7-methoxy-4-methyl-1,1-dioxo-1,4-dihydro-2H-1λ⁶-isothiazolo[4,5-b]indol-3-one | 67929-91-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 7-methoxy-4-methyl-1,1-dioxo-1,4-dihydro-2H-1λ⁶-isothiazolo[4,5-b]indol-3-one
• 英文别名: 7-methoxy-4-methyl-2H-isothiazolo[4,5-b]indole-3(4H)-one-1,1-dioxide；7-methoxy-4-methyl-1,1-dioxo-[1,2]thiazolo[4,5-b]indol-3-one
• CAS: 67929-91-3
• 化学式: C₁₁H₁₀N₂O₄S
• 分子量: 266.277
• InChiKey: AYMDUZFNXSFXJS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  18
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  85.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  7-methoxy-4-methyl-1,1-dioxo-1,4-dihydro-2H-1λ⁶-isothiazolo[4,5-b]indol-3-one 在 甲醇 、 sodium hydroxide 、 sodium methylate 、 sodium hydride 作用下， 以 乙醇 、 甲苯 为溶剂， 反应 32.5h， 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
• 作为产物：
  描述：

  5-Methoxy-1-methyl-3-sulfinamoyl-1H-indole-2-carboxylic acid methyl ester 、 potassium permanganate 以 丙酮 、 水 为溶剂， 以33.7 gm (78% of theory) of methyl 5-methoxy-1-methyl-3-sulfamoyl-indole-2-carboxylate, M.p.: 190° C., and 7.4 gm (19% of theory) of 7-methoxy-4-methyl-2H-isothiazolo[4,5-b]indole-3(4H)-one-1,1-dioxide, M.p.: above 290° C. (decomposition), were obtained的产率得到methyl 5-methoxy-1-methyl-3-sulfamoyl-indole-2-carboxylate
  参考文献：
  名称：

  2,5-Dihydro-1,2-thiazino(5,6-b)indole-3-carboxamide-1,1-dioxides and

  摘要：

  该化合物的分子式为##STR1## 其中R.sub.1为氢、甲基或乙基；R.sub.2为甲基或乙基；Y为氢、氟、氯、溴、甲氧基、甲基、乙基或三氟甲基；Ar为2-噻唑基，可以有一个或两个甲基或乙基取代基；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，可以有一个甲基取代基；2-吡啶基，可以有一个甲基或羟基取代基；3-吡啶基；4-吡啶基；4-嘧啶基；吡嗪基；2-苯并咪唑基；2-噁唑基，可以有一个甲基取代基；2-苯并噁唑基；或苯基，可以有氟、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无毒、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。

  公开号：

  US04137313A1

文献信息

• US4137313A
  申请人：——

  公开号：US4137313A

  公开（公告）日：1979-01-30
• 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.
• 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.

  该化合物的分子式为##STR1## 其中R.sub.1为氢、甲基或乙基；R.sub.2为甲基或乙基；Y为氢、氟、氯、溴、甲氧基、甲基、乙基或三氟甲基；Ar为2-噻唑基，可以有一个或两个甲基或乙基取代基；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，可以有一个甲基取代基；2-吡啶基，可以有一个甲基或羟基取代基；3-吡啶基；4-吡啶基；4-嘧啶基；吡嗪基；2-苯并咪唑基；2-噁唑基，可以有一个甲基取代基；2-苯并噁唑基；或苯基，可以有氟、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无毒、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。