁶-benzo[e][1,2]thiazine-3-carboxylic acid pyridin-2-ylamide
  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

文献信息

• LOMBARDINO J. G., ORG. PREP. AND PROCED. INT., 1980, 12, NO 5, 269-274
  作者：LOMBARDINO J. G.

  DOI：——

  日期：——
• Effect of Structural Modification of Enol−Carboxamide-Type Nonsteroidal Antiinflammatory Drugs on COX-2/COX-1 Selectivity
  作者：Edward S. Lazer、Clara K. Miao、Charles L. Cywin、Ronald Sorcek、Hin-Chor Wong、Zhaoxing Meng、Ian Potocki、MaryAnn Hoermann、Roger J. Snow、Matt A. Tschantz、Terence A. Kelly、Daniel W. McNeil、Simon J. Coutts、Laurie Churchill、Anne G. Graham、Eva David、Peter M. Grob、Wolfhard Engel、Hans Meier、Günter Trummlitz

  DOI：10.1021/jm9607010

  日期：1997.3.1

  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.