3,4-dihydro-2,6-dimethyl-3-oxo-2H-thieno[2,3-e]-1,2-thiazine 1,1-dioxide | 869734-05-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻吩并噻嗪类
• 英文名称: 3,4-dihydro-2,6-dimethyl-3-oxo-2H-thieno[2,3-e]-1,2-thiazine 1,1-dioxide
• 英文别名: 2,6-dimethyl-1,1-dioxo-4H-thieno[2,3-e]thiazin-3-one
• CAS: 869734-05-4
• 化学式: C₈H₉NO₃S₂
• 分子量: 231.296
• InChiKey: ABUGJFKEPKIPBK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  14
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  91.1
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-异氰酸酯吡啶 、 3,4-dihydro-2,6-dimethyl-3-oxo-2H-thieno[2,3-e]-1,2-thiazine 1,1-dioxide 在 三乙胺 作用下， 以 二甲基亚砜 为溶剂， 反应 1.0h， 生成 3-hydroxy-2,6-dimethyl-1,1-dioxo-N-pyridin-2-ylthieno[2,3-e]thiazine-4-carboxamide
  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：

  2-氯-5-甲基噻吩 在 甲醇 、 氯磺酸 、 正丁基锂 、 氯化亚砜 、 三乙胺 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 7.0h， 生成 3,4-dihydro-2,6-dimethyl-3-oxo-2H-thieno[2,3-e]-1,2-thiazine 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

• Method of treating diseases and conditions associated with an altered level of amyloid beta peptides and new enolcarboxamide compounds
  申请人：Bornemann Klaus

  公开号：US20050277635A1

  公开（公告）日：2005-12-15

  A method of treating or preventing of a disease or condition associated with an increased level of isoforms of amyloid β peptides (Aβ) and/or with a changed ratio of levels of Aβ isoforms and/or with the formation of plaques containing amyloid β peptide (Aβ) isoforms in a mammal comprising administering to said mammal an therapeutically effective amount of a compound selected from the formulas Ia, Ib wherein V, W, Y, R 2 , R 3 , R 5 , R 6 , L1 and i are defined as in claim 1.

  一种治疗或预防与哺乳动物中淀粉样β肽（Aβ）异构体水平增加、Aβ异构体水平比例改变和/或含有Aβ肽的斑块形成有关的疾病或病症的方法，包括向该哺乳动物投与公式Ia、Ib中选定的化合物的治疗有效量，其中V、W、Y、R2、R3、R5、R6、L1和i的定义如权利要求1所述。
• Method of Treating Diseases and Conditions Associated with an Altered Level of Amyloid Beta Peptides and New Enolcarboxamide Compounds
  申请人：BORNEMANN Klaus

  公开号：US20090099159A1

  公开（公告）日：2009-04-16

  A method of treating or preventing of a disease or condition associated with an increased level of isoforms of amyloid β peptides (Aβ) and/or with a changed ratio of levels of Aβ isoforms and/or with the formation of plaques containing amyloid β peptide (Aβ) isoforms in a mammal comprising administering to said mammal an therapeutically effective amount of a compound selected from the formulas Ia, Ib wherein V, W, Y, R 2 , R 3 , R 5 , R 6 , L 1 and i are defined as in claim 1.

  一种治疗或预防与哺乳动物中淀粉样β肽（Aβ）的同工异构体水平增加和/或Aβ同工异构体水平比例改变和/或含有Aβ同工异构体的斑块形成相关的疾病或病症的方法，包括向该哺乳动物施用从Ia、Ib公式中选择的化合物的治疗有效量，其中V、W、Y、R2、R3、R5、R6、L1和i如权利要求1中所定义。
• Method of treating diseases and conditions associated with an altered level of amyloid β peptides and new enolcarboxamide compounds
  申请人：Boehringer Ingelheim International GmbH

  公开号：US07393843B2

  公开（公告）日：2008-07-01

  A method of treating or preventing of a disease or condition associated with an increased level of isoforms of amyloid β peptides (Aβ) and/or with a changed ratio of levels of Aβ isoforms and/or with the formation of plaques containing amyloid β peptide (Aβ) isoforms in a mammal comprising administering to said mammal an therapeutically effective amount of a compound selected from the formulas Ia, Ib wherein V, W, Y, R2, R3, R5, R6, L1 and i are defined as in claim 1.

  一种治疗或预防与哺乳动物中淀粉样β肽（Aβ）的异构体水平增高以及/或Aβ异构体水平比例改变和/或形成含有Aβ肽（Aβ）异构体的斑块相关的疾病或病症的方法，包括向该哺乳动物投与一种从公式Ia，Ib中选择的化合物的治疗有效量，其中V、W、Y、R2、R3、R5、R6、L1和i的定义如权利要求1所述。
• Method of treating diseases and conditions associated with an altered level of amyloid β peptides and new enolcarboxamide compounds
  申请人：Boehringer Ingelheim Vetmedica GmbH

  公开号：US07375220B2

  公开（公告）日：2008-05-20

  A method of treating or preventing of a disease or condition associated with an increased level of isoforms of amyloid β peptides (Aβ) and/or with a changed ratio of levels of Aβ isoforms and/or with the formation of plaques containing amyloid β peptide (Aβ) isoforms in a mammal comprising administering to said mammal an therapeutically effective amount of a compound selected from the formulas Ia, Ib wherein V, W, Y, R2, R3, R5, R6, L1 and i are defined as in claim 1.

  一种治疗或预防与哺乳动物中淀粉样β肽（Aβ）的异构体水平增加以及/或Aβ异构体水平比例改变和/或形成含有Aβ肽（Aβ）异构体的斑块相关的疾病或症状的方法，包括向该哺乳动物施用公式Ia、Ib中选择的化合物的治疗有效量，其中V、W、Y、R2、R3、R5、R6、L1和i如权利要求1所定义。
• [EN] TREATMENT OF DISEASES ASSOCIATED WITH ALTERED LEVEL OF AMYLOID BETA PEPTIDES<br/>[FR] PROCEDE POUR TRAITER DES MALADIES ET DES ETATS ASSOCIES A UN NIVEAU MODIFIE DE PEPTIDES BETA AMYLOIDES ET NOUVEAUX COMPOSES D'ENOLCARBOXAMIDE
  申请人：BOEHRINGER INGELHEIM INT

  公开号：WO2005110422A3

  公开（公告）日：2006-05-18