4-(1-Methylethyl)-2-<(phenylthio)methyl>-1,2-benzisothiazol-3(2H)-one 1,1-dioxide | 142601-62-5

• 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: 4-(1-Methylethyl)-2-<(phenylthio)methyl>-1,2-benzisothiazol-3(2H)-one 1,1-dioxide
• 英文别名: 2-Phenylthiomethyl-4-isopropylsaccharin；1,1-dioxo-2-(phenylsulfanylmethyl)-4-propan-2-yl-1,2-benzothiazol-3-one
• CAS: 142601-62-5
• 化学式: C₁₇H₁₇NO₃S₂
• 分子量: 347.459
• InChiKey: DDLHDRRADMRZTL-UHFFFAOYSA-N

物化性质

• 沸点：
  523.4±60.0 °C(Predicted)
• 密度：
  1.39±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  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：
  0.24
• 拓扑面积：
  88.1
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-(1-Methylethyl)-2-<(phenylthio)methyl>-1,2-benzisothiazol-3(2H)-one 1,1-dioxide 在 磺酰氯 作用下， 以 二氯甲烷 为溶剂， 以80%的产率得到2-(Chloromethyl)-4-(1-methylethyl)-1,2-benzisothiazol-3(2H)-one 1,1-dioxide
  参考文献：
  名称：

  Steric Effects on the Regioselectivity of an Azide-Alkyne Dipolar Cycloaddition Reaction: The Synthesis of Human Leukocyte Elastase Inhibitors

  摘要：

  The cycloaddition reaction of N-(azidomethyl)benzisothiazolone 4 with various electron-deficient acetylenes gave a novel series of 1,2,3-triazoles 5-15 that were prepared for testing as inhibitors of human leukocyte elastase (HLE). Steric effects controlled the reaction regioselectivity, since as the acetylene substituent size increased from hydrogen to phenyl, tert-butyl, and trimethylsilyl, the regioisomer ratios reversed. An electronic effect of silicon appears to be responsible for the formation of only one isomer with the trimethylsilyl acetylenecarboxylate and ethynyl sulfone. For example, the 5-(phenylsulfonyl)triazole 13b was the only regioisomer detected in the reaction of phenyl 2-(trimethylsilyl)ethynyl sulfone with the azide 4. The strongly electron-withdrawing sulfone exerted no control over the regioselectivity of the cycloaddition reaction in comparison to the dominating effect of the trimethylsilyl group. High pressure and water as solvent were separately shown to accelerate the rate of product formation. The structures were unambiguously assigned on the basis of an X-ray crystal structure determination and NOE difference experiments. The derivative 12a, WIN 68123, is a potent HLE inhibitor with an apparent binding constant (K-i*) of 0.38 nM.

  DOI：

  10.1021/jo00100a019
• 作为产物：
  描述：

  氯甲基苯硫醚 、 4-(1-Methylethyl)-1,2-benzisothiazol-3(2H)-one 1,1-dioxide 在 四丁基溴化铵 作用下， 以 甲苯 为溶剂， 反应 24.0h， 以92%的产率得到4-(1-Methylethyl)-2-<(phenylthio)methyl>-1,2-benzisothiazol-3(2H)-one 1,1-dioxide
  参考文献：
  名称：

  Steric Effects on the Regioselectivity of an Azide-Alkyne Dipolar Cycloaddition Reaction: The Synthesis of Human Leukocyte Elastase Inhibitors

  摘要：

  The cycloaddition reaction of N-(azidomethyl)benzisothiazolone 4 with various electron-deficient acetylenes gave a novel series of 1,2,3-triazoles 5-15 that were prepared for testing as inhibitors of human leukocyte elastase (HLE). Steric effects controlled the reaction regioselectivity, since as the acetylene substituent size increased from hydrogen to phenyl, tert-butyl, and trimethylsilyl, the regioisomer ratios reversed. An electronic effect of silicon appears to be responsible for the formation of only one isomer with the trimethylsilyl acetylenecarboxylate and ethynyl sulfone. For example, the 5-(phenylsulfonyl)triazole 13b was the only regioisomer detected in the reaction of phenyl 2-(trimethylsilyl)ethynyl sulfone with the azide 4. The strongly electron-withdrawing sulfone exerted no control over the regioselectivity of the cycloaddition reaction in comparison to the dominating effect of the trimethylsilyl group. High pressure and water as solvent were separately shown to accelerate the rate of product formation. The structures were unambiguously assigned on the basis of an X-ray crystal structure determination and NOE difference experiments. The derivative 12a, WIN 68123, is a potent HLE inhibitor with an apparent binding constant (K-i*) of 0.38 nM.

  DOI：

  10.1021/jo00100a019

文献信息

• Saccharin derivative proteolytic enzyme inhibitors
  申请人：Sterling Winthrop Inc.

  公开号：US05378720A1

  公开（公告）日：1995-01-03

  Compounds having the structural formula ##STR1## which inhibit the enzymatic activity of proteolytic enzymes, and processes for preparation thereof, method of use thereof in treatment of degenerative diseases and pharmaceutical compositions thereof are disclosed.

  本发明揭示了具有结构式##STR1##的化合物，其抑制蛋白酶酶活性，以及其制备方法，治疗退行性疾病的使用方法和制药组合物。
• US5378720A
  申请人：——

  公开号：US5378720A

  公开（公告）日：1995-01-03
• US5466701A
  申请人：——

  公开号：US5466701A

  公开（公告）日：1995-11-14
• Steric Effects on the Regioselectivity of an Azide-Alkyne Dipolar Cycloaddition Reaction: The Synthesis of Human Leukocyte Elastase Inhibitors
  作者：Dennis J. Hlasta、James H. Ackerman

  DOI：10.1021/jo00100a019

  日期：1994.10

  The cycloaddition reaction of N-(azidomethyl)benzisothiazolone 4 with various electron-deficient acetylenes gave a novel series of 1,2,3-triazoles 5-15 that were prepared for testing as inhibitors of human leukocyte elastase (HLE). Steric effects controlled the reaction regioselectivity, since as the acetylene substituent size increased from hydrogen to phenyl, tert-butyl, and trimethylsilyl, the regioisomer ratios reversed. An electronic effect of silicon appears to be responsible for the formation of only one isomer with the trimethylsilyl acetylenecarboxylate and ethynyl sulfone. For example, the 5-(phenylsulfonyl)triazole 13b was the only regioisomer detected in the reaction of phenyl 2-(trimethylsilyl)ethynyl sulfone with the azide 4. The strongly electron-withdrawing sulfone exerted no control over the regioselectivity of the cycloaddition reaction in comparison to the dominating effect of the trimethylsilyl group. High pressure and water as solvent were separately shown to accelerate the rate of product formation. The structures were unambiguously assigned on the basis of an X-ray crystal structure determination and NOE difference experiments. The derivative 12a, WIN 68123, is a potent HLE inhibitor with an apparent binding constant (K-i*) of 0.38 nM.