3-(2-氯乙基)-N-甲基-4-氧代-3,4-二氢咪唑并[5,1-d][1,2,3,5]四嗪-8-甲酰胺 | 85622-96-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑四嗪类
• 中文名称: 3-(2-氯乙基)-N-甲基-4-氧代-3,4-二氢咪唑并[5,1-d][1,2,3,5]四嗪-8-甲酰胺
• 英文名称: 3-(2-chloroethyl)-N-methyl-4-oxoimidazo<5,1-d>-1,2,3,5-tetrazine-8-carboxamide
• 英文别名: 3-(2-chloroethyl)-8-methylcarbamoyl-[3H]-imidazo[5,1-d]-1,2,3,5-tetrazin-4-one；8-(N-Methyl)mitozolomide；3-(2-chloroethyl)-N-methyl-4-oxoimidazo[5,1-d][1,2,3,5]tetrazine-8-carboxamide
• CAS: 85622-96-4
• 化学式: C₈H₉ClN₆O₂
• 分子量: 256.651
• InChiKey: ZIBAAYKCNSFPRL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.1
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  92
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  benzyl 3-(2-chloroethyl)-3H-4-oxoimidazo<5,1-d>-1,2,3,5-tetrazine-8-carboxylate 在 palladium on activated charcoal 氯化亚砜 、 氢气 、 N,N-二甲基甲酰胺 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 3.0h， 生成 3-(2-氯乙基)-N-甲基-4-氧代-3,4-二氢咪唑并[5,1-d][1,2,3,5]四嗪-8-甲酰胺
  参考文献：
  名称：

  Antitumor imidazotetrazines. 20. Preparation of the 8-acid derivative of mitozolomide and its utility in the preparation of active antitumor agents

  摘要：

  The preparation of 3-(2-chlorethyl)-4-oxo-3H-imidazo[5,1-d]-1,2,3,5- tetrazine-8-carboxylic acid, a key derivative of mitozolomide in our exploration of the structure-activity relationships of this class of antitumor agents, is described. The facile conversion to the 8-carbonyl chloride gave a derivative that reacted preferentially with nucleophiles at the 8-position rather than at the reactive 4-oxo group, allowing the preparation of a wide range of ester, thioester, amide (including an amide derived from an amino acid), hydroxamic acid, hydrazide and sulfoximide, azide and diazoacetyl derivatives. The in vivo activity is presented of a range of these compounds against TLX5 lymphoma and L1210 leukemia cell lines.

  DOI：

  10.1021/jm00167a018

文献信息

• METHODS AND COMPOSITIONS FOR TREATING CANCER
  申请人：Kolhe Parag

  公开号：US20100143340A1

  公开（公告）日：2010-06-10

  The present invention provides methods for preventing or treating a medical disorder in a subject comprising administering to the subject an effective amount of a stable pharmaceutical formulation comprising an antibody or antigen-binding fragment thereof.

  本发明提供了一种预防或治疗受试者医疗障碍的方法，包括向受试者投与一种包含抗体或其抗原结合片段的稳定药物制剂的有效量。
• Treatment of brain and central nervous system tumors
  申请人：KADMON CORPORATION LLC

  公开号：US10080752B2

  公开（公告）日：2018-09-25

  The present invention provides methods for treating tumors of the brain by administering the compounds of the Formula A and particularly N-(3,4-dichloro-2-fluorophenyl)-7-([(3aR,6aS)-2-methyloctahydrocyclopenta[c]pyrrol-5-yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine, or a pharmaceutically acceptable salt thereof, to a subject in need of such treatment. In the methods of the invention, the compounds disclosed herein were surprisingly found to cross the blood brain barrier. The method of the present invention further relates to the treatment of cancers of any type potentially responding to EGFR, HER2, VEGFR2, or Src family kinase inhibitors and that are found in the brain.

  本发明提供了治疗脑肿瘤的方法，通过向需要治疗的受试者施用式A化合物，特别是N-(3,4-二氯-2-氟苯基)-7-([(3aR,6aS)-2-甲基八氢环戊并[c]吡咯-5-基]甲基}氧基)-6-(甲氧基)喹唑啉-4-胺或其药学上可接受的盐。在本发明的方法中，令人惊讶地发现本发明公开的化合物可以穿过血脑屏障。本发明的方法进一步涉及对表皮生长因子受体（EGFR）、HER2、血管内皮生长因子受体（VEGFR2）或Src家族激酶抑制剂有潜在反应的任何类型癌症的治疗，这些癌症在大脑中发现。
• Platinum therapeutic combinations
  申请人：Zong Chen

  公开号：US20060205810A1

  公开（公告）日：2006-09-14

  The present invention provides combination compositions comprising Pt based compounds, including satraplatin, along with another chemotherapeutic agent such as temozolomide or lonafarnib. The combinations are useful for the prevention or treatment of cancer. Method of using the combinations to treat or prevent cancer are also provided

  本发明提供了由铂类化合物（包括沙拉铂）与另一种化疗药物（如替莫唑胺或洛纳法尼）组成的组合物。这些组合物可用于预防或治疗癌症。还提供了使用这些组合物治疗或预防癌症的方法
• Antitumor imidazotetrazines. 14. Synthesis and antitumor activity of 6- and 8-substituted imidazo[5,1-d]-1,2,3,5-tetrazinones and 8-substituted pyrazolo[5,1-d]-1,2,3,5-tetrazinones
  作者：Edward Lunt、Christopher G. Newton、Christopher Smith、Graham P. Stevens、Malcolm F. G. Stevens、Colin G. Straw、Roger J. A. Walsh、Peter J. Warren、Christian Fizames

  DOI：10.1021/jm00385a018

  日期：1987.2

  The systematic variation of the potent antitumor agent mitozolomide (1) is extended to cover alteration of substituents at positions 6 and 8 and to change the imidazo[5,1-d]-1,2,3,5-tetrazinone (1) skeleton to the isomeric pyrazolo-[5,1-d]-1,2,3,5-tetrazinone (17) skeleton. The series of eight 6-alkyl and 6-aralkyl derivatives of 1 showed optimal antitumor activity when the group was small or linear, but activity diminished as size and branching of this substituent increased. This may reflect altered transport characteristics, or failure of the enlarged derivatives to fit a binding site, or possibly a reduced tendency for the derivatives having bulky groups at position 6 to hydrolytically generate the putatively active triazenes (21). Testing of 14 derivatives of 1 differently substituted at position 8 revealed a complex structure-activity relationship, with good antitumor activity obtained for carbamoyl and sulfamoyl groups bearing small substituents. The 8-methylsulfonyl compound had noteworthy activity, but the 8-cyano, 8-nitro, and 8-phenyl derivatives were devoid of useful antitumor activity in these tests. From the limited number of pyrazolotetrazinones (17) reported here, it is suggested that the same conclusions as regards activity also hold true for this ring system.
• LUNT E.; NEWTON CH. G.; SMITH CH.; STEVENS G. P.; STEVENS M. F. G.; STRAW+, J. MED. CHEM., 30,(1987) N 2, 357-366
  作者：LUNT E.、 NEWTON CH. G.、 SMITH CH.、 STEVENS G. P.、 STEVENS M. F. G.、 STRAW+

  DOI：——

  日期：——