8-N-[(2-hydroxy-4-methoxy)benzoyl]aminocaprylic acid

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 8-N-[(2-hydroxy-4-methoxy)benzoyl]aminocaprylic acid
• 英文别名: 8-(N-2-hydroxy-4-methoxybenzoyl)aminocaprylic acid；8-(N-2-hydroxy-4-methoxybenzoyl) aminocaprylic acid；8-(N-2-hydroxy-4-methoxybenzoyl)-aminocaprylic acid；8-(2-hydroxy-4-methoxybenzoylamino)caprylic acid；8-(2-hydroxy-4-methoxybenzoylamino)octanoic acid；8-[(2-Hydroxy-4-methoxybenzoyl)amino]octanoic acid
• 化学式: C₁₆H₂₃NO₅
• 分子量: 309.362
• InChiKey: QSEXGCYGWQFHIF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  22
• 可旋转键数：
  10
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  95.9
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  8-氨基辛酸 在 sodium hydroxide 作用下， 以 二氯甲烷 为溶剂， 反应 4.5h， 生成 8-N-[(2-hydroxy-4-methoxy)benzoyl]aminocaprylic acid
  参考文献：
  名称：

  Synthesis and Evaluation of Compounds That Facilitate the Gastrointestinal Absorption of Heparin

  摘要：

  A family of novel compounds (delivery agents) that promote the gastrointestinal absorption of USP heparin in rats and primates has been discovered. The delivery agents in combination with heparin were administered either orally or intracolonically in an aqueous propylene glycol solution and caused dramatic increases in both plasma heparin concentrations (anti-Factor Xa) and clotting times (APTT). Using one of the most effective delivery agents in this series, an estimated relative bioavailability of 8% can be achieved following oral administration to cynomolgus monkeys. To establish a correlation between the in vivo data and an in vitro parameter, immobilized artificial membrane (IAM) chromatography was performed. Log relative k' values were correlated to the efficiency of oral heparin delivery.

  DOI：

  10.1021/jm970811m

文献信息

• Method of preparing salicylamides
  申请人：——

  公开号：US20030216593A1

  公开（公告）日：2003-11-20

  The present invention provides a fast, high yield method for preparing salicylamide intermediates. The method comprises reacting a C 4 or higher alkyl ester of salicylic acid or derivative thereof with at least one amine selected from the group consisting of monoalkylamines, dialkylamines, ammonia, and any combination of any of the foregoing in alcohol to yield the sali-cylamide. The C 4 or higher alkyl ester of salicylic acid or a derivative thereof is preferably prepared by reacting salicylic acid or a derivative thereof with a C 4 or higher alcohol in presence of at least one of sulfuric acid, a sulfonic acid, and a mineral acid. This process for preparing salicylamide intermediates from salicylic acid or derivative thereof generally has a cycle time of about 2 days, and yields about 95% of a 99% pure material. In comparison, when a C 3 or lower alkyl ester is used in lieu of the C 4 or higher alkyl ester, the process generally has a cycle time of 7-9 days and yields about 60% of a 95% pure material. Methods of preparing an alkylated salicylamide are also provided.

  本发明提供了一种快速、高产量的制备水杨酰胺中间体的方法。该方法包括将水杨酸的C4或更高烷基酯或其衍生物与来自单烷基胺、二烷基胺、氨和上述任何组合的至少一种胺在醇中反应，以产生水杨酰胺。水杨酸的C4或更高烷基酯或其衍生物通常是通过将水杨酸或其衍生物与C4或更高醇在硫酸、磺酸和矿酸中的至少一种存在下反应制备的。从水杨酸或其衍生物制备水杨酰胺中间体的这一过程通常具有约2天的周期时间，并产生约95%的99%纯度物质。相比之下，当使用C3或更低烷基酯代替C4或更高烷基酯时，该过程通常具有7-9天的周期时间，并产生约60%的95%纯度物质。还提供了制备烷基化水杨酰胺的方法。
• Oral B12 Therapy
  申请人：Castelli Cristina

  公开号：US20110207693A1

  公开（公告）日：2011-08-25

  Methods of normalizing vitamin B 12 levels in patients with low vitamin B 12 and methods of normalizing intersubject variability in the treatment of such patients are described. Methods of reducing MMA and/or homocysteine levels, and pharmaceutical compositions useful to effect such changes are also described.

  本文描述了治疗低维生素B12患者的维生素B12水平正常化方法以及正常化患者治疗间个体差异的方法。同时，还描述了降低MMA和/或同型半胱氨酸水平的方法，以及用于实现这些变化的药物组合。
• ORAL B12 THERAPY
  申请人：CASTELLI Cristina

  公开号：US20160074420A1

  公开（公告）日：2016-03-17

  Methods of normalizing vitamin B 12 levels in patients with low vitamin B 12 and methods of normalizing intersubject variability in the treatment of such patients are described. Methods of reducing MMA and/or homocysteine levels, and pharmaceutical compositions useful to effect such changes are also described.

  本文描述了在患有低维生素B12的患者中规范化维生素B12水平的方法，以及规范化治疗这些患者的主体间变异性的方法。还描述了降低MMA和/或同型半胱氨酸水平的方法，以及用于实现这些变化的制药组合物。
• Disodium salts, monohydrates, and ethanol solvates for delivering active agents
  申请人：Emisphere Technologies, Inc.

  公开号：US20040106825A1

  公开（公告）日：2004-06-03

  The inventors have discovered that the disodium salt of certain delivery agents has surprisingly greater efficacy for delivering active agents than the corresponding monosodium salt. Furthermore, the inventors have discovered that the disodium salts of these delivery agents form solvates with ethanol and hydrates with water. The delivery agents have the formula 1 wherein R 1 , R 2 , R 3 , and R 4 are indepedently hydrogen, halogen, C 1 -C 4 alkyl, or C 1 -C 4 alkoxy; and R 5 is a substitued or unsubstituted C 2 -C 16 alkylene, substituted or unsubstituted C 2 -C 16 alkenylene, substituted or unsubstituted C 1 -C 12 alkyl(arylene), or substituted or unsubstituted aryl(C 1 -C 12 alkylene). The hydrates and solvates of present invention also have surprisingly greater efficacy for delivering active agents, such as heparin and calcitonin, than their corresponding monosodium salts and free acids. The present invention provides an alcohol solvate, such as ethanol solvate, of a disodium salt of a delivery agent of the formula above. The invention also provides a hydrate of a disodium salt of a delivery agent of the formula above. Preferred delivery agents include, but are not limited to, N-(5-chlorosalicyloyl)-8-aminocaprylic acid (5-CNAC), N-(10-[2-hydroxybenzoyl]amino)decanoic acid (SNAD), and sodium N-(8-[2-hydroxybenzoyl]amino)caprylate (SNAC). The invention also provides methods of preparing the disodium salt, ethanol solvate, and hydrate and compositions containing the disodium salt, ethanol solvate, and/or hydrate.

  发明者发现，某些传递剂的二钠盐比相应的单钠盐具有更出色的传递活性剂的功效。此外，发明者还发现这些传递剂的二钠盐与乙醇形成溶剂合物，与水形成水合物。传递剂的公式为1，其中R1、R2、R3和R4分别为氢、卤素、C1-C4烷基或C1-C4烷氧基；R5是取代或未取代的C2-C16烷基、取代或未取代的C2-C16烯基、取代或未取代的C1-C12烷基（芳基）或取代或未取代的芳基（C1-C12烷基）。本发明的水合物和溶剂合物比它们的相应单钠盐和自由酸具有更出色的传递活性剂的功效，例如肝素和降钙素。本发明提供了公式如上的传递剂的二钠盐的醇溶剂，例如乙醇溶剂。本发明还提供了公式如上的传递剂的二钠盐的水合物。优选的传递剂包括但不限于N-(5-氯水杨酰基)-8-氨基己酸（5-CNAC）、N-(10-[2-羟基苯甲酰基]氨基)癸酸（SNAD）和N-(8-[2-羟基苯甲酰基]氨基)癸酸钠（SNAC）。本发明还提供了制备二钠盐、醇溶剂和水合物以及含有二钠盐、醇溶剂和/或水合物的组合物的方法。
• Method of preparing alkylated salicylamides via a dicarboxylate intermediate
  申请人：——

  公开号：US20030096992A1

  公开（公告）日：2003-05-22

  The present invention relates to a method of preparing an alkylated salicylamide from a protected and activated salicylamide via a dicarboxylated salicylamide intermediate. The present invention also relates to dicarboxylic salicylamide delivery agent compounds for the delivery of active agents. Methods of administration are provided as well.

  本发明涉及一种从受保护和活化的水杨酰胺经过二羧基化的水杨酰胺中间体制备烷基化水杨酰胺的方法。本发明还涉及用于传递活性剂的二羧基水杨酰胺传递剂化合物。本发明还提供了给药方法。