(9-amino-1,3,3-trioxo-1,2-dihydronaphtho[1,2-d]isothiazol-2-yl)acetic acid ethyl ester | 869541-24-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: (9-amino-1,3,3-trioxo-1,2-dihydronaphtho[1,2-d]isothiazol-2-yl)acetic acid ethyl ester
• 英文别名: Ethyl 2-(9-amino-1,3,3-trioxobenzo[e][1,2]benzothiazol-2-yl)acetate
• CAS: 869541-24-2
• 化学式: C₁₅H₁₄N₂O₅S
• 分子量: 334.353
• InChiKey: BMYZBZHGHGYXCR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  115
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (9-amino-1,3,3-trioxo-1,2-dihydronaphtho[1,2-d]isothiazol-2-yl)acetic acid ethyl ester 在 盐酸 作用下， 以72%的产率得到(9-Amino-1,3,3-trioxo-1,3-dihydro-3λ⁶-naphtho[1,2-d]isothiazol-2-yl)-acetic acid
  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 palladium on activated charcoal PPA 、 氢气 、 硝酸 、 sodium ethanolate 作用下， 以 乙醇 为溶剂， 反应 0.5h， 生成 (9-amino-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

文献信息

• Naphtho[1,2-<i>d</i>]isothiazole Acetic Acid Derivatives as a Novel Class of Selective Aldose Reductase Inhibitors
  作者：Federico Da Settimo、Giampaolo Primofiore、Concettina La Motta、Stefania Sartini、Sabrina Taliani、Francesca Simorini、Anna Maria Marini、Antonio Lavecchia、Ettore Novellino、Enrico Boldrini

  DOI：10.1021/jm050382p

  日期：2005.11.1

  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.