8-methoxy-2,5-dimethyl-1,1,4-trioxo-2,3,4,5-tetrahydro-1H-[1,2]thiazino[5,6-b]indole-3-carboxylic acid methyl ester | 67929-94-6

• 分子结构分类: 有机化合物 - 有机杂环化合物
• 英文名称: 8-methoxy-2,5-dimethyl-1,1,4-trioxo-2,3,4,5-tetrahydro-1H-[1,2]thiazino[5,6-b]indole-3-carboxylic acid methyl ester
• 英文别名: methyl 2,5-dihydro-2,5-dimethyl-4-hydroxy-8-methoxy-1,2-thiazino[5,6-b]indole-3-carboxylate 1,1-dioxide；methyl 4-hydroxy-8-methoxy-2,5-dimethyl-1,1-dioxothiazino[5,6-b]indole-3-carboxylate
• CAS: 67929-94-6
• 化学式: C₁₅H₁₆N₂O₆S
• 分子量: 352.368
• InChiKey: MBRARZSDFFOZSZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  24
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  106
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  8-methoxy-2,5-dimethyl-1,1,4-trioxo-2,3,4,5-tetrahydro-1H-[1,2]thiazino[5,6-b]indole-3-carboxylic acid methyl ester 、 2-氨基噻唑 以 xylene 为溶剂， 反应 48.0h， 生成 8-methoxy-2,5-dimethyl-1,1,4-trioxo-2,3,4,5-tetrahydro-1H-[1,2]thiazino[5,6-b]indole-3-carboxylic acid thiazol-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
• 作为产物：
  描述：

  (7-methoxy-4-methyl-1,1-dioxo-3,4-dihydro-1H-1λ⁶-isothiazolo[4,5-b]indol-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 8-methoxy-2,5-dimethyl-1,1,4-trioxo-2,3,4,5-tetrahydro-1H-[1,2]thiazino[5,6-b]indole-3-carboxylic acid methyl ester
  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

• 2,5-Dihydro-1,2-thiazino(5,6-b)indole-3-carboxamide-1,1-dioxides and
  申请人：Boehringer Ingelheim GmbH

  公开号：US04137313A1

  公开（公告）日：1979-01-30

  Compounds of the formula ##STR1## WHEREIN R.sub.1 is hydrogen, methyl or ethyl; R.sub.2 is methyl or ethyl; Y is hydrogen, fluorine, chlorine, bromine, methoxy, methyl, ethyl or trifluoromethyl; and Ar is 2-thiazolyl which may have one or two methyl or ethyl substituents attached thereto; 5,6-dihydro-4H-cyclopentathiazol-2-yl; 4,5,6,7-tetrahydro-2-benzothiazolyl; 2-benzothiazolyl; 3-isothiazolyl which may have a methyl substituent attached thereto; 2-pyridyl which may have a methyl or hydroxyl substituent attached thereto; 3-pyridyl; 4-pyridyl; 4-pyrimidinyl; pyrazinyl; 2-benzimidazolyl; 2-oxazolyl which may have a methyl substituent attached thereto; 2-benzoxazolyl; or phenyl which may have a fluoro, chloro, bromo, methyl, ethyl, trifluoromethyl or methoxy substituent attached thereto; and non-toxic, pharmacologically acceptable salts thereof formed with inorganic or organic bases. The compounds as well as their salts are useful as antiphlogistics and blood platelet aggregation inhibitors.

  式为 ##STR1## 的化合物，其中 R.sub.1 是氢、甲基或乙基；R.sub.2 是甲基或乙基；Y 是氢、氟、氯、溴、甲氧基、甲基、乙基或三氟甲基；Ar 是2-噻唑基，可能具有一个或两个连接的甲基或乙基取代基；5,6-二氢-4H-环戊噻唑-2-基；4,5,6,7-四氢-2-苯并噻唑基；2-苯并噻唑基；3-异噻唑基，可能具有一个连接的甲基取代基；2-吡啶基，可能具有一个连接的甲基或羟基取代基；3-吡啶基；4-吡啶基；4-吡咪啶基；吡嗪基；2-苯并咪唑基；2-噁唑基，可能具有一个连接的甲基取代基；2-苯并噁唑基；或苯基，可能具有一个氟、氯、溴、甲基、乙基、三氟甲基或甲氧基取代基；以及与无机或有机碱形成的非毒性、药理学上可接受的盐。这些化合物及其盐可用作抗炎药和血小板聚集抑制剂。
• US4137313A
  申请人：——

  公开号：US4137313A

  公开（公告）日：1979-01-30