2-[[4-[2-(2-氨基-4-氧代-1H-蝶啶-6-基)乙基氨基]苯甲酰基]氨基]戊烷二酸 | 3566-25-4

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 中文名称: 2-[[4-[2-(2-氨基-4-氧代-1H-蝶啶-6-基)乙基氨基]苯甲酰基]氨基]戊烷二酸
• 英文名称: Homofolsaeure
• 英文别名: N-{4-[2-(2-amino-4-oxo-3,4-dihydro-pteridin-6-yl)-ethylamino]-benzoyl}-glutamic acid；Homofolic acid；(2S)-2-[[4-[2-(2-amino-4-oxo-3H-pteridin-6-yl)ethylamino]benzoyl]amino]pentanedioic acid
• CAS: 3566-25-4
• 化学式: C₂₀H₂₁N₇O₆
• 分子量: 455.43
• InChiKey: QXARTGUOGAZGKO-ZDUSSCGKSA-N

物化性质

• 沸点：
  561.92°C (rough estimate)
• 密度：
  1.4383 (rough estimate)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.6
• 重原子数：
  33
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  209
• 氢给体数：
  6
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  、 2-[[4-[2-(2-氨基-4-氧代-1H-蝶啶-6-基)乙基氨基]苯甲酰基]氨基]戊烷二酸 、 氢气 在 氧化铂 作用下， 生成 Tetrahydrohomofolate
  参考文献：
  名称：

  Production of N.sup.5 -methyltetrahydrohomofolic acid and related

  摘要：

  N.sup.5-甲基四氢叶酸和其碱金属盐的制备是从同型叶酸（HFA）起始物质开始，通过在氢气下在暗中使用铂氧化物催化还原，产生四氢同型叶酸（THHF），然后立即将此产物与甲醛反应，生成5,11-甲烯基四氢同型叶酸，并通过与硼氢化钠不隔离的还原甲烯中间体，以得到所需的5-甲基四氢同型叶酸二钠盐形式。在pH约为3.8的乙酸下沉淀副产物，并在约3°C至10°C的温度下冷藏产物滤液过夜以回收5-甲基产物。含有5-甲基四氢同型叶酸（5-MeTHHF）的滤液经过活性炭处理，浓缩至油状物，然后使用绝对乙醇沉淀5-甲基产物。5,11-甲烯基四氢叶酸可以单独回收，并且在第二次反应中，通过与甲酸反应形成了另一种名为5,11-甲烯基的产物。这些产品显示出比叶酸类似物更高的稳定性，并在癌症和白血病治疗中表现出生物学前景，作为抗叶酸类药物，特别针对小鼠L1210-FR8肿瘤。

  公开号：

  US03983118A1

文献信息

• Process For The Preparation Of Optically Pure Tetrahydropterins And Derivatives, And Specifically Of Optically Pure Tetrahydrofolic Acid And Derivatives Thereof, By Stereospecific Hydrogenation
  申请人：MULLER Hans Rudolf

  公开号：US20080306263A1

  公开（公告）日：2008-12-11

  Process for the preparation of tetrahydropterin and tetrahydropterin derivatives by hydrogenating pterin and pterin derivatives with hydrogen in the presence of a hydrogenating catalyst, in which the hydrogenation is carried out in a polar reaction medium and metal complexes that are soluble in the reaction medium are employed as the hydrogenation catalysts. The process is suited to the hydrogenation, particularly asymmetric hydrogenation, of folic acid, folio acid salts, folio acid esters, folio acid ester salts or dihydroforms thereof, with the proviso that in the event of using folic acid, carboxylic acid salts thereof or dihydroforms thereof the reaction medium is aqueous, and in the event of using folic acid esters, folic acid ester salts or dihydroforms thereof the reaction medium is an alcohol. The process opens up straightforward access to achiral and chiral pterin derivatives.

  通过在存在氢化催化剂的情况下，用氢气氢化葉酸和葉酸衍生物制备四氢生物葉酸和四氢生物葉酸衍生物的过程，其中氢化是在极性反应介质中进行的，并且可溶于反应介质的金属配合物被用作氢化催化剂。该过程适用于葉酸、葉酸盐、葉酸酯、葉酸酯盐或其二氢形式的氢化，特别是不对称氢化，但若使用葉酸、其羧酸盐或二氢形式，则反应介质为水，若使用葉酸酯、葉酸酯盐或其二氢形式，则反应介质为醇。该过程为得到无手性和手性葉酸衍生物提供了直接途径。
• Single stage reduction and formylation of folic or homofolic acid
  申请人：DANA FARBER CANCER INSTITUTE

  公开号：EP0189990A2

  公开（公告）日：1986-08-06

  Folic or homofolic acid is converted to the corresponding N -formyl-5,6,7,8-tetrahydrofolic or-homofolic acid by reaction in solution in excess formic acid at 0°-15°C with a secondary amine complex of borane.

  叶酸或高叶酸在 0°-15°C、过量甲酸溶液中与硼烷的仲胺络合物反应，可转化为相应的 N-甲酰基-5,6,7,8-四氢叶酸或高叶酸。
• Glutamic acid derivatives, processes and intermediates for their preparation and pharmaceutical formulations containing them
  申请人：THE WELLCOME FOUNDATION LIMITED

  公开号：EP0268377A2

  公开（公告）日：1988-05-25

  The present invention provides a compound of formula (I): wherein R¹ is hydrogen, C1-4 alkyl, acetyl or formyl; R² and R³ are the same or different and are hydrogen or C1-4 alkyl; R⁴ is NR¹¹R¹²; R¹¹, R¹², R⁵ and R⁶ are the same or different and are hydrogen, C1-4 alkyl or C1-12 acyl; R⁷, R⁸, R⁹ and R¹⁰ are the same or different and are hydrogen, halo, C1-4 haloalkyl, C1-4 alkyl and C1-4 alkoxy; and n is 2, 3, 4 or 5; m is o or an integer from 1 to 6; or a salt thereof, methods for the preparation of the compounds of the formula (I), intermediates in their preparations, pharmaceutical formulations containing them, and their use in the treatment of tumours.

  本发明提供了一种式(I)化合物： 其中 R¹ 是氢、C1-4 烷基、乙酰基或甲酰基；R² 和 R³ 相同或不同，并且是氢或 C1-4 烷基；R⁴ 是 NR¹R¹²；R¹¹、R¹²、R⁵和R⁶相同或不同，是氢、C1-4 烷基或 C1-12酰基；R⁷、R⁸、R⁹和R¹⁰相同或不同，是氢、卤代、C1-4 卤代烷基、C1-4 烷基和 C1-4 烷氧基；n 是 2、3、4 或 5；m 是 o 或 1 至 6 的整数；或其盐、式 (I) 化合物的制备方法、其制备过程中的中间体、含有它们的药物制剂，以及它们在治疗肿瘤中的用途。
• Sustained release formulation of methotrexate as a disease-modifying antirheumatic drug (DMARD) and an anti-cancer agent
  申请人：PACIRA PHARMACEUTICALS, INC.

  公开号：US10028911B2

  公开（公告）日：2018-07-24

  Disclosed is are formulations comprising a multivesicular liposome and MTX, the administration of which results in a Cmax of MTX between 5% and 50% of the Cmax of an immediate release dosage form of MTX, the duration of which lasts from about 1 to about 30 days. Also disclosed are methods of treating autoimmune diseases and cancer by administering these formulations of MTX.

  公开了包含多囊脂质体和MTX的制剂，给药后MTX的Cmax为MTX速释剂型Cmax的5%至50%，持续时间约为1至30天。还公开了通过施用这些MTX制剂治疗自身免疫性疾病和癌症的方法。
• Process for producing cell having high productivity of protein and process for preparing protein by using the cell
  申请人：KANEGAFUCHI KAGAKU KOGYO KABUSHIKI KAISHA

  公开号：EP0223230B1

  公开（公告）日：1991-10-23