[3-Methyl-4-(2,2,3,3,3-pentafluoro-propoxy)-pyridin-2-yl]-methanol | 103577-68-0

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: [3-Methyl-4-(2,2,3,3,3-pentafluoro-propoxy)-pyridin-2-yl]-methanol
• 英文别名: 2-Hydroxymethyl-3-methyl-4-(2,2,3,3,3-pentafluoropropoxy)pyridine；[3-methyl-4-(2,2,3,3,3-pentafluoropropoxy)pyridin-2-yl]methanol
• CAS: 103577-68-0
• 化学式: C₁₀H₁₀F₅NO₂
• 分子量: 271.187
• InChiKey: FZSZUDXAPZXBME-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  42.4
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  [3-Methyl-4-(2,2,3,3,3-pentafluoro-propoxy)-pyridin-2-yl]-methanol 在 氯化亚砜 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 生成 2-Chloromethyl-3-methyl-4-(2,2,3,3,3-pentafluoro-propoxy)-pyridine
  参考文献：
  名称：

  2-[（（2-吡啶基甲基）亚磺酰基] -1H-噻吩并[3,4-d]咪唑。一类新型的胃H + / K（+）-ATPase抑制剂。

  摘要：

  合成2-[（（2-吡啶基甲基）亚磺酰基]噻吩并咪唑类化合物，并研究其作为胃H + / K（+）-ATPase的潜在抑制剂。已发现两种可能的噻吩并咪唑系列的[3,4-d]异构体在体外和体内都是有效的胃酸分泌抑制剂。结构活性关系表明，特别是在吡啶部分的4位具有额外的电子要求特性的亲脂性烷氧基，苄氧基和苯氧基取代基与未取代的噻吩并[3,4-d]咪唑结合会导致具有高活性的化合物。良好的化学稳定性。噻吩并[3,4-d]咪唑部分的各种取代方式导致较低的生物活性。选择了七氟丁氧基衍生物萨维拉唑（HOE 731，5d）进行进一步开发，目前正在临床评估中。

  DOI：

  10.1021/jm00081a004
• 作为产物：
  描述：

  2,3-Dimethyl-4-(2,2,3,3,3-pentafluoropropoxy)pyridine N-oxide 在 sodium hydroxide 、 硫酸 、 乙酸酐 作用下， 生成 [3-Methyl-4-(2,2,3,3,3-pentafluoro-propoxy)-pyridin-2-yl]-methanol
  参考文献：
  名称：

  Synthesis of 2-(((4-fluoroalkoxy-2-pyridyl)methyl)sulfinyl)-1H-benzimidazoles as antiulcer agents.

  摘要：

  合成了许多2-[[（4-氟烷氧基-2-吡啶基）甲基]亚磺酰基]-1H-苯并咪唑，并测试了其抗分泌、抗溃疡和细胞保护活性。这些化合物在抗分泌和抗溃疡效能方面大多优于奥美拉唑，尤其是在保护胃黏膜免受乙醇诱导损伤方面。在这些化合物中，2-[[[3-甲基-4-(2,2,2-三氟乙氧基)-2-吡啶基]甲基]亚磺酰基]-1H-苯并咪唑，AG-1749（兰索拉唑）（6f）被选中进行进一步开发和临床评估。

  DOI：

  10.1248/cpb.38.2853

文献信息

• Synthesis of 2-(((4-fluoroalkoxy-2-pyridyl)methyl)sulfinyl)-1H-benzimidazoles as antiulcer agents.
  作者：Keiji KUBO、Katsuaki ODA、Tatsuhiko KANEKO、Hioroshi SATOH、Akira NOHARA

  DOI：10.1248/cpb.38.2853

  日期：——

  Many 2-[[(4-fluoroalkoxy-2-pyridyl)methyl]sulfinyl]-1H-benzimidazoles were synthesized and tested for antisecretory, antiulcer, and cytoprotective activities. Most of these compounds were superior to omeprazole in antisecretory and antiulcer potencies, and especially in protecting the gastric mucosa from ethanol-induced damage. Among these compounds 2-[[[3-methyl-4-(2, 2, 2-trifluoroethoxy)-2-pyridyl]methyl]sulfinyl]-1H-benzimidazole, AG-1749 (lansoprazole) (6f), was selected for further development and clinical evaluation.

  合成了许多2-[[（4-氟烷氧基-2-吡啶基）甲基]亚磺酰基]-1H-苯并咪唑，并测试了其抗分泌、抗溃疡和细胞保护活性。这些化合物在抗分泌和抗溃疡效能方面大多优于奥美拉唑，尤其是在保护胃黏膜免受乙醇诱导损伤方面。在这些化合物中，2-[[[3-甲基-4-(2,2,2-三氟乙氧基)-2-吡啶基]甲基]亚磺酰基]-1H-苯并咪唑，AG-1749（兰索拉唑）（6f）被选中进行进一步开发和临床评估。
• Stabilized pharmaceutical composition
  申请人：TAKEDA CHEMICAL INDUSTRIES, LTD.

  公开号：US20040209919A1

  公开（公告）日：2004-10-21

  The pharmaceutical composition of the invention, which comprises a benzimidazole compound of the formula 1 wherein R 1 is hydrogen, alkyl, halogen, cyano, carboxy, carboalkoxy, carboalkoxyalkyl, carbamoyl, carbamoylalkyl, hydroxy, alkoxy, hydroxyalkyl, trifluoromethyl, acyl, carbamoyloxy, nitro, acyloxy, aryl, aryloxy, alkylthio or alkylsulfinyl, R 2 is hydrogen, alkyl, acyl, carboalkoxy, carbamoyl, alkylcarbamoyl, dialkylcarbamoyl, alkylcarbonylmethyl, alkoxycarbonylmethyl or alkylsulfonyl, R 3 and R 5 are the same or different and each is hydrogen, alkyl, alkoxy or alkoxyalkoxy, R 4 is hydrogen, alkyl, alkoxy which may optionally be fluorinated, or alkoxyalkoxy, and m is an integer of 0 through 4, and a basic inorganic salt stabilizing agent, is physically stable. Magnesium and calcium basic inorganic salt stabilizing agents are particularly useful.

  本发明的药物组合物包括式1中的苯并咪唑化合物，其中R1为氢、烷基、卤素、氰基、羧基、羧基烷氧基、羧基烷氧基烷基、氨基甲酰基、氨基甲酰基烷基、羟基、烷氧基、羟基烷基、三氟甲基、酰基、氨基甲酰氧基、硝基、酰氧基、芳基、芳氧基、烷硫基或烷基亚磺酰基；R2为氢、烷基、酰基、羧基烷氧基、氨基甲酰基、烷基氨基甲酰基、二烷基氨基甲酰基、烷基羰基甲基、烷氧羰基甲基或烷基磺酰基；R3和R5相同或不同，均为氢、烷基、烷氧基或烷氧基烷基；R4为氢、烷基、烷氧基（可选择性地氟化）或烷氧基烷基；m为0到4的整数；以及一种碱性无机盐稳定剂，具有物理稳定性。镁和钙的碱性无机盐稳定剂尤其有用。
• Stabilized pharmaceutical composition and its production
  申请人：Takeda Chemical Industries, Ltd.

  公开号：US20020039598A1

  公开（公告）日：2002-04-04

  The pharmaceutical composition of the invention, which comprises a benzimidazole compound of the formula 1 wherein R 1 is hydrogen, alkyl, halogen, cyano, carboxy, carboalkoxy, carboalkoxyalkyl, carbamoyl, carbamoylalkyl, hydroxy, alkoxy, hydroxyalkyl, trifluoromethyl, acyl, carbamoyloxy, nitro, acyloxy, aryl, aryloxy, alkylthio or alkylsulfinyl, R 2 is hydrogen, alkyl, acyl, carboalkoxy, carbamoyl, alkylcarbamoyl, dialkylcarbamoyl, alkylcarbonylmethyl, alkoxycarbonylmethyl or alkylsulfonyl, R 3 and R 5 are the same or different and each is hydrogen, alkyl, alkoxy or alkoxyalkoxy, R 4 is hydrogen, alkyl, alkoxy which may optionally be fluorinated, or alkoxyalkoxy, and m is an integer of 0 through 4, and a basic inorganic salt stabilizing agent, is physically stable. Magnesium and calcium basic inorganic salt stabilizing agents are particularly useful.

  本发明的药物组合物包括式1中的苯并咪唑化合物，其中R1为氢、烷基、卤素、氰基、羧基、羧基烷氧基、羧基烷氧基烷基、氨基甲酰基、氨基甲酰基烷基、羟基、烷氧基、羟基烷基、三氟甲基、酰基、氨基甲氧基、硝基、酰氧基、芳基、芳基氧基、烷基硫基或烷基亚磺酰基，R2为氢、烷基、酰基、羧基烷氧基、氨基甲酰基、烷基氨基甲酰基、二烷基氨基甲酰基、烷基甲酰基甲基、烷氧基甲酰氧基甲基或烷基磺酰基，R3和R5相同或不同，且均为氢、烷基、烷氧基或烷氧基烷基，R4为氢、烷基、可选氟化的烷氧基或烷氧基烷基，m为0到4的整数，以及一种碱性无机盐稳定剂，具有物理稳定性。镁和钙碱性无机盐稳定剂特别有用。
• Method to stabilize a pharmaceutical composition and its production
  申请人：Takeda Chemical Industries, Ltd.

  公开号：US05639478A1

  公开（公告）日：1997-06-17

  The pharmaceutical composition of the invention, which comprises a benzimidazole compound of the formula ##STR1## wherein R.sup.1 is hydrogen, alkyl, halogen, cyano, carboxy, carboalkoxy, carboalkoxyalkyl, carbamoyl, carbamoylalkyl, hydroxy, alkoxy, hydroxyalkyl, trifluoromethyl, acyl, carbamoyloxy, nitro, acyloxy, aryl, aryloxy, alkylthio or alkylsulfinyl, R.sup.2 is hydrogen, alkyl, acyl, carboalkoxy, carbamoyl, alkylcarbamoyl, dialkylcarbamoyl, alkylcarbonylmethyl, alkoxycarbonylmethyl or alkylsulfonyl, R.sup.3 and R.sup.5 are the same or different and each is hydrogen, alkyl, alkoxy or alkoxyalkoxy, R.sup.4 is hydrogen, alkyl, alkoxy which may optionally be fluorinated, or alkoxyalkoxy, and m is an integer of 0 through 4, and a basic inorganic salt stabilizing agent, is physically stable. Magnesium and calcium basic inorganic salt stabilizing agents are particularly useful.

  本发明的药物组合物包括一种苯并咪唑化合物，其化学式为##STR1##其中R.sup.1是氢、烷基、卤素、氰基、羧基、羧基烷氧基、羧基烷氧基烷基、氨基甲酰基、氨基甲酰基烷基、羟基、烷氧基、羟基烷基、三氟甲基、酰基、氨基甲酰氧基、硝基、酰氧基、芳基、芳氧基、烷硫基或烷基磺酰基，R.sup.2是氢、烷基、酰基、羧基烷氧基、氨基甲酰基、烷基氨基甲酰基、二烷基氨基甲酰基、烷基甲酰基甲基、烷氧基甲酰基甲基或烷基磺酰基，R.sup.3和R.sup.5相同或不同，分别是氢、烷基、烷氧基或烷氧基烷基，R.sup.4是氢、烷基、烷氧基（可选择氟化）或烷氧基烷基，m是0到4的整数，以及一种基础无机盐稳定剂，具有物理稳定性。镁和钙基础无机盐稳定剂特别有用。
• Process for producing stabilized pharmaceutical composition
  申请人：Takeda Chemical Industries, Ltd.

  公开号：US06017560A1

  公开（公告）日：2000-01-25

  The pharmaceutical composition of the invention, which comprises a benzimidazole compound of the formula ##STR1## wherein R.sup.1 is hydrogen, alkyl, halogen, cyano, carboxy, carboalkoxy, carboalkoxyalkyl, carbamoyl, carbamoylalkyl, hydroxy, alkoxy, hydroxyalkyl, trifluoromethyl, acyl, carbamoyloxy, nitro, acyloxy, aryl, aryloxy, alkylthio or alkylsulfinyl, R.sup.2 is hydrogen, alkyl, acyl, carboalkoxy, carbamoyl, alkylcarbamoyl, dialkylcarbamoyl, alkylcarbonyl methyl, alkoxycarbonylmethyl or alkylsulfonyl, R.sup.3 and R.sup.5 are the same or different and each is hydrogen, alkyl, alkoxy or alkoxyalkoxy, R.sup.4 is hydrogen, alkyl, alkoxy which may optionally be fluorinated, or alkoxyalkoxy, and m is an integer of 0 through 4, and a basic inorganic salt stabilizing agent, is physically stable. Magnesium and calcium basic inorganic salt stabilizing agents are particularly useful.

  该发明的药物组合物包括一种苯并咪唑化合物，其化学式为##STR1## 其中R.sup.1是氢，烷基，卤素，氰基，羧基，羧基烷氧基，羧基烷氧基烷基，氨基甲酰基，氨基甲酰基烷基，羟基，烷氧基，羟基烷基，三氟甲基，酰基，氨基甲氧基，硝基，酰氧基，芳基，芳氧基，烷硫基或烷基磺酰基，R.sup.2是氢，烷基，酰基，羧基烷氧基，氨基甲酰基，烷基氨基甲酰基，二烷基氨基甲酰基，烷基甲酰基甲基，烷氧基甲酰氧甲基或烷基磺酰基，R.sup.3和R.sup.5相同或不同，且每个都是氢，烷基，烷氧基或烷氧基烷基，R.sup.4是氢，烷基，烷氧基（可选择性氟化）或烷氧基烷基，m为0到4的整数，并且具有一种基础无机盐稳定剂，具有物理稳定性。镁和钙基础无机盐稳定剂特别有用。