methyl 2,6-dimethyl-4-hydroxy-2H-1,2-benzothiazine-3-carboxylate-1,1-dioxide | 76780-06-8

• 分子结构分类: 有机化合物 - 有机杂环化合物
• 英文名称: methyl 2,6-dimethyl-4-hydroxy-2H-1,2-benzothiazine-3-carboxylate-1,1-dioxide
• 英文别名: methyl 4-hydroxy-2,6-dimethyl-2H-1,2-benzothiazine-3-carboxylate-1,1-dioxide；methyl 4-hydroxy-2,6-dimethyl-1,1-dioxo-1λ6,2-benzothiazine-3-carboxylate
• CAS: 76780-06-8
• 化学式: C₁₂H₁₃NO₅S
• 分子量: 283.305
• InChiKey: XWGVUWDMEPZVCF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  92.3
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  苯胺 、 methyl 2,6-dimethyl-4-hydroxy-2H-1,2-benzothiazine-3-carboxylate-1,1-dioxide 以 xylene 为溶剂， 反应 48.0h， 生成 4-Hydroxy-2,6-dimethyl-1,1-dioxo-1,2-dihydro-1λ⁶-benzo[e][1,2]thiazine-3-carboxylic acid phenylamide
  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：

  (5-Methyl-1,1,3-trioxo-1,3-dihydro-1λ⁶-benzo[d]isothiazol-2-yl)-acetic acid methyl ester 在 甲醇 、 sodium hydroxide 、 sodium methylate 作用下， 以 乙醇 、 甲苯 为溶剂， 反应 28.0h， 生成 methyl 2,6-dimethyl-4-hydroxy-2H-1,2-benzothiazine-3-carboxylate-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

• Antithrombotic
  申请人：Dr. Karl Thomae Gesellschaft mit beschrankter Haftung

  公开号：US04533664A1

  公开（公告）日：1985-08-06

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

  式为##STR1##的化合物，其中R.sub.1是氢、甲基、甲氧基、氟或氯；R.sub.2是氢、甲基、乙基或正丙基；以及与无机或有机碱形成的非毒性、药理学上可接受的盐。这些化合物以及盐可用作抗血栓药物。
• 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.

  该公式化合物的化学式为##STR1##其中R.sub.1是氢、甲基或乙基；R.sub.2是甲基、乙基或正丙基；Y是氢、甲基、甲氧基、氟或氯；以及与无机或有机碱形成的无毒、药理学上可接受的盐。这些化合物及其盐在抗炎方面有用。
• LOMBARDINO J. G., ORG. PREP. AND PROCED. INT., 1980, 12, NO 5, 269-274
  作者：LOMBARDINO J. G.

  DOI：——

  日期：——
• US4233299A
  申请人：——

  公开号：US4233299A

  公开（公告）日：1980-11-11
• US4533664A
  申请人：——

  公开号：US4533664A

  公开（公告）日：1985-08-06