2,4-diamino-5-methyl-6-[(3,4,5-trimethoxyanilino)methyl]quinazoline monoacetate | 52128-36-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: 2,4-diamino-5-methyl-6-[(3,4,5-trimethoxyanilino)methyl]quinazoline monoacetate
• 英文别名: trimetrexate acetate；Trimetrexate monoacetate；acetic acid;5-methyl-6-[(3,4,5-trimethoxyanilino)methyl]quinazoline-2,4-diamine
• CAS: 52128-36-6
• 化学式: C₂H₄O₂*C₁₉H₂₃N₅O₃
• 分子量: 429.476
• InChiKey: LZAHAWHPLGBAQD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.83
• 重原子数：
  31
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  155
• 氢给体数：
  4
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  溶剂黄146 、 3,4,5-三甲氧基苯胺 、 2,4-二氨基-5-甲基喹唑啉-6-甲腈 在 镍 氢气 作用下， 28.0 ℃ 、344.73 kPa 条件下， 反应 22.0h， 以26%的产率得到2,4-diamino-5-methyl-6-[(3,4,5-trimethoxyanilino)methyl]quinazoline monoacetate
  参考文献：
  名称：

  Folate antagonists. 20. Synthesis and antitumor and antimalarial properties of trimetrexate and related 6-[(phenylamino)methyl]-2,4-quinazolinediamines

  摘要：

  A series of 6-[(arylamino)methyl]-2,4-quinazolinediamines have been prepared by catalytic hydrogenation of the requisite 2,4-diamino-6-quinazolinecarbonitriles in the presence of the appropriate benzenamine. Formylation, acetylation, and nitrosation provided N omega derivatives of these compounds. A variety of the compounds exhibited potent antimalarial, antibacterial, and antitumor activity. In particular, 5-methyl-6-[[(3,4,5-trimethoxyphenyl)-amino]methyl]-2, 4-quinazolinediamine (trimetrexate, 15) has shown a broad spectrum of antitumor effects and is undergoing preclinical toxicology evaluation prior to trial in man.

  DOI：

  10.1021/jm00366a018

文献信息

• Thermally stable trimetrexates and processes for producing the same
  申请人：MedImmune Oncology, Inc.

  公开号：US20030199694A1

  公开（公告）日：2003-10-23

  The present invention provides for thermally stable forms of 2,4-diamino-5-methyl-6-[(3,4,5-trimethoxyanilino)methyl] quinazoline, or trimetrexate. A crystalline 2,4-diamino-5-methyl-6-[(3,4,5-trimethoxyanilino)methyl] quinazoline monohydrate, or trimetrexate monohydrate, belonging to the space group Poverscore (1)}(#2) and having a triclinic cell with dimensions of about a=7.699 Å, b=9.606 Å and c=13.012 Å is disclosed. A novel Schiff base compound, 2,4-diamino-5-methyl-6-[(3,4,5-trimethoxyphenylimino)-methinyl]quinazoline, is also disclosed. The present invention further provides novel methods of producing stable trimetrexate free base compounds, including crystalline trimetrexate monohydrate. The crystalline monohydrate form provides increased stability over the anhydrous form.

  本发明提供了2,4-二氨基-5-甲基-6-[(3,4,5-三甲氧基苯胺基)甲基]喹唑啉或三甲嘧啶的热稳定形式。其中揭示了属于空间群Poverscore (1)}(#2)、具有三斜晶胞尺寸为a≈7.699Å、b≈9.606Å和c≈13.012Å的2,4-二氨基-5-甲基-6-[(3,4,5-三甲氧基苯胺基)甲基]喹唑啉单水合物或三甲嘧啶单水合物的晶体。此外，本发明还揭示了一种新的席夫碱化合物，即2,4-二氨基-5-甲基-6-[(3,4,5-三甲氧基苯亚胺基)-甲基炔基]喹唑啉。本发明还提供了新的稳定三甲嘧啶游离基化合物的制备方法，包括晶体三甲嘧啶单水合物。晶体单水合物形式比无水形式具有更高的稳定性。
• Tremextrexate derivatives and pharmaceutical compositions comprising the same
  申请人：MedImmune Oncology, Inc.

  公开号：US20020107393A1

  公开（公告）日：2002-08-08

  The present invention provides for thermally stable forms of 2,4-diamino-5-methyl-6-[(3,4,5-trimethoxyanilino)methyl] quinazoline, or trimetrexate. A crystalline 2,4-diamino-5-methyl-6-[(3,4,5-trimethoxyanilino)methyl] quinazoline monohydrate, or trimetrexate monohydrate, belonging to the space group Poverscore (1)} (#2) and having a triclinic cell with dimensions of about a=7.699 Å, b=9.606 Å and c=13.012 Å is disclosed. A novel Schiff base compound, 2,4-diamino-5-methyl-6-[(3,4,5-trimethoxyphenylimino)-methinyl]quinazoline, is also disclosed. The present invention further provides novel methods of producing stable trimetrexate free base compounds, including crystalline trimetrexate monohydrate. The crystalline monohydrate form provides increased stability over the anhydrous form.

  本发明提供了2,4-二氨基-5-甲基-6-[(3,4,5-三甲氧基苯胺基)甲基]喹嗪或三甲嘧啶的热稳定形式。本发明揭示了属于空间群P1（#2）的三斜晶胞，尺寸约为a=7.699Å，b=9.606Å和c=13.012Å的2,4-二氨基-5-甲基-6-[(3,4,5-三甲氧基苯胺基)甲基]喹嗪单水合物或三甲嘧啶单水合物。本发明还揭示了一种新的席夫碱化合物，2,4-二氨基-5-甲基-6-[(3,4,5-三甲氧基苯亚胺基)-甲烯基]喹嗪。本发明还提供了生产稳定的三甲嘧啶游离碱化合物的新方法，包括结晶三甲嘧啶单水合物。晶体单水合物形式提供了比无水形式更高的稳定性。
• Process for preparing 5,6-substituted-2,4-quinazolinediamines and intermediates
  申请人：WARNER-LAMBERT COMPANY

  公开号：EP0253396A2

  公开（公告）日：1988-01-20

  An improved process for the preparation of 6-substituted-5-­alkyl-2,4-quinazolinediamines, useful in the production of trimetrexate and similar antifolate agents, together with several novel intermediates are disclosed.

  本发明公开了一种改进的 6-取代-5-烷基-2,4-喹唑啉二胺制备工艺以及几种新型中间体，该工艺可用于生产曲美曲塞特和类似的抗叶酸制剂。
• Water-soluble salts of 2,4-diamino-5-methyl-6-((3,4,5-trimethoxyanilino)methyl)quinazoline, compositions containing such salts and the production of such salts
  申请人：WARNER-LAMBERT COMPANY

  公开号：EP0051415B1

  公开（公告）日：1984-11-14
• EP0804197A4
  申请人：——

  公开号：EP0804197A4

  公开（公告）日：1998-09-30