(6R,S)-tetrahydrofolic acid

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 蝶啶及其衍生物
• 英文名称: (6R,S)-tetrahydrofolic acid
• 英文别名: 2-Amino-6-[[4-(1-carboxybutylcarbamoyl)anilino]methyl]-4-oxo-3,5,7,8-tetrahydropteridine-6-carboxylic acid；2-amino-6-[[4-(1-carboxybutylcarbamoyl)anilino]methyl]-4-oxo-3,5,7,8-tetrahydropteridine-6-carboxylic acid
• 化学式: C₂₀H₂₅N₇O₆
• 分子量: 459.462
• InChiKey: JWMATLUMSKEMKY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  33
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  207
• 氢给体数：
  8
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  (6R,S)-tetrahydrofolic acid 在 氯化镁 作用下， 以 乙醇 、 水 为溶剂， 生成 magnesium salt of (6R,S)-tetrahydrofolic acid
  参考文献：
  名称：

  Stable crystalline tetrahydrofolic acid salts

  摘要：

  本发明涉及(6R,S)-、(6S)-和(6R)-四氢叶酸的稳定晶体盐，以及制备这些盐的方法和它们作为药物和制药制剂生产成分的用途。

  公开号：

  US05817659A1

文献信息

• FOLATES, COMPOSITIONS AND USES THEREOF
  申请人：Valoti Ermanno

  公开号：US20090209543A1

  公开（公告）日：2009-08-20

  The present invention relates to folates, compositions and uses thereof; In particular, this invention describes a crystalline or amorphous compound which is a substituted or unsubstituted folate or a reduced folate, or the natural or unnatural isomers thereof, of at least one organic base, as well as compositions and uses thereof. The compounds of the invention show a long lasting stability as well as a peculiarly high water-solubility.

  本发明涉及叶酸、其组合物和用途；具体而言，本发明描述了一种结晶或非晶化合物，该化合物是一种取代或未取代的叶酸或还原叶酸，或其至少一种有机碱的天然或非天然异构体，以及其组合物和用途。本发明的化合物表现出长期稳定性以及异常高的水溶性。
• [EN] STABLE PHARMACEUTICAL COMPOSITION CONTAINING FOLATES<br/>[FR] COMPOSITION PHARMACEUTIQUE STABLE CONTENANT DES FOLATES
  申请人：APROFOL AG

  公开号：WO2014177274A1

  公开（公告）日：2014-11-06

  The administration of leucovorin as well as other active, reduced folates are useful as an antidote to drugs which act as folic acid antagonists and in combination chemotherapy with 5-FU. The most often used calcium salts of the folates have a low solubility in water and form almost insoluble degradation products. Therefore aqueous solutions are unstable and precipitates are resulting. Precipitates in injectable products present an unacceptable safety risk to patients. Stable high strength pharmaceutical aqueous compositions are formed containing calcium salts, magnesium or zinc salts of the reduced folates leucovorin, (6R,S)-tetrahydrofolic acid, (6S)-tetrahydrofolic acid, 5,10- methylene-(6R,S)-tetrahydrofolate, 5,10-methylene-(6R)-tetrahydrofolate, 5- methyl-(6R,S)-tetrahydrofolate or 5-methyl-(6S)-tetrahydrofolate and one or more of the compounds sodium gluconate, potassium gluconate, glycerophosphate disodium salt or glycerophosphate dipotassium salt.

  亚叶酸及其他活性的、还原的叶酸的使用作为对作为叶酸拮抗剂的药物的解毒剂以及与5-氟尿嘧啶联合化疗是有用的。叶酸的钙盐通常在水中溶解度较低，并形成几乎不溶解的降解产物。因此，水溶液是不稳定的，会产生沉淀。注射产品中的沉淀对患者构成不可接受的安全风险。形成了稳定的高强度药用水性配方，其中包含亚叶酸、(6R,S)-四氢叶酸、(6S)-四氢叶酸、5,10-亚甲基-(6R,S)-四氢叶酸、5,10-亚甲基-(6R)-四氢叶酸、5-甲基-(6R,S)-四氢叶酸或5-甲基-(6S)-四氢叶酸的钙盐、镁盐或锌盐以及一种或多种化合物，如葡萄糖酸钠、葡萄糖酸钾、二钠甘油磷酸盐或二钾甘油磷酸盐。
• Stable high dose pharmaceutical composition containing folates
  申请人：Aprofol AG

  公开号：EP2799061A1

  公开（公告）日：2014-11-05

  The administration of leucovorin and levoleucovorin as well as other active, reduced folates are useful as an antidote to drugs which act as folic acid antagonists and in combination chemotherapy with 5-FU. The most often used calcium salts of the folates have a low solubility in water. Therefore aqueous solutions are unstable and precipitates are resulting. Precipitates in injectable products present an unacceptable risk to patients. Stable high strength pharmaceutical aqueous compositions containing calcium salts, magnesium or zinc salts of the reduced folates leucovorin, levoleucovorin, (6R,S)-tetrahydrofolic acid, (6S)-tetrahydrofolic acid, 5,10-methylene-(6R,S)-tetrahydrofolate, 5,10-methylene-(6R)-tetrahydrofolate, 5-methyl-(6R,S)-tetrahydrofolate or 5-methyl-(6S)-tetrahydrofolate and one or more of the compounds sodium gluconate, potassium gluconate, magnesium gluconate, calcium gluconate, sodium lactate, potassium lactate, magnesium lactate, calcium lactate, glycerophosphate disodium salt, glycerophosphate dipotassium salt glycerophosphate calcium salt or glycerophosphate magnesium salt are disclosed.

  白斑葉酸和左旋白斑葉酸的使用，以及其他有效的还原型叶酸，可作为拮抗叶酸类药物的解毒剂，以及与5-FU联合化疗。最常用的叶酸钙盐在水中的溶解度较低。因此，水溶液不稳定，会产生沉淀。注射产品中的沉淀对患者构成不可接受的风险。本发明揭示了稳定的高强度制药水溶液组合物，其中包含白斑葉酸、左旋白斑葉酸、(6R,S)-四氢叶酸、(6S)-四氢叶酸、5,10-亚甲基-(6R,S)-四氢叶酸、5,10-亚甲基-(6R)-四氢叶酸、5-甲基-(6R,S)-四氢叶酸或5-甲基-(6S)-四氢叶酸的钙盐、镁盐或锌盐，以及一个或多个化合物，如葡萄糖酸钠、葡萄糖酸钾、葡萄糖酸镁、葡萄糖酸钙、乳酸钠、乳酸钾、乳酸镁、乳酸钙、二钠磷酸甘油酸盐、二钾磷酸甘油酸盐、磷酸二钙甘油酸盐或磷酸二镁甘油酸盐。
• Stable crystalline (6R) -tetrahydrofolic acid
  申请人：EPROVA AKTIENGESELLSCGAFT

  公开号：US20010002398A1

  公开（公告）日：2001-05-31

  Pure and extremely stable crystalline (6S)- and (6R)-tetrahydrofolic acids, absolutely inert even when exposed to air and elevated temperature without stabilizers being added, are prepared by a crystallization process at a pH of ≧3.5 for the preparation of crystalline (6S)-tetrahydrofolic acid and at a pH of ≧2 for the preparation of crystalline (6R)-tetrahydrofolic acid.

  纯净且极其稳定的结晶（6S）-和（6R）-四氢叶酸，即使在没有添加稳定剂的情况下暴露在空气和高温下，也是绝对惰性的。通过在pH为≥3.5的条件下制备结晶（6S）-四氢叶酸和在pH为≥2的条件下制备结晶（6R）-四氢叶酸的结晶过程来制备。
• Compositions and methods for treating an arthritic condition
  申请人：——

  公开号：US20020094970A1

  公开（公告）日：2002-07-18

  The present invention features compositions and methods for the treatment of an arthritic condition. The compositions contain a reduced folate compound and a cobalamin compound.

  本发明的特点是提供了一种治疗关节炎的组合物和方法。该组合物包含一种还原型叶酸化合物和一种钴胺素化合物。