4-cyclopropylmethoxy-3-methoxy-2-chloromethyl pyridine hydrochloride

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 4-cyclopropylmethoxy-3-methoxy-2-chloromethyl pyridine hydrochloride
• 英文别名: 2-(chloromethyl)-4-(cyclopropylmethoxy)-3-methoxypyridine;hydrochloride
• 化学式: C₁₁H₁₄ClNO₂*ClH
• 分子量: 264.152
• InChiKey: QQUWFYMMMHZAED-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.04
• 重原子数：
  16
• 可旋转键数：
  5
• 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：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-cyclopropylmethoxy-3-methoxy-2-chloromethyl pyridine hydrochloride 在 sodium hydroxide 、 碳酸氢钠 、 间氯过氧苯甲酸 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 0.17h， 生成 2-(4-Cyclopropylmethoxy-3-methoxy-pyridin-2-ylmethanesulfinyl)-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 hydroxide 、 氯化亚砜 、 sodium hydride 、 potassium carbonate 、 间氯过氧苯甲酸 、 三氯氧磷 作用下， 以 二氯甲烷 、 丙酮 为溶剂， 反应 64.0h， 生成 4-cyclopropylmethoxy-3-methoxy-2-chloromethyl pyridine hydrochloride
  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

• Dialkoxy-pyridinyl-benzimidazole derivatives, process for their
  申请人：Aktiebolaget Astra

  公开号：US05430042A1

  公开（公告）日：1995-07-04

  The novel compounds of the formula I ##STR1## and physiologically acceptable salts thereof, wherein R.sup.1 and R.sup.2, which are different is each H alkyl containing 1-4 carbon atoms or --C(O)--R.sup.5 ; wherein R.sup.5 is alkyl containing 1-4 carbon atoms or alkoxy containing 1-4 carbon atoms and one of R.sup.1, or R.sup.2 is always selected from the group --C(O)--R.sup.5 ; R.sup.3 and R.sup.4 are the same or different and selected from ##STR2## and --CH.sub.2 CH.sub.2 OCH.sub.3 or R.sup.3 and R.sup.4 together with the adjacent oxygen atoms atached to the pyridine ring and the carbon atoms in the pyridine ring form a ring, wherein the part constituted by R.sup.3 and R.sup.4 is --CH.sub.2 CH.sub.2 CH.sub.2 --, or --CH.sub.2 --CH.sub.2 -- or --CH.sub.2 --; as well as intermediates, pharmaceutical compositions containing such compounds as active ingredient and the use of the compounds in medicine.

  该式的新化合物及其生理上可接受的盐，其中R.sup.1和R.sup.2是不同的，分别是含有1-4个碳原子的H烷基或--C(O)--R.sup.5；其中R.sup.5是含有1-4个碳原子的烷基或含有1-4个碳原子的烷氧基，R.sup.1或R.sup.2中的一个始终选择自群--C(O)--R.sup.5；R.sup.3和R.sup.4相同或不同，选择自##STR2## 和--CH.sub.2 CH.sub.2 OCH.sub.3，或者R.sup.3和R.sup.4与连接到吡啶环上的相邻氧原子和吡啶环中的碳原子一起形成一个环，其中由R.sup.3和R.sup.4构成的部分为--CH.sub.2 CH.sub.2 CH.sub.2--，或--CH.sub.2--CH.sub.2--或--CH.sub.2--；以及中间体、含有这种化合物作为活性成分的药物组合物和在医学中使用这种化合物。
• DIALKOXY-PYRIDINYL-BENZIMIDAZOLE DERIVATIVES, PROCESS FOR THEIR PREPARATION AND THEIR PHARMACEUTICAL USE
  申请人：AKTIEBOLAGET ASTRA

  公开号：EP0593463A1

  公开（公告）日：1994-04-27
• US5430042A
  申请人：——

  公开号：US5430042A

  公开（公告）日：1995-07-04
• [EN] DIALKOXY-PYRIDINYL-BENZIMIDAZOLE DERIVATIVES, PROCESS FOR THEIR PREPARATION AND THEIR PHARMACEUTICAL USE
  申请人：——

  公开号：WO1991019712A1

  公开（公告）日：1991-12-26

  [EN] The novel compounds of formula (I) and physiologically acceptable salts thereof, wherein R<1> and R<2>, which are different, is each H, alkyl containing 1-4 carbon atoms or -C(O)-R<5>; wherein R<5> is alkyl containing 1-4 carbon atoms or alkoxy containing 1-4 carbon atoms and one of R<1>, or R<2> is always selected from the group -C(O)-R<5>; R<3> and R<4> are the same or different and selected from -CH3, -C2H5, (a), (b), and -CH2CH2OCH3 or R<3> and R<4> together with the adjacent oxygen atoms attached to the pyridine ring and the carbon atoms in the pyridine ring form a ring, wherein the part constituted by R<3> and R<4> is -CH2CH2CH2-, or -CH2-CH2- or -CH2-; as well as intermediates, pharmaceutical compositions containing such compounds as active ingredient and use of the compounds in medicine.
  [FR] On décrit de nouveaux composés de formule (I) et des sels physiologiquement acceptables de ceux-ci, où R1 et R2, qui sont différents, représentent chacun H, un alkyle contenant de 1 à 4 atomes de carbone ou -C(O)-R5; où R5 représente un alkyle contenant de 1 à 4 atomes de carbone ou un alcoxy contenant de 1 à 4 atomes de carbone et soit R1 soit R2 est toujours choisi à partir du groupe -C(O)-R5; R3 et R4 sont les mêmes ou différents et choisis à partir de -CH3, -C2H5, (a), (b), et -CH2CH2OCH3, ou R3 et R4 forment un cycle avec les atomes d'oxygène contigus rattachés au cycle pyridique et les atomes de carbone dans le cycle pyridique, où la partie composée de R3 et R4 représente -CH2CH2CH2-, ou -CH2-CH2- ou -CH2-. On décrit aussi des éléments intermédiaires, des compositions pharmaceutiques contenant de tels composés comme ingrédient actif et l'utilisation de ces composés dans le domaine médical.
• 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.