N¹-methyl rabeprazole

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并咪唑类
• 英文名称: N¹-methyl rabeprazole
• 英文别名: 2-{4-(3-Methoxypropoxy)-3-methylpyridine-2-yl}methylsulfinyl-1-methylbenzimidazole；2-[[4-(3-methoxypropoxy)-3-methylpyridin-2-yl]methylsulfinyl]-1-methylbenzimidazole
• 化学式: C₁₉H₂₃N₃O₃S
• 分子量: 373.476
• InChiKey: SQWIPZCPIAPXNP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  26
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  85.4
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  2-{4-(3-methoxypropoxy)-3-methylpyridine-2-yl}methylthio-1-methylbenzimidazole 在 碳酸氢钠 、 三乙胺 、 间氯过氧苯甲酸 作用下， 以 二氯甲烷 为溶剂， 生成 N¹-methyl rabeprazole
  参考文献：
  名称：

  Pyridine derivatives having anti-ulcerative activity

  摘要：

  可用于预防或治疗消化性溃疡的吡啶衍生物、药物制剂及治疗消化性溃疡的方法。

  公开号：

  US05045552A1

文献信息

• Chemistry of Covalent Inhibition of the Gastric (H⁺, K⁺)-ATPase by Proton Pump Inhibitors
  作者：Jai Moo Shin、Young Moon Cho、George Sachs

  DOI：10.1021/ja049607w

  日期：2004.6.1

  either substituted pyridylmethylsulfinyl benzimidazole or imidazopyridine derivatives. They are all prodrugs that inhibit the acid-secreting gastric (H(+), K(+))-ATPase by acid activation to reactive thiophiles that form disulfide bonds with one or more cysteines accessible from the exoplasmic surface of the enzyme. This unique acid-catalysis mechanism had been ascribed to the nucleophilicity of the

  质子泵抑制剂 (PPI) 是广泛用于治疗酸相关疾病的药物，是取代的吡啶基甲基亚磺酰基苯并咪唑或咪唑并吡啶衍生物。它们都是通过酸激活反应性亲硫体来抑制胃分泌酸 (H(+), K(+))-ATPase 的前药，这些亲硫体与一个或多个可从酶的外质表面接触的半胱氨酸形成二硫键。这种独特的酸催化机制归因于吡啶环的亲核性。然而，此处获得的数据表明，它们向反应性阳离子亲硫磺酸或次磺酰胺的转化主要不依赖于吡啶质子化，而是依赖于咪唑组分的第二次质子化，这增加了咪唑上 C-2 位的亲电性。这种质子化导致 C-2 与吡啶环的未质子化部分反应形成反应性衍生物。相关的 PPI pK(a) 由苯并咪唑或咪唑并吡啶亚磺酰基甲基部分在不同介质 pH 值下的紫外光谱测定。相对酸稳定的类似物 N(1)-甲基兰索拉唑 (6b) 的合成允许直接测定该完整 PPI 的两个 pK(a) 值，从而可以计算所有 PPI 的两个 pK(a)
• Pyridine derivatives, pharmaceutical compositions comprising the same, the use of the same for the manufacture of medicaments having therapeutic or preventative value, and a process for preparing the same
  申请人：Eisai Co., Ltd.

  公开号：EP0786461A1

  公开（公告）日：1997-07-30

  The invention provides pyridine derivatives represented by the general formula: wherein R1 and R2 may be the same or different from each other and each stand for a hydrogen atom, a C1-6 alkyl, C1-6 alkoxy, halogenated C1-6 alkyl, (C1-6 alkoxy) carbonyl or carboxyl group or a halogen atom; X stands for a group represented by the formula: -O-, -S-or (wherein R3 stands for a hydrogen atom or a C1-6 alkyl, phenyl, benzyl or (C1-6 alkoxy)carbonyl group); Z stands for ① a group represented by the general formula:         -0-(CH2)q-R5 wherein q stands for an integer of 1 to 3 and R5 stands for a halogen atom or an (C1-6 alkoxy) carbonyl, aryl or heteroaryl group, ② a group represented by the general formula:         -0-(CH2)r-0-(CH2)s-0-R6 wherein r and s each stand for an integer of 1 to 5 and R6 stands for a hydrogen atom or a C1-6 alkyl group, ③ a group represented by the formula: ④ a group represented by the general formula: wherein t stands for an integer of 0 to 2 and A stands for a group represented by the general formula: (wherein B stands for a group represented by the formula: -NH-, -0- or -S-), a C1-6 aklyl, (C1-6 alkoxy)carbonylmethyl, pyridyl or furyl group or a group represented by the general formula: (wherein R7 stands for a hydrogen atom, a C1-6 alkyl or C1-6 alkoxy group or a halogen atom and w stands for an integer of 0 or 1), ⑤ a group represented by the general formula: wherein R8 stands for an acetoxy or C1-6 alkyl group, n stands for an integer of 0 to 2, m stands for an integer of 2 to 10, and J and K may be the same or different from each other and each stand for a hydrogen atom or a C1-6 alkyl group, and a pharmaceutically acceptable salt thereof. Pharmaceutical compositions comprising these derivatives are also provided, together with the use of the derivatives for the manufacture of medicaments having therapeutic or preventative value in the treatment of peptic ulcers. Processes for preparing such pyridine derivatives are also provided.

  本发明提供了由一般式表示的吡啶衍生物：其中R1和R2可以相同或不同，分别代表氢原子，C1-6烷基，C1-6烷氧基，卤代C1-6烷基，(C1-6烷氧基)羰基或羧基或卤原子；X代表由公式表示的基团：-O-，-S-或（其中R3代表氢原子或C1-6烷基，苯基，苄基或（C1-6烷氧基）羰基）；Z代表①由一般式表示的基团：-0-（CH2）q-R5，其中q为1至3的整数，R5为卤原子或（C1-6烷氧基）羰基，芳基或杂芳基基团，②由一般式表示的基团：-0-（CH2）r-0-（CH2）s-0-R6，其中r和s分别为1至5的整数，R6为氢原子或C1-6烷基基团，③由公式表示的基团：④由一般式表示的基团：其中t为0至2的整数，A代表由一般式表示的基团：（其中B代表- NH-，-0-或-S-表示的基团），C1-6烷基，（C1-6烷氧基）羰基甲基，吡啶基或呋喃基团或由一般式表示的基团：（其中R7代表氢原子，C1-6烷基或C1-6烷氧基基团或卤原子，w代表0或1），⑤由一般式表示的基团：其中R8代表乙酰氧基或C1-6烷基基团，n为0至2的整数，m为2至10的整数，J和K可以相同或不同，分别代表氢原子或C1-6烷基基团，并且其药学上可接受的盐。还提供了包含这些衍生物的制药组合物，以及这些衍生物在制造具有治疗或预防胃溃疡价值的药物方面的用途。还提供了制备这种吡啶衍生物的方法。
• Pyridine derivatives, pharmaceutical compositions comprising the same, the use of the same for the manufacture of medicaments having therapeutic or preventative value, and process for preparing the same
  申请人：Eisai Co., Ltd.

  公开号：EP0654471A1

  公开（公告）日：1995-05-24

  The invention provides pyridine derivatives represented by general formula: wherein R¹ and R² may be the same or different from each other and each stand for a hydrogen atom, a C₁₋₆ alkyl, C₁₋₆ alkoxy, halogenated C₁₋₆ alkyl, (C₁₋₆ alkoxy)carbonyl or carboxyl group or a halogen atom; X stands for a group represented by the formula: -O-, -S- or (wherein R³ stands for a hydrogen atom or a C₁₋₆ alkyl, phenyl, benzyl or (C₁₋₆ alkoxy)carbonyl group); Z stands for ① a group represented by the general formula:         -O-(CH₂)q-R⁵ wherein q stands for an integer of 1 to 3 and R⁵ stands for a naphthyl group, which may be substituted with a C₁₋₆ alkoxy group, a hydroxyl group or a halogen atom; a pyridyl group or a furyl group, ② a group represented by the general formula:         ―OR⁹    wherein OR⁹ stands for a phenyl, tolyl, xylyl or naphthyl group, n stands for an integer of 0 to 2; m stands for an integer of 2 to 10; and J and K may be the same or different from each other and each stand for a hydrogen atom or a C₁₋₆ alkyl group, and a pharmaceutically acceptable salt thereof. Pharmaceutical compositions comprising these derivatives are also provided, together with the use of the derivatives for the manufacture of medicaments having therapeutic or preventative value in the treatment of peptic ulcers. Processes for preparing such pyridine derivatives are also provided.

  本发明提供由通式表示的吡啶衍生物： 其中 R¹ 和 R² 可以相同或互不相同，各自代表氢原子、C₁₋₆ 烷基、C₁₋₆ 烷氧基、卤代 C₁₋₆ 烷基、(C₁₋₆ 烷氧基)羰基或羧基或卤原子； X 代表由式表示的基团： -O-、-S- 或 (其中 R³ 代表氢原子或 C₁₋₆ 烷基、苯基、苄基或 (C₁₋₆ 烷氧基)羰基）； Z 代表 由通式表示的基团： -O-(CH₂)q-R⁵ 其中 q 代表 1 至 3 的整数，R⁵ 代表萘基，可被 C₁₋₆烷氧基、羟基或卤素原子、吡啶基或呋喃基取代、 由通式表示的基团： -由通式表示的基团 其中 OR𠞙 代表苯基、甲苯基、二甲苯基或萘基、 n 代表 0 至 2 的整数；m 代表 2 至 10 的整数；以及 J 和 K 可以相同或不同，各自代表一个氢原子或一个 C₁₋₆ 烷基、 及其药学上可接受的盐。 此外，还提供了包含这些衍生物的药物组合物，以及这些衍生物在制造具有治疗或预防消化性溃疡价值的药物时的用途。还提供了制备此类吡啶衍生物的工艺。
• Methods and compositions for the administration of prodrugs of proton pump inhibitors
  申请人：Hughes M. Patrick

  公开号：US20070060621A1

  公开（公告）日：2007-03-15

  Disclosed herein are methods, compositions, and dosage forms related to prodrugs of a proton pump inhibitors wherein said compositions and dosage forms do not comprise a salt of phosphoric acid. Principles related to the use of various anions and buffers in relation to these prodrugs are also disclosed.
• Methods and compositions for the treatment of conditions related to gastric acid secretion
  申请人：Shen Jie

  公开号：US20090048302A1

  公开（公告）日：2009-02-19

  A method comprising orally administering to a mammal a proton pump inhibitor, or a pharmaceutically acceptable prodrug thereof, and a compound which modulates the activity of the MRP2 or other transporter proteins involved in efflux of a proton pump inhibitor or a prodrug, is disclosed herein, said method being effective for the prevention or treatment of a disease or condition related to gastric acid secretion. This method applied to compounds which both inhibit and stimulate MRP2 activity or activity of other transporter proteins involved in efflux of a proton pump inhibitor or a prodrug. Compositions, medicaments, and experimental results related thereto are also disclosed.