methyl 2-(5-methoxy-1,1,3-trioxo-1,3-dihydro-2H-1,2-benzisothiazol-2-yl)acetate | 182163-01-5

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: methyl 2-(5-methoxy-1,1,3-trioxo-1,3-dihydro-2H-1,2-benzisothiazol-2-yl)acetate
• 英文别名: (5-Methoxy-1,1,3-trioxo-1,3-dihydro-1λ6-benzo[d]isothiazol-2-yl)-acetic acid methyl ester；Methyl 2-(5-methoxy-1,1,3-trioxo-1,2-benzothiazol-2-yl)acetate
• CAS: 182163-01-5
• 化学式: C₁₁H₁₁NO₆S
• 分子量: 285.277
• InChiKey: ZGTICBGNGSRUEU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  98.4
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  methyl 2-(5-methoxy-1,1,3-trioxo-1,3-dihydro-2H-1,2-benzisothiazol-2-yl)acetate 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 4-hydroxy-6-methoxy-2-methyl-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
• 作为产物：
  描述：

  在 chromium(VI) oxide 、 乙酸酐 、 过碘酸 作用下， 以 乙腈 为溶剂， 以17%的产率得到methyl 2-(5-methoxy-1,1,3-trioxo-1,3-dihydro-2H-1,2-benzisothiazol-2-yl)acetate
  参考文献：
  名称：

  氨基酸的糖精衍生物的制备作为潜在的拟肽构建块

  摘要：

  摘要 我们提出了一种制备氨基酸糖精衍生物的有用途径。合成了 16 种新化合物，即糖精衍生的氨基酸，它们都在糖精骨架的 5 位或 6 位带有额外的官能团，从而使这些化合物更易于官能化。

  DOI：

  10.1080/00397910802149105

文献信息

• [EN] BENZOTHIAZINE DIOXIDES AS ENDOTHELIN ANTAGONISTS<br/>[FR] DIOXYDES DE BENZOTHIAZINE UTILISES COMME ANTAGONISTES DE L'ENDOTHELINE
  申请人：WARNER-LAMBERT COMPANY

  公开号：WO1996026195A1

  公开（公告）日：1996-08-29

  (EN) Novel benzothiazine dioxides which are antagonists of endothelin are described, as well as novel intermediates used in their preparation, methods for the preparation, and pharmaceutical compositions of the same, which are useful in treating elevated levels of endohelin, essential renovascular malignant and pulmonary hypertension, cerebral infarction, cerebral ischemia, congestive heart failure, and subarachnoid hemorrhage.(FR) La présente invention concerne de nouveaux dioxydes de benzothiazine qui sont des antagonistes de l'endothéline, ainsi que de nouveaux intermédiaires utilisés pour leur préparation, des procédés de préparation et des compositions pharmaceutiques à base de ces nouveaux dioxydes de benzothiazine. Ces nouveaux dioxydes de benzothiazine sont utiles dans le traitement des niveaux élevés d'endothéline, de l'hypertension artérielle rénovasculaire et pulmonaire essentielle maligne, de l'infarctus cérébral, de l'insuffisance cardiaque congestive et de l'hémorragie sous-arachnoïdienne.

  描述了一种新的苯并噻唑二氧化物，它们是内皮素拮抗剂，以及用于它们的制备的新中间体，制备方法和相应的药物组成物，这些药物组成物在治疗内皮素水平升高、重要肾血管恶性和肺动脉高压、脑梗死、脑缺血、充血性心力衰竭和蛛网膜下腔出血方面有用。
• 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.
• BENZOTHIAZINE DIOXIDES AS ENDOTHELIN ANTAGONISTS
  申请人：WARNER-LAMBERT COMPANY

  公开号：EP0811001B1

  公开（公告）日：2001-10-31
• 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.
• Preparation of Saccharin Derivatives of Amino Acids as Potential Peptidomimetic Building Blocks
  作者：Žiga Jakopin、Marija Sollner Dolenc

  DOI：10.1080/00397910802149105

  日期：2008.9.29

  Abstract We present a useful route for the preparation of saccharin derivatives of amino acids. Sixteen new compounds, saccharin-derived amino acids, were synthesized, all of them bearing additional functional groups either at the 5- or 6-position of the saccharin skeleton, thus rendering the compounds more amenable to functionalization.

  摘要 我们提出了一种制备氨基酸糖精衍生物的有用途径。合成了 16 种新化合物，即糖精衍生的氨基酸，它们都在糖精骨架的 5 位或 6 位带有额外的官能团，从而使这些化合物更易于官能化。