(6-phenylsulfanyl-1-phosphonooxymethyl-1H-benzoimidazol-2-yl)carbamic acid methyl ester

• 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: (6-phenylsulfanyl-1-phosphonooxymethyl-1H-benzoimidazol-2-yl)carbamic acid methyl ester
• 英文别名: (6-phenylsulfanyl-1-phosphonooxymethyl-1(H)-benzoimidazol-2-yl)-carbamic acid methyl ester；methyl N-[6-phenylsulfanyl-1-(phosphonooxymethyl)benzimidazol-2-yl]carbamate
• 化学式: C₁₆H₁₆N₃O₆PS
• 分子量: 409.359
• InChiKey: YACBZDYSMRUYGR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  27
• 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：
  148
• 氢给体数：
  3
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  (6-phenylsulfanyl-1-phosphonooxymethyl-1H-benzoimidazol-2-yl)carbamic acid methyl ester 、 (5-phenylsulfanyl-1-phosphonooxymethyl-1H-benzoimidazol-2-yl)carbamic acid methyl ester 在 sodium methylate 作用下， 以 甲醇 为溶剂， 生成 (5-phenylsulfanyl-1-phosphonooxymethyl-1(H)-benzoimidazol-2-yl)-carbamic acid methyl ester di-sodium salt 、 (6-phenylsulfanyl-1-phosphonooxymethyl-1H-benzoimidazol-2-yl)carbamic acid methyl ester disodium salt
  参考文献：
  名称：

  WO2007/14846

  摘要：

  公开号：
• 作为产物：
  描述：

  芬苯达唑 、 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 (6-phenylsulfanyl-1-phosphonooxymethyl-1H-benzoimidazol-2-yl)carbamic acid methyl ester 、 (5-phenylsulfanyl-1-phosphonooxymethyl-1H-benzoimidazol-2-yl)carbamic acid methyl ester
  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
• [EN] NOVEL BENZIMIDAZOLE (THIO) CARBAMATES WITH ANTIPARASITIC ACTIVITY AND THE SYNTHESIS THEREOF<br/>[FR] NOUVEAUX BENZIMIDAZOLYL(THIO)CARBAMATES AYANT UNE ACTIVITÉ ANTIPARASITAIRE ET SYNTHÈSE DE CEUX-CI
  申请人：INTERVET INT BV

  公开号：WO2007014846A1

  公开（公告）日：2007-02-08

  [EN] The present invention is concerned with novel benzimidazole (thio)carbamates with antiparasitic activity. The present invention provides compounds of the following general formula (I) wherein X¹ and X² are O or S, wherein at least one of X¹ and X² is O, Y¹ and Y² are O or S, wherein at least one of Y¹ and Y² is O, R¹ is alkyl of 1-4 carbon atoms, R², R³ and R⁴ are independently of each other hydrogen, or a cation, R⁵ and R⁶ may both independently be hydrogen or halogen or alkyl having from 1-8 carbon atoms, or -OR⁷, wherein R⁷ is alkyl having from 1-8 carbon atoms, or -SR⁸, wherein R⁸ may be alkyl having from 1-8 carbon atoms, or aryl, or -CO-R⁹, wherein R⁹ is alkyl having from 1-8 carbon atoms, cycloalkyl having from 3-6 carbon atoms, or R⁹ is aryl, or -OSO₂-Ar, wherein Ar is aryl, or -S(O)R¹⁰, wherein R¹⁰ is alkyl having from 1-8 carbon atoms, or wherein R¹⁰ is aryl. The compounds of the invention are highly soluble and stable in water. Moreover, it has been found that the compounds according to the invention are stable for over 8 hours at pH 5 and at pH 9, which are the lower and upper pH limits at which compounds should be stable for over 8 hours in order to be suitable for drinking water application. The compounds of the present invention have excellent antiparasitic, and especially anthelmintic activity in vivo, which is comparable to the state of the art, water insoluble, benzimidazole carbamates such as albendazole and fenbendazole.
  [FR] La présente invention concerne de nouveaux benzimidazolyl(thio)carbamates ayant une activité antiparasitaire. La présente invention concerne des composés répondant à la formule générale (I) suivante dans laquelle X¹ et X² sont chacun O ou S, au moins l'un de X¹ et de X² étant O, Y¹ et Y² sont chacun O ou S, au moins l'un de Y¹ et de Y² étant O, R¹ est un alkyle ayant 1 à 4 atomes de carbone, R², R³ et R⁴ sont chacun indépendamment des autres un hydrogène ou un cation, R⁵ et R⁶ peuvent être chacun indépendamment de l'autre un hydrogène ou un halogène ou un alkyle ayant de 1 à 8 atomes de carbone, ou -OR⁷, R⁷ étant un alkyle ayant de 1 à 8 atomes de carbone, ou -SR⁸, R⁸ pouvant être un alkyle ayant de 1 à 8 atomes de carbone ou un aryle, ou -CO-R⁹, R⁹ étant un alkyle ayant de 1 à 8 atomes de carbone, un cycloalkyle ayant de 3 à 6 atomes de carbone ou bien R⁹ étant un aryle, ou -OSO₂-Ar, Ar étant un aryle, ou -S(O)R¹⁰, R¹⁰ étant un alkyle ayant de 1 à 8 atomes de carbone ou bien R¹⁰ étant un aryle. Les composés de l'invention sont extrêmement solubles et stables dans l'eau. De plus, on a trouvé que les composés selon l'invention sont stables pendant plus de 8 heures à pH 5 et à pH 9, lesquels pH sont les limites inférieure et supérieure des pH auxquels les composés devraient être stables pendant plus de 8 heures afin de convenir pour une application d'eau potable. Les composés de la présente invention ont une excellente activité antiparasitaire et en particulier anthelminthique in vivo, laquelle est comparable à celle des benzimidazolylcarbamates insolubles dans l'eau de l'art antérieur tels que l'albendazole et le fenbendazole.
• WO2007/14846
  申请人：——

  公开号：——

  公开（公告）日：——