2,3-Dihydronaphth[1,2-d]isothiazol-1(2H)-one 3,3-dioxide | 29083-19-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 2,3-Dihydronaphth[1,2-d]isothiazol-1(2H)-one 3,3-dioxide
• 英文别名: 3,3-dioxidenaphtho[1,2-d]isothiazole-1(2H)-one；3,3-dioxo-2,3-dihydro-3λ⁶-naphtho[1,2-d]isothiazol-1-one；3,3-dioxo-3λ⁶-naphth[1,2-d]isothiazol-1-one；3,3-Dioxo-3λ⁶-naphth[1,2-d]isothiazol-1-on；3,3-Dioxobenzo[e][1,2]benzothiazol-1-one
• CAS: 29083-19-0
• 化学式: C₁₁H₇NO₃S
• 分子量: 233.247
• InChiKey: KKKOEFHLFPCEPS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  16
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  71.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2,3-Dihydronaphth[1,2-d]isothiazol-1(2H)-one 3,3-dioxide 在 硝酸 、 sodium ethanolate 作用下， 以 乙醇 为溶剂， 反应 0.25h， 生成 (6-nitro-1,3,3-trioxo-1,2-dihydronaphtho[1,2-d]isothiazol-2-yl)acetic acid ethyl ester
  参考文献：
  名称：

  Naphtho[1,2-d]isothiazole Acetic Acid Derivatives as a Novel Class of Selective Aldose Reductase Inhibitors

  摘要：

  Acetic acid derivatives of naphtho[1,2-dlisothiazole (NiT) were synthesized and tested as novel aldose reductase (ALR2) inhibitors. The parent compound 11 exhibited a fair inhibitory activity (IC50 = 10 mu M), which was enhanced by 2 orders of magnitude by introducing a second carboxylic group at position 4 (13 and 14: IC50 = 0.55 and 0.14 mu M, respectively). Substitution of the acetic acid function with an apolar group gave inactive (29) or poorly active (25, 26, 30) compounds, thus demonstrating that the 2-acetic group is involved in the enzyme pharmacophoric recognition while the 4-carboxylic moiety has only an accessory role. The potent compounds 11, 13, 14, 26 all proved to be selective for ALR2, since none of them inhibited aldehyde reductase, sorbitol dehydrogenase, or glutathione reductase. The isopropyl. ester 31, a prodrug of 14, was found to be effective in preventing cataract development in severely galactosemic rats, when administered as an eyedrop solution. The theoretical binding mode of 13 and 14, obtained by docking simulations into the ALR2 crystal structure, was fully consistent with the structure-activity relationships in the NiT series.

  DOI：

  10.1021/jm050382p
• 作为产物：
  描述：

  2-tert-butylsulfamoylnaphthalene-1-carboxylic acid 在 PPA 作用下， 反应 0.25h， 以30%的产率得到2,3-Dihydronaphth[1,2-d]isothiazol-1(2H)-one 3,3-dioxide
  参考文献：
  名称：

  Naphtho[1,2-d]isothiazole Acetic Acid Derivatives as a Novel Class of Selective Aldose Reductase Inhibitors

  摘要：

  Acetic acid derivatives of naphtho[1,2-dlisothiazole (NiT) were synthesized and tested as novel aldose reductase (ALR2) inhibitors. The parent compound 11 exhibited a fair inhibitory activity (IC50 = 10 mu M), which was enhanced by 2 orders of magnitude by introducing a second carboxylic group at position 4 (13 and 14: IC50 = 0.55 and 0.14 mu M, respectively). Substitution of the acetic acid function with an apolar group gave inactive (29) or poorly active (25, 26, 30) compounds, thus demonstrating that the 2-acetic group is involved in the enzyme pharmacophoric recognition while the 4-carboxylic moiety has only an accessory role. The potent compounds 11, 13, 14, 26 all proved to be selective for ALR2, since none of them inhibited aldehyde reductase, sorbitol dehydrogenase, or glutathione reductase. The isopropyl. ester 31, a prodrug of 14, was found to be effective in preventing cataract development in severely galactosemic rats, when administered as an eyedrop solution. The theoretical binding mode of 13 and 14, obtained by docking simulations into the ALR2 crystal structure, was fully consistent with the structure-activity relationships in the NiT series.

  DOI：

  10.1021/jm050382p

文献信息

• 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.
• Synthesis and activity of 2-(sulfonamido)methyl-carbapenems: Discovery of a novel, anti-MRSA 1,8-naphthosultam pharmacophore
  作者：R.R. Wilkening、R.W. Ratcliffe、K.J. Wildonger、L.D. Cama、K.D. Dykstra、F.P. DiNinno、T.A. Blizzard、M.L. Hammond、J.V. Heck、K.L. Dorso、E.St. Rose、J. Kohler、G.G. Hammond

  DOI：10.1016/s0960-894x(99)00070-0

  日期：1999.3

  A series of 1 beta-methyl carbapenems substituted at the IL-position with lipophilic, acyclic and cyclic (sulfonamido)methyl groups was prepared and evaluated for activity against resistant gram-positive bacteria. From these studies, the 1,8-naphthosultamyl group emerged as a novel, PBP2a-binding, anti-MRSA pharmacophore worthy of further exploration. (C) 1999 Elsevier Science Ltd. All rights reserved.
• Preparation of substituted 1,2-benzoisothiazolin-3-one 1,1-dioxides (o-benzoic sulfimides)
  作者：Joseph G. Lombardino

  DOI：10.1021/jo00812a032

  日期：1971.7
• Doepp, Dietrich; Lauterfeld, Peter; Schneider, Markus, Synthesis, 2001, # 8, p. 1228 - 1235
  作者：Doepp, Dietrich、Lauterfeld, Peter、Schneider, Markus、Schneider, Dietmar、Henkel, Gerald、Issac, Yvette Abd el Sayed、Elghamry, Ibrahim

  DOI：——

  日期：——
• Kalcher, Justus Liebigs Annalen der Chemie, 1918, vol. 414, p. 245
  作者：Kalcher

  DOI：——

  日期：——