4-环丙基甲氧基-3-甲氧基-2-甲基-吡啶 | 1026940-59-9

• 分子结构分类: 有机化合物 - 有机氧化合物
• 中文名称: 4-环丙基甲氧基-3-甲氧基-2-甲基-吡啶
• 英文名称: 4-(Cyclopropylmethoxy)-3-methoxy-2-methylpyridine
• CAS: 1026940-59-9
• 化学式: C₁₁H₁₅NO₂
• 分子量: 193.246
• InChiKey: WQYRKHIWWLUQPE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  14
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  31.4
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-环丙基甲氧基-3-甲氧基-2-甲基-吡啶 在 sodium hydroxide 、 氯化亚砜 、 间氯过氧苯甲酸 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 22.0h， 生成 2-(4-Cyclopropylmethoxy-3-methoxy-pyridin-2-ylmethylsulfanyl)-5-fluoro-1H-benzoimidazole
  参考文献：
  名称：

  Structure-Activity Relationship of Omeprazole and Analogs as Helicobacter pylori Urease Inhibitors

  摘要：

  Helicobacter pylori urease belongs to a family of highly conserved urea-hydrolyzing enzymes. A common feature of these enzymes is the presence of two Lewis acid nickel ions and a reactive cysteine residue in the active site. The H+/K(+)-ATPase inhibitor omeprazole is a prodrug of a sulfenamide which covalently modifies cysteine residues on the luminal side of the H+/K(+)-ATPase of gastric parietal cells. Omeprazole and eight analogues were selected based on their chemical, electronic, and kinetic properties, and each was incubated with viable H. pylori in phosphate-buffered saline at pH 7.4 for 30 min, after which 100 mM urea was added and the amount of ammonia formed analyzed after a further 10 min. Inhibition between 0% and 100% at a 0.1 mM concentration was observed for the different analogues and could be expressed as a function of the pKa-value of the pyridine, the pKa-value of the benzimidazole, the overall lipophilicity, and, most importantly, the rate of sulfenamide formation, in a quantitative structure-activity relationship. The inhibition was potentiated by a lower pH (favoring the formation of the sulfenamide) but abolished in the presence of beta-mercaptoethanol (a scavenger of the sulfenamide). Structural analogues incapable of yielding the sulfenamide did not inhibit ammonia production. Treatment of Helicobacter felis-infected mice with 230 mumol/kg flurofamide b.i.d. for 4 weeks, known to potently inhibit urease activity in vivo, as a means of eradicating the infection, was tested and compared with the effect of 125 mumol/kg omeprazole b.i.d. for 4 weeks. Neither treatment proved efficacious.

  DOI：

  10.1021/jm00025a008
• 作为产物：
  描述：

  麦芽醇 在 ammonium hydroxide 、 sodium hydride 、 potassium carbonate 、 三氯氧磷 作用下， 以 丙酮 为溶剂， 反应 42.0h， 生成 4-环丙基甲氧基-3-甲氧基-2-甲基-吡啶
  参考文献：
  名称：

  Structure-Activity Relationship of Omeprazole and Analogs as Helicobacter pylori Urease Inhibitors

  摘要：

  Helicobacter pylori urease belongs to a family of highly conserved urea-hydrolyzing enzymes. A common feature of these enzymes is the presence of two Lewis acid nickel ions and a reactive cysteine residue in the active site. The H+/K(+)-ATPase inhibitor omeprazole is a prodrug of a sulfenamide which covalently modifies cysteine residues on the luminal side of the H+/K(+)-ATPase of gastric parietal cells. Omeprazole and eight analogues were selected based on their chemical, electronic, and kinetic properties, and each was incubated with viable H. pylori in phosphate-buffered saline at pH 7.4 for 30 min, after which 100 mM urea was added and the amount of ammonia formed analyzed after a further 10 min. Inhibition between 0% and 100% at a 0.1 mM concentration was observed for the different analogues and could be expressed as a function of the pKa-value of the pyridine, the pKa-value of the benzimidazole, the overall lipophilicity, and, most importantly, the rate of sulfenamide formation, in a quantitative structure-activity relationship. The inhibition was potentiated by a lower pH (favoring the formation of the sulfenamide) but abolished in the presence of beta-mercaptoethanol (a scavenger of the sulfenamide). Structural analogues incapable of yielding the sulfenamide did not inhibit ammonia production. Treatment of Helicobacter felis-infected mice with 230 mumol/kg flurofamide b.i.d. for 4 weeks, known to potently inhibit urease activity in vivo, as a means of eradicating the infection, was tested and compared with the effect of 125 mumol/kg omeprazole b.i.d. for 4 weeks. Neither treatment proved efficacious.

  DOI：

  10.1021/jm00025a008

文献信息

• Structure-Activity Relationship of Omeprazole and Analogs as Helicobacter pylori Urease Inhibitors
  作者：Thomas C. Kuehler、Jan Fryklund、Nils-ke Bergman、Jessica Weilitz、Adrian Lee、Haakan Larsson

  DOI：10.1021/jm00025a008

  日期：1995.12

  Helicobacter pylori urease belongs to a family of highly conserved urea-hydrolyzing enzymes. A common feature of these enzymes is the presence of two Lewis acid nickel ions and a reactive cysteine residue in the active site. The H+/K(+)-ATPase inhibitor omeprazole is a prodrug of a sulfenamide which covalently modifies cysteine residues on the luminal side of the H+/K(+)-ATPase of gastric parietal cells. Omeprazole and eight analogues were selected based on their chemical, electronic, and kinetic properties, and each was incubated with viable H. pylori in phosphate-buffered saline at pH 7.4 for 30 min, after which 100 mM urea was added and the amount of ammonia formed analyzed after a further 10 min. Inhibition between 0% and 100% at a 0.1 mM concentration was observed for the different analogues and could be expressed as a function of the pKa-value of the pyridine, the pKa-value of the benzimidazole, the overall lipophilicity, and, most importantly, the rate of sulfenamide formation, in a quantitative structure-activity relationship. The inhibition was potentiated by a lower pH (favoring the formation of the sulfenamide) but abolished in the presence of beta-mercaptoethanol (a scavenger of the sulfenamide). Structural analogues incapable of yielding the sulfenamide did not inhibit ammonia production. Treatment of Helicobacter felis-infected mice with 230 mumol/kg flurofamide b.i.d. for 4 weeks, known to potently inhibit urease activity in vivo, as a means of eradicating the infection, was tested and compared with the effect of 125 mumol/kg omeprazole b.i.d. for 4 weeks. Neither treatment proved efficacious.