2-ethyl-4-hydroxy-N-(5-methyl-2-thiazolyl)-2H-1,2-benzothiazine-3-carboxamide-1,1-dioxide

• 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: 2-ethyl-4-hydroxy-N-(5-methyl-2-thiazolyl)-2H-1,2-benzothiazine-3-carboxamide-1,1-dioxide
• 英文别名: 2-ethyl-4-hydroxy-N-(5-methyl-1,3-thiazol-2-yl)-1,1-dioxo-1λ6,2-benzothiazine-3-carboxamide
• 化学式: C₁₅H₁₅N₃O₄S₂
• 分子量: 365.434
• InChiKey: VVJVPQGBOPDBDS-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：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  136
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  4-羟基-2H-1,2-苯并噻嗪-3-羧酸甲酯1,1-二氧化物 在 sodium hydroxide 作用下， 以 乙醇 、 xylene 为溶剂， 反应 72.0h， 生成 2-ethyl-4-hydroxy-N-(5-methyl-2-thiazolyl)-2H-1,2-benzothiazine-3-carboxamide-1,1-dioxide
  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

• 4-Hydroxy-2H-1,2-benzothiazine-3-carboxamide-1,1-dioxides and salts
  申请人：Boehringer Ingelheim GmbH

  公开号：US04233299A1

  公开（公告）日：1980-11-11

  Compounds of the formula ##STR1## wherein R.sub.1 is hydrogen, methyl or ethyl; R.sub.2 is methyl, ethyl or n-propyl; and Y is hydrogen, methyl, methoxy, fluorine or chlorine; and non-toxic, pharmacologically acceptable salts thereof formed with an inorganic or organic base. The compounds as well as their salts are useful as antiphlogistics.

  式##STR1##中的化合物，其中R.sub.1为氢、甲基或乙基；R.sub.2为甲基、乙基或正丙基；Y为氢、甲基、甲氧基、氟或氯；以及与无机或有机碱形成的非毒性、药理学上可接受的盐。这些化合物及其盐可用作抗炎药。
• US4233299A
  申请人：——

  公开号：US4233299A

  公开（公告）日：1980-11-11
• US7432261B2
  申请人：——

  公开号：US7432261B2

  公开（公告）日：2008-10-07
• 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.