{4-[3-(tert-Butoxycarbonylamino-methyl)-4-(2-methoxy-ethoxymethoxy)-phenylsulfanyl]-2,3-dichloro-phenoxy}-acetic acid ethyl ester | 93134-87-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: {4-[3-(tert-Butoxycarbonylamino-methyl)-4-(2-methoxy-ethoxymethoxy)-phenylsulfanyl]-2,3-dichloro-phenoxy}-acetic acid ethyl ester
• CAS: 93134-87-3
• 化学式: C₂₆H₃₃Cl₂NO₈S
• 分子量: 590.522
• InChiKey: VUUJEISESQDLMG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.11
• 重原子数：
  38.0
• 可旋转键数：
  14.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  101.55
• 氢给体数：
  1.0
• 氢受体数：
  9.0

反应信息

• 作为反应物：
  描述：

  {4-[3-(tert-Butoxycarbonylamino-methyl)-4-(2-methoxy-ethoxymethoxy)-phenylsulfanyl]-2,3-dichloro-phenoxy}-acetic acid ethyl ester 在 吡啶 、 2,3-二氯碘苯 、 水 作用下， 以1.46 g的产率得到{4-[3-(tert-Butoxycarbonylamino-methyl)-4-(2-methoxy-ethoxymethoxy)-benzenesulfinyl]-2,3-dichloro-phenoxy}-acetic acid ethyl ester
  参考文献：
  名称：

  [(Aminomethyl)aryloxy]acetic acid esters. A new class of high-ceiling diuretics. 3. Variation in the bridge between the aromatic rings to complete mapping of the receptor

  摘要：

  Continued structural evaluation of the [(aminomethyl)aryloxy]acetic ester diuretics has produced a series of compounds in which the functional group that bridges the two aromatic rings has been varied. Diuretic screening of these analogues in rats indicates that the keto group can be effectively replaced with an ether or thio ether function with a slight increase in potency, whereas the methylene and sulfoxide linking groups lead to diminished saluretic potency. Replacement with either -SO2-, -COCO-, -CH2O-, -CONH- or direct bond results in a loss of activity. Although the series was designed according to QSAR criteria, the traditional linear free-energy properties of these compounds do not correlate with diuretic potency. However, conformational analysis of the series by potential energy calculations indicates that all active compounds have an accessible conformation that matches the bridge atom-carboxylate distance of the very potent dihydrobenzofuran analogue 56. Conformational calculations of several compounds in which the aminomethyl group was varied suggests that the active conformation is probably a low-energy conformation. Consideration of rotation about the bridge could not distinguish between two possible orientations of the aminomethyl ring in the active conformation. However, there is a quantitative negative linear correlation between diuretic potency and the protrusion into space of the group that bridges the two aromatic rings.

  DOI：

  10.1021/jm00379a016
• 作为产物：
  描述：

  对氟硝基苯 在 sulfided Pt/C 盐酸 、 三氯化铝 、 硫酸 、 氢气 、 potassium carbonate 、 sodium sulfate 、 三乙胺 、 N,N-二异丙基乙胺 、 sodium nitrite 作用下， 以 乙醇 、 二氯甲烷 、 溶剂黄146 、 N,N-二甲基甲酰胺 、 丁酮 为溶剂， 反应 14.0h， 生成 {4-[3-(tert-Butoxycarbonylamino-methyl)-4-(2-methoxy-ethoxymethoxy)-phenylsulfanyl]-2,3-dichloro-phenoxy}-acetic acid ethyl ester
  参考文献：
  名称：

  [(Aminomethyl)aryloxy]acetic acid esters. A new class of high-ceiling diuretics. 3. Variation in the bridge between the aromatic rings to complete mapping of the receptor

  摘要：

  Continued structural evaluation of the [(aminomethyl)aryloxy]acetic ester diuretics has produced a series of compounds in which the functional group that bridges the two aromatic rings has been varied. Diuretic screening of these analogues in rats indicates that the keto group can be effectively replaced with an ether or thio ether function with a slight increase in potency, whereas the methylene and sulfoxide linking groups lead to diminished saluretic potency. Replacement with either -SO2-, -COCO-, -CH2O-, -CONH- or direct bond results in a loss of activity. Although the series was designed according to QSAR criteria, the traditional linear free-energy properties of these compounds do not correlate with diuretic potency. However, conformational analysis of the series by potential energy calculations indicates that all active compounds have an accessible conformation that matches the bridge atom-carboxylate distance of the very potent dihydrobenzofuran analogue 56. Conformational calculations of several compounds in which the aminomethyl group was varied suggests that the active conformation is probably a low-energy conformation. Consideration of rotation about the bridge could not distinguish between two possible orientations of the aminomethyl ring in the active conformation. However, there is a quantitative negative linear correlation between diuretic potency and the protrusion into space of the group that bridges the two aromatic rings.

  DOI：

  10.1021/jm00379a016