(9ci)-5-氨基-n-甲基-1H-咪唑-4-羧酰胺 | 53525-66-9

• 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: (9ci)-5-氨基-n-甲基-1H-咪唑-4-羧酰胺
• 英文名称: 4-amino-5-(N-methylcarbamoyl)imidazole
• 英文别名: 5(4)-Aminoimidazol-4(5)-(N-methyl)-carboxamid；5-amino-1(3)H-imidazole-4-carboxylic acid methylamide；5-amino-4-methylcarbamoylimidazole；4-amino-N-methyl-1H-imidazole-5-carboxamide
• CAS: 53525-66-9
• 化学式: C₅H₈N₄O
• mdl: MFCD20542017
• 分子量: 140.145
• InChiKey: KDDMHNRJLWGNAE-UHFFFAOYSA-N

物化性质

• 熔点：
  217 °C (decomp)(Solv: ethanol (64-17-5))
• 沸点：
  549.5±35.0 °C(Predicted)
• 密度：
  1.352±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.1
• 重原子数：
  10
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  83.8
• 氢给体数：
  3
• 氢受体数：
  3

安全信息

• 海关编码：
  2934999090

反应信息

• 作为反应物：
  描述：

  (9ci)-5-氨基-n-甲基-1H-咪唑-4-羧酰胺 在 4-二甲氨基吡啶 、 sodium hydroxide 、 一水合肼 、 三乙胺 作用下， 以 1,4-二氧六环 、 吡啶 、 乙醇 、 N,N-二甲基甲酰胺 、 丙酮 为溶剂， 反应 63.5h， 生成 9-(2-Benzoxyethoxymethyl)-1-methylguanine
  参考文献：
  名称：

  嘌呤和咪唑核苷的无环类似物

  摘要：

  的1-和3-（2-羟基乙氧基甲基）咪唑（羟基被保护的衍生物4,5,7-10）已经从5-氨基-4- carbamoylimidazoles（制备2）。将受保护的衍生物转化为咪唑核苷的无环类似物（6）或进行各种环化反应，生成9-（2-羟基-乙氧基甲基）取代的2-甲基-，2-苯基-和2-氮杂泛黄嘌呤（18,13和分别为20和1-甲基鸟嘌呤（28）。为了将结构分配给异构的咪唑和嘌呤衍生物，已使用13 C化学位移。

  DOI：

  10.1002/jhet.5570190104
• 作为产物：
  描述：

  5-Nitro-imidazol-4-(N-methyl)-carboxamid 在 platinum(IV) oxide 氢气 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 以97%的产率得到(9ci)-5-氨基-n-甲基-1H-咪唑-4-羧酰胺
  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

• Synthesis of new azolo[5,1-d][1,2,3,5]tetrazin-4-ones–analogs of antitumor agent temozolomide
  作者：E. V. Sadchikova

  DOI：10.1007/s11172-016-1522-9

  日期：2016.7

  the reactions with alkyland aryl isocyanates was studied. A number of new imidazo-and pyrazolo[5,1-d][1,2,3,5]tetrazin-4 ones were synthesized, which are analogs of temozolomide. It was shown that diazoazoles do not react with isothiocyanates under similar conditions.

  研究了 5-重氮咪唑和 5-重氮吡唑在与烷基和芳基异氰酸酯反应中的反应性。合成了许多新的咪唑并吡唑并[5,1-d][1,2,3,5]tetrazin-4，它们是替莫唑胺的类似物。结果表明，在类似条件下，重氮唑不与异硫氰酸酯反应。
• Synthesis and Pharmacological Activity of Triazole Derivatives Inhibiting Eosinophilia
  作者：Youichiro Naito、Fumihiko Akahoshi、Shinji Takeda、Takehiro Okada、Masahiko Kajii、Hiroko Nishimura、Masanori Sugiura、Chikara Fukaya、Yoshio Kagitani

  DOI：10.1021/jm9507993

  日期：1996.1.1

  In order to develop novel antiasthmatic agents based on a new mechanism of action, a series of 3-substituted 5-amino-1-[(methylamino)(thiocarbonyl)]-1H-1,2,4-triazole derivatives were synthesized and evaluated in a model in which eosinophilia was induced in the ah-way through intravenous (iv) injection of Sephadex particles on days 0, 2, and 5. After screening of several hundred derivatives, we finally identified the highly potent eosinophilia inhibitor 5-amino-3-(4-chlorophenyl)-1-[(methylamino)(thiocarbonyl)]-1H-triazole (23c, GCC-AP0341), which had ID50 values of 0.3 and 0.07 mg/kg when administered orally (os) and intraperitoneally tip), respectively. This compound showed complete inhibition of the hypersensitivity induced by ascaris inhalation at an ip dose of 1 mg/kg as well as low toxicity, with an LD(50) value of > 2.0 g/kg in mice. Extensive study of its mechanism of action revealed that 23c inhibited eosinophil survival induced by interleukin-5 (IL-5), but had little or no effect on leukotriene D-4 (LTD(4)) or platelet-activating factor (PAF)-induced responses. Taken together, these results suggest 23e as a novel candidate for the treatment of chronic asthma. Further studies are now underway.
• Synthesis and structure of new imidazo- and pyrazolo[5,1-d][1,2,3,5]thiatriazines based on the reaction of diazoazoles with acyl isothiocyanates controlled by S⋯O interaction
  作者：Elena V. Sadchikova、Vasiliy A. Bakulev、Julia O. Subbotina、Darya L. Privalova、Wim Dehaen、Kristof Van Hecke、Koen Robeyns、Luc Van Meervelt、Vladimir S. Mokrushin

  DOI：10.1016/j.tet.2013.06.062

  日期：2013.8

  5-Diazoimidazoles and 5-diazopyrazoles have been shown to react with acyl isothiocyanates yielding the imidazo- and pyrazolo[5,1-d][1,2,3,5]thiatriazines stabilized by a nonbonded S center dot center dot center dot O interaction. In contrast to acyl isothiocyanates, alkyl-, aryl-, and arylsulfonyl isothiocyanates do not react with 5-diazoazoles. The nature and the strength of stabilizing intramolecular interaction between non-bonded S and O atoms have been studied by X-ray analysis for mono crystals and DFT calculations for selected azolo[5,1-d] [1,2,3,5]thiatriazines. The interaction was described in terms of Weinhold covalence ratio factors, NBO, and AIM schemes. The reaction discovered was used to develop an efficient approach toward the new 8-substituted 4-ethoxycarbonylimino-4-benzoyl- and 4-(3,4,5,6-tetrafluorobenzoy)iminoimidazo(pyrazolo)[5,1-d][1,2,3,5]thiatriazines. (C) 2013 Elsevier Ltd. All rights reserved.
• 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：——
• 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.