3-(2-氯乙基)-3,4-二氢-4-氧代吡唑并[5,1-d]-1,2,3,5-四嗪-8-甲酰胺 | 90521-23-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 中文名称: 3-(2-氯乙基)-3,4-二氢-4-氧代吡唑并[5,1-d]-1,2,3,5-四嗪-8-甲酰胺
• 中文别名: 二苯并呋喃,七溴氯-
• 英文名称: 8-carbamoyl-3-(2-chloroethyl)pyrazolo<5,1-d>-1,2,3,5-tetrazin-4(3H)-one
• 英文别名: 3-(2-chloroethyl)-3,4-dihydro-4-oxopyrazolo<5,1-d>-1,2,3,5-tetrazine-8-carboxamide；Mitozolomide；3-(2-chloroethyl)-4-oxopyrazolo[5,1-d]-1,2,3,5-tetrazine-8-carboxamide；3-(2-Chloroethyl)-3,4-dihydro-4-oxopyrazolo(5,1-d)-1,2,3,5-tetrazine-8-carboxamide；3-(2-chloroethyl)-4-oxopyrazolo[5,1-d][1,2,3,5]tetrazine-8-carboxamide
• CAS: 90521-23-6
• 化学式: C₇H₇ClN₆O₂
• 分子量: 242.625
• InChiKey: GCOAJPQTYKOBSK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.1
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  106
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  聚合甲醛 、 3-(2-氯乙基)-3,4-二氢-4-氧代吡唑并[5,1-d]-1,2,3,5-四嗪-8-甲酰胺 在 硫酸 作用下， 反应 5.0h， 以40%的产率得到N,N'-Bis[3,4-dihydro-4-oxo-3-(2-chloroethyl)imidazo[5,1-d][1,2,3,5]tetrazin-8-ylcarbonyl]diaminomethane
  参考文献：
  名称：

  Antitumour imidazotetrazines. Part 39. Synthesis of bis(imidazotetrazine)s with saturated spacer groups

  摘要：

  双(咪唑四嗪) (16) 的结构与抗肿瘤药物米唑仑 (1a) 和替莫唑胺 (1b) 相关，但通过咪唑[5,1-d][1,2,3,5]四嗪环系的N(3)–N(3′)原子相连，由5-氮杂咪唑-4-羧酰胺 (8) 和二异氰酸酯 (15) 反应制备而成。含/不含硫和氧杂原子的多亚甲基连接体的存在并未显著影响与未连接的咪唑四嗪米唑仑和替莫唑胺特征相关的酸稳定性、碱催化分解、抗肿瘤活性或DNA碱基烷基化偏好。

  DOI：

  10.1039/b005652i
• 作为产物：
  描述：

  氯乙基异氰酸酯 、 5-重氮咪唑-4-甲酰胺 以 乙酸乙酯 为溶剂， 反应 168.0h， 以20%的产率得到3-(2-氯乙基)-3,4-二氢-4-氧代吡唑并[5,1-d]-1,2,3,5-四嗪-8-甲酰胺
  参考文献：
  名称：

  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

  摘要：

  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.

  DOI：

  10.1021/jm00385a018

文献信息

• 3-Haloethyl-4-oxopyrazolo (5,1-d)-1,2,3,5-tetrazine-8-carboxamide and process for their production and use
  申请人：WARNER-LAMBERT COMPANY

  公开号：EP0127028A2

  公开（公告）日：1984-12-05

  The title compounds are provided as well as a method for their production, pharmaceutical compositions comprising the compounds, and a method of treatment using the compounds in dosage form. Compounds of the invention have pharmacological properties and are useful antimicrobial agents and antileukemic agents.

  本发明提供了标题化合物及其生产方法、包含这些化合物的药物组合物以及使用这些化合物进行治疗的方法。 本发明的化合物具有药理特性，是有用的抗微生物剂和抗白血病剂。
• Pyrazole derivatives. 5. Synthesis and antineoplastic activity of 3-(2-chloroethyl)-3,4-dihydro-4-oxopyrazolo[5,1-d]-1,2,3,5-tetrazine-8-carboxamide and related compounds
  作者：C. C. Cheng、Edward F. Elslager、Leslie M. Werbel、Wilbur R. Leopold

  DOI：10.1021/jm00158a041

  日期：1986.8

  Two pyrazolotetrazine derivatives were synthesized as the analogous prodrugs of the light-sensitive antineoplastic agents dacarbazine and BIC. Both the pyrazole derivatives are stable under ordinary light illumination. Biological evaluation of these pyrazoles revealed that the compound containing a 2-chloroethyl function (6a) demonstrated good antineoplastic activity in experimental animals, but the one containing a methyl function (6b) was inactive. The inactivity of compound 6b may suggest that compound 6a and related imidazotetrazines may simply act as biological alkylating agents per se rather than as prodrugs. The information could also imply that the postulated dealkylation mechanism for the triazene derivatives should be reexamined.
• CHENG, CHIA-CHUNG
  作者：CHENG, CHIA-CHUNG

  DOI：——

  日期：——
• CHENG, CHIA, C.
  作者：CHENG, CHIA, C.

  DOI：——

  日期：——
• CHENG C. C.; ELSLAGER E. F.; WERBEL L. M.; PRIEBE S. R.; LEOPOLD W. R., J. MED. CHEM., 29,(1986) N 8, 1544-1547
  作者：CHENG C. C.、 ELSLAGER E. F.、 WERBEL L. M.、 PRIEBE S. R.、 LEOPOLD W. R.

  DOI：——

  日期：——