methyl N-[6-(benzenesulfinyl)-1-(phosphonooxymethyl)benzimidazol-2-yl]carbamate | 923672-38-2

• 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: methyl N-[6-(benzenesulfinyl)-1-(phosphonooxymethyl)benzimidazol-2-yl]carbamate
• CAS: 923672-38-2
• 化学式: C₁₆H₁₆N₃O₇PS
• 分子量: 425.359
• InChiKey: LBZMSBOMCWPMIK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.4
• 重原子数：
  28
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  159
• 氢给体数：
  3
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  奥吩达唑 、 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 、 1,4-二氧六环 为溶剂， 反应 5.0h， 生成 methyl N-[6-(benzenesulfinyl)-1-(phosphonooxymethyl)benzimidazol-2-yl]carbamate 、 methyl N-[5-(benzenesulfinyl)-1-(phosphonooxymethyl)benzimidazol-2-yl]carbamate
  参考文献：
  名称：

  Highly Water-Soluble Prodrugs of Anthelmintic Benzimidazole Carbamates: Synthesis, Pharmacodynamics, and Pharmacokinetics

  摘要：

  Highly water-soluble prodrugs 1a - g of anthelmintic benzimidazole carbamates 2a - g were synthesized. These prodrugs combine high aqueous solubility and stability with high lability in the presence of alkaline phosphatases. The veterinary utility of 1a was shown by a pharmacodynamic and pharmacokinetic study performed. in swine. Comparable anthelmintic efficacy was observed with prodrug la or the parent fenbendazole 2a. The pharmacokinetic results showed that 2a is better absorbed when derived from 1a than when applied as such.

  DOI：

  10.1021/jm701456r

文献信息

• Novel Benzimidazole(Thio)Carbamates with Antiparasitic Activity and the Synthesis Thereof
  申请人：Chassaing Christophe Pierre Alain

  公开号：US20090131369A1

  公开（公告）日：2009-05-21

  This invention relates to benzimidazole carbamates and (thio)carbamates corresponding to Formula I: Here, X 1 and X 2 are independently O or S, wherein at least one of X 1 and X 2 is O; Y 1 and Y 2 are independently O or S, wherein at least one of Y 1 and Y 2 is O; R 1 is alkyl having from 1-4 carbon atoms; R 2 , R 3 , and R 4 are independently hydrogen or a cation; R 5 and R 6 are independently hydrogen, halogen, alkyl (having from 1-8 carbon atoms), —OR 7 , —SR 8 , —CO—R 9 , —OSO 2 —Ar, or —S(O)R 10 ; R 7 is alkyl having from 1-8 carbon atoms; R 8 is alkyl (having from 1-8 carbon atoms) or aryl; R 9 is alkyl (having from 1-8 carbon atoms), cycloalkyl (having from 3-6 carbon atoms), or aryl; Ar is aryl; and R 10 is alkyl (having from 1-8 carbon atoms) or aryl. The compounds generally are soluble and stable in water, and have antiparasitic (particularly anthelmintic) activity in vivo that is comparable to known water-insoluble benzimidazole carbamates (e.g., albendazole and fenbendazole).

  本发明涉及与式I相对应的苯并咪唑氨基甲酸酯和（硫）氨基甲酸酯，其中，X1和X2独立地为O或S，其中至少一个为O；Y1和Y2独立地为O或S，其中至少一个为O；R1为具有1-4个碳原子的烷基；R2、R3和R4独立地为氢或阳离子；R5和R6独立地为氢、卤素、烷基（具有1-8个碳原子）、-OR7、-SR8、-CO-R9、-OSO2-Ar或-S（O）R10；R7为具有1-8个碳原子的烷基；R8为烷基（具有1-8个碳原子）或芳基；R9为烷基（具有1-8个碳原子）、环烷基（具有3-6个碳原子）或芳基；Ar为芳基；R10为烷基（具有1-8个碳原子）或芳基。这些化合物通常在水中是可溶且稳定的，并且在体内具有抗寄生虫（特别是驱虫）活性，与已知的水不溶性苯并咪唑氨基甲酸酯（例如阿苯达唑和氟苯达唑）相当。
• NOVEL BENZIMIDAZOLE (THIO) CARBAMATES WITH ANTIPARASITIC ACTIVITY AND THE SYNTHESIS THEREOF
  申请人：Intervet International BV

  公开号：EP1913009B1

  公开（公告）日：2010-05-12
• US7893271B2
  申请人：——

  公开号：US7893271B2

  公开（公告）日：2011-02-22
• Highly Water-Soluble Prodrugs of Anthelmintic Benzimidazole Carbamates: Synthesis, Pharmacodynamics, and Pharmacokinetics
  作者：C. Chassaing、M. Berger、A. Heckeroth、T. Ilg、M. Jaeger、C. Kern、K. Schmid、M. Uphoff

  DOI：10.1021/jm701456r

  日期：2008.3.13

  Highly water-soluble prodrugs 1a - g of anthelmintic benzimidazole carbamates 2a - g were synthesized. These prodrugs combine high aqueous solubility and stability with high lability in the presence of alkaline phosphatases. The veterinary utility of 1a was shown by a pharmacodynamic and pharmacokinetic study performed. in swine. Comparable anthelmintic efficacy was observed with prodrug la or the parent fenbendazole 2a. The pharmacokinetic results showed that 2a is better absorbed when derived from 1a than when applied as such.