5-difluoromethoxy-2-[(4-methoxy-3-methyl-pyridin-2-yl)methylsulfinyl]-1H-benzimidazole | 97964-05-1

• 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: 5-difluoromethoxy-2-[(4-methoxy-3-methyl-pyridin-2-yl)methylsulfinyl]-1H-benzimidazole
• 英文别名: 5-difluoromethoxy-2-[(4-methoxy-3-methyl-2-pyridyl)methylsulfinyl]-1H-benzimidazole；pantoprazole；5-Difluoromethoxy-2-[(4-methoxy-3-methyl-2-pyridinyl)methylsulfinyl]-1H-benzimidazole；6-(difluoromethoxy)-2-[(4-methoxy-3-methylpyridin-2-yl)methylsulfinyl]-1H-benzimidazole
• CAS: 97964-05-1
• 化学式: C₁₆H₁₅F₂N₃O₃S
• 分子量: 367.376
• InChiKey: ASWLZURXLWNOQA-UHFFFAOYSA-N

物化性质

• 沸点：
  591.0±60.0 °C(Predicted)
• 密度：
  1.48±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  25
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  96.3
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  2,3-二甲基-4-甲氧基吡啶氮氧化物 在 sodium hydroxide 、 氯化亚砜 、 乙酸酐 、 间氯过氧苯甲酸 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 10.5h， 生成 5-difluoromethoxy-2-[(4-methoxy-3-methyl-pyridin-2-yl)methylsulfinyl]-1H-benzimidazole
  参考文献：
  名称：

  （H +，K +）-ATPase抑制2-[（（2-吡啶基甲基）亚磺酰基]苯并咪唑 4.具有增加的选择性的一系列新的二甲氧基吡啶基取代的抑制剂。选择of托拉唑作为临床候选药物。

  摘要：

  [（吡啶基甲基）亚磺酰基]苯并咪唑1（PSBs）是一类高度有效的抗分泌（H +，K +）-ATPase抑制剂，需要通过酸激活才能形成其活性成分，即环亚磺酰胺4。（H + ，K +）-ATPase在体内仅在低pH时会产生非选择性的亲硫基4，从而避免了与体内其他巯基的相互作用。进行酸催化转化的倾向取决于2形成中所涉及的官能团的亲核/亲电性质，因为该步骤既决定速率又取决于pH。这项研究的目的是鉴定在具有酸性pH值的刺激胃腺中具有高（H +，K +）-ATPase抑制活性的化合物，但在体外pH值（Na +，K +）-ATPase抑制活性。仔细研究了所有衍生物中存在的吡啶4-甲氧基取代基侧面的取代基的关键影响。3-甲氧基的引入使得抑制剂具有与奥美拉唑和兰索拉唑相似的高效力组合，但是增加了稳定性。这些研究的结果是，化合物1a（INN top托拉唑）被选作候选药物，目前正在进行III期临床研究。

  DOI：

  10.1021/jm00084a010

文献信息

• Anti-sekretorische, Fluoralkoxy-substituierte Pyridylmethylthio-(oder sulfinyl-)benzimidazole
  申请人：Byk Gulden Lomberg Chemische Fabrik GmbH

  公开号：EP0134400B1

  公开（公告）日：1993-03-24
• Controlled-release pharmaceutical composition and method for producing the same
  申请人：Yoshitake Takashi

  公开号：US20070110806A1

  公开（公告）日：2007-05-17

  It is an object of the present invention, in the case of a controlled-release pharmaceutical composition, particularly a pulsed-release pharmaceutical composition, containing an acid-unstable physiologically active substance, to provide a pharmaceutical composition having little variation in dissolution lag time and high reliability of dissolution characteristics. The present invention discloses a controlled-release pharmaceutical composition comprising: 1) a core containing an acid-unstable physiologically active substance and a disintegrant; and 2) a release-controlling coating which covers the core, and which contains a water-insoluble polymer, an enteric polymer and a hydrophobic wax.
• Controlled-Release Pharmaceutical Composition and Method for Producing the Same
  申请人：Yoshitake Takashi

  公开号：US20080095839A1

  公开（公告）日：2008-04-24

  It is an object of the present invention, in the case of a controlled-release pharmaceutical composition, particularly a pulsed-release pharmaceutical composition, containing an acid-unstable physiologically active substance, to provide a pharmaceutical composition having little variation in dissolution lag time and high reliability of dissolution characteristics. The present invention discloses a controlled-release pharmaceutical composition comprising: 1) a core containing an acid-unstable physiologically active substance and a disintegrant; and 2) a release-controlling coating which covers the core, and which contains a water-insoluble polymer, an enteric polymer and a hydrophobic wax.
• PULSED-RELEASE PREPARATION HAVING IMPROVED DISINTEGRATION PROPERTIES IN VIVO
  申请人：Zaima Yasuhiro

  公开号：US20090148519A1

  公开（公告）日：2009-06-11

  An object of the present invention is to provide a pulsed-release preparation that achieves pulsed-release by coating the exterior of a core that contains a physiologically active substance and a disintegrant, with a controlled-release coating that contains a water-insoluble polymer and an enteric polymer, or a water-insoluble polymer and a water-soluble polymer, wherein a satisfactory pulsed-release can be achieved without increasing the amount of disintegrant in the core, in particular even in the low-water environment in the lower part of the digestive tract. The present invention provides a pulsed-release preparation comprising: 1) a core containing a physiologically active substance and a disintegrant; 2) an enteric coating that covers the core; and 3) a controlled-release coating that covers the enteric coating applied on the core and that contains a water-insoluble polymer and an enteric polymer or water-soluble polymer.
• Oral Pharmaceutical Dosage Forms Comprising a Proton Pump Inhibitor and a NSAID
  申请人：Depui Helene

  公开号：US20090297594A1

  公开（公告）日：2009-12-03

  An oral pharmaceutical dosage form comprising an acid susceptible proton pump inhibitor and one or more NSAIDs in a fixed formulation, wherein the proton pump inhibitor is protected by an enteric coating layer. The fixed formulation is in the form of an enteric coating layered tablet, a capsule or a multiple unit tableted dosage form. The multiple unit dosage forms are most preferred. The new fixed formulation is especially useful in the treatment of gastrointestinal side-effects associated with NSAID treatment.