[6-chloro-2-(methylthio)-5-(naphthalen-1-yloxy)-1H-benzimidazol-1-yl]methyl dihydrogen phosphate

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: [6-chloro-2-(methylthio)-5-(naphthalen-1-yloxy)-1H-benzimidazol-1-yl]methyl dihydrogen phosphate
• 英文别名: [6-chloro-2-(methylsulfanyl)-5-(naphthalen-1-yloxy)-1H-benzimidazol-1-yl]methyl phosphate；(6-Chloro-2-methylsulfanyl-5-naphthalen-1-yloxybenzimidazol-1-yl)methyl dihydrogen phosphate；(6-chloro-2-methylsulfanyl-5-naphthalen-1-yloxybenzimidazol-1-yl)methyl dihydrogen phosphate
• 化学式: C₁₉H₁₆ClN₂O₅PS
• 分子量: 450.839
• InChiKey: NVUBGUDJSSFUPE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  29
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  119
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  5-chloro-2-(methylthio)-6-(1-naphthyloxy)-1H-benzimidazol 、 二叔丁基氯甲基磷酸酯 在 sodium hydride 、 盐酸 作用下， 以 N,N-二甲基甲酰胺 、 mineral oil 、 1,4-二氧六环 为溶剂， 反应 49.0h， 生成 [5-chloro-2-(methylthio)-6-(naphthalen-1-yloxy)-1H-benzimidazol-1-yl]methyl phosphate 、 [6-chloro-2-(methylthio)-5-(naphthalen-1-yloxy)-1H-benzimidazol-1-yl]methyl dihydrogen phosphate
  参考文献：
  名称：

  A highly water soluble benzimidazole derivative useful for the treatment of fasciolosis

  摘要：

  This study describes the synthesis of compound (7), a highly hydrosoluble phosphonooxymethyl prodrug of compound alpha (4). Compound (7) improved the aqueous solubility of its precursor compound (4) by 50,000 times and it is stable at neutral pH. The prodrug showed faciolicidal activity when evaluated in vitro against excysted Fasciola hepatica metacercariae. The in vivo evaluation of (7) was carried out via oral, intramuscular and subcutaneous administration in sheep artificially infected with F. hepatica metacercariae. At an intramuscular dose of 4 mg/kg, the activity of (7) was similar to that of compound alpha (4) at an oral dose of 15 mg/kg. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.10.017

文献信息

• NOVEL HYDROSOLUBLE COMPOUNDS DERIVED FROM BENZIMIDAZOLE USED IN TREATING FASCIOLOSIS
  申请人：UNIVERSIDAD NACIONAL AUTONOMA DE MEXICO

  公开号：US20170327470A1

  公开（公告）日：2017-11-16

  The present invention relates to hydrosoluble compounds derived from benzimidazole represented by general formula I: wherein: Y 1 e Y 2 are independently O or S, and at least one of Y 1 and Y 2 is O; R 1 and R 2 are independently hydrogen or a cation, both are hydrogen or both are cations; R 3 is a C1-4 alkyl; R 4 and R 5 are independently halogen or a —OR 6 alkoxide; R 6 is C6-C10 aryl linked in 5- or 6-position of benzimidazole nucleus.

  本发明涉及由通用公式I表示的源自苯并咪唑的水溶性化合物：其中：Y1和Y2独立地为O或S，且Y1和Y2中至少一个是O；R1和R2独立地为氢或阳离子，两者均为氢或两者均为阳离子；R3是C1-4烷基；R4和R5独立地为卤素或—OR6烷氧基；R6是C6-C10芳基，连接在苯并咪唑核的5-或6-位置。
• Hydrosoluble compounds derived from benzimidazole used in treating fasciolosis
  申请人：UNIVERSIDAD NACIONAL AUTONOMA DE MEXICO

  公开号：US10239842B2

  公开（公告）日：2019-03-26

  The present invention relates to hydrosoluble compounds derived from benzimidazole represented by general formula I: wherein: Y1 e Y2 are independently O or S, and at least one of Y1 and Y2 is O; R1 and R2 are independently hydrogen or a cation, both are hydrogen or both are cations; R3 is a C1-4 alkyl; R4 and R5 are independently halogen or a —OR6 alkoxide; R6 is C6-C10 aryl linked in 5- or 6-position of benzimidazole nucleus.

  本发明涉及由通式 I 所代表的苯并咪唑衍生的水溶性化合物： 其中 Y1 e Y2 独立地为 O 或 S，且 Y1 和 Y2 中至少有一个为 O；R1 和 R2 独立地为氢或阳离子，两者均为氢或两者均为阳离子；R3 为 C1-4 烷基；R4 和 R5 独立地为卤素或 -OR6 烷氧基；R6 为连接在苯并咪唑核的 5 位或 6 位上的 C6-C10 芳基。
• A highly water soluble benzimidazole derivative useful for the treatment of fasciolosis
  作者：Miguel Flores-Ramos、Froylán Ibarra-Velarde、Alicia Hernández-Campos、Yolanda Vera-Montenegro、Helgi Jung-Cook、Germinal J. Cantó-Alarcón、Lauro Misael del Rivero、Rafael Castillo

  DOI：10.1016/j.bmcl.2014.10.017

  日期：2014.12

  This study describes the synthesis of compound (7), a highly hydrosoluble phosphonooxymethyl prodrug of compound alpha (4). Compound (7) improved the aqueous solubility of its precursor compound (4) by 50,000 times and it is stable at neutral pH. The prodrug showed faciolicidal activity when evaluated in vitro against excysted Fasciola hepatica metacercariae. The in vivo evaluation of (7) was carried out via oral, intramuscular and subcutaneous administration in sheep artificially infected with F. hepatica metacercariae. At an intramuscular dose of 4 mg/kg, the activity of (7) was similar to that of compound alpha (4) at an oral dose of 15 mg/kg. (C) 2014 Elsevier Ltd. All rights reserved.