methyl 6-chloro-4-hydroxy-1,1-dioxo-1,2-dihydro-1H,1H -1λ⁶,2-benzothiazine-3-carboxylate | 188422-57-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并噻唑类
• 英文名称: methyl 6-chloro-4-hydroxy-1,1-dioxo-1,2-dihydro-1H,1H -1λ⁶,2-benzothiazine-3-carboxylate
• 英文别名: methyl 6-chloro-4-hydroxy-2H-1,2-benzothiazine-3-carboxylate-1,1-dioxide；methyl 6-chloro-4-hydroxy-1,1-dioxo-2H-1λ6,2-benzothiazine-3-carboxylate
• CAS: 188422-57-3
• 化学式: C₁₀H₈ClNO₅S
• 分子量: 289.696
• InChiKey: KOVTYULYRFRDTH-UHFFFAOYSA-N

物化性质

• 沸点：
  473.0±55.0 °C(Predicted)
• 密度：
  1.658±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  101
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  methyl 6-chloro-4-hydroxy-1,1-dioxo-1,2-dihydro-1H,1H -1λ⁶,2-benzothiazine-3-carboxylate 在 sodium hydroxide 作用下， 以 乙醇 、 xylene 为溶剂， 反应 72.0h， 生成 6-Chloro-4-hydroxy-2-methyl-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
• 作为产物：
  描述：

  (5-Chloro-1,1,3-trioxo-1,3-dihydro-1λ⁶-benzo[d]isothiazol-2-yl)-acetic acid methyl ester 在 sodium methylate 作用下， 以 甲醇 为溶剂， 以49 %的产率得到methyl 6-chloro-4-hydroxy-1,1-dioxo-1,2-dihydro-1H,1H -1λ⁶,2-benzothiazine-3-carboxylate
  参考文献：
  名称：

  N-杂环卡宾有机催化[3+3]环化反应选择性合成苯并吡喃噻嗪酮

  摘要：

  该设计受奥昔康核心结构的启发，允许采用 N-杂环卡宾 (NHC) 催化对映选择性合成苯并吡喃噻嗪酮基序。 NHC 介导的转化涉及 α,β-不饱和醛与合适的取代苯并噻嗪酮衍生物的反应。该过程包括从炔醛初始形成 α,β-不饱和酰唑鎓，同时从苯并噻嗪酮生成烯醇化物。这些反应的最终结果是有效的环化，产生具有合理产率和高立体选择性的所需产物。这项研究强调了 NHC 催化在简化复杂杂环结构合成中的潜力。

  DOI：

  10.1002/adsc.202301082

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。
• Endothelin receptor antagonists: synthesis and structure–activity relationships of substituted benzothiazine-1,1-dioxides
  作者：K.A. Berryman、J.J. Edmunds、A.M. Bunker、S. Haleen、J. Bryant、K.M. Welch、A.M. Doherty

  DOI：10.1016/s0968-0896(98)00080-7

  日期：1998.9

  The development of benzothiazine-1,1-dioxide derivatives as a new structural class of potent endothelin receptor antagonists is described. Structure-activity relationships (SAR) revealed that PD164800 (1) is a potent antagonist of the ETA receptor subtype. (C) 1998 Elsevier Science Ltd. All rights reserved.
• US4233299A
  申请人：——

  公开号：US4233299A

  公开（公告）日：1980-11-11