5-氨基-1-丙基-1H-咪唑-4-甲酰胺 | 61507-88-8

• 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: 5-氨基-1-丙基-1H-咪唑-4-甲酰胺
• 英文名称: 5-amino-1-propyl-1H-imidazole-4-carboxamide
• 英文别名: 5-amino-1-propylimidazole-4-carboxamide；5-amino-1-n-propylimidazole-4-carboxamide
• CAS: 61507-88-8
• 化学式: C₇H₁₂N₄O
• mdl: MFCD09864516
• 分子量: 168.198
• InChiKey: LVONFJCKVYNYTJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  12
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.428
• 拓扑面积：
  86.9
• 氢给体数：
  2
• 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：

  5-氨基-1-丙基-1H-咪唑-4-甲酰胺 在 sodium hydroxide 、 copper diacetate 、 potassium carbonate 作用下， 以 甲醇 、 水 、 丙酮 为溶剂， 反应 11.0h， 生成 9-propylguanine
  参考文献：
  名称：

  A simple and efficient synthesis of 9-substituted guanines. Cyclodesulfurization of 1-substituted 5-[(thiocarbamoyl)amino]imidazole-4-carboxamides under aqueous basic conditions

  摘要：

  5-Aminoimidazole-4-carboxamide (AICA) (1a) is 1-alkylated by an improved method. The resulting 5-amino-1-alkylimidazole-4-carboxamides (1b-i) are converted to the corresponding 1-alkyl-5-[(thiocarbamoyl)-amino]imidazole-4-carboxamides (3). These compounds are ring closed under alkaline conditions to 9-substituted guanines (5) in very high yields by treatment with heavy-metal salts in aqueous sodium hydroxide, or, in somewhat lower yields, by S-oxidation with hydrogen peroxide or sodium perborate in aqueous sodium hydroxide.

  DOI：

  10.1021/jo00006a033
• 作为产物：
  描述：

  4-氨基-5-咪唑甲酰胺盐酸盐 、 溴丙烷 在 氢氧化钾 作用下， 生成 5-氨基-1-丙基-1H-咪唑-4-甲酰胺
  参考文献：
  名称：

  A simple and efficient synthesis of 9-substituted guanines. Cyclodesulfurization of 1-substituted 5-[(thiocarbamoyl)amino]imidazole-4-carboxamides under aqueous basic conditions

  摘要：

  5-Aminoimidazole-4-carboxamide (AICA) (1a) is 1-alkylated by an improved method. The resulting 5-amino-1-alkylimidazole-4-carboxamides (1b-i) are converted to the corresponding 1-alkyl-5-[(thiocarbamoyl)-amino]imidazole-4-carboxamides (3). These compounds are ring closed under alkaline conditions to 9-substituted guanines (5) in very high yields by treatment with heavy-metal salts in aqueous sodium hydroxide, or, in somewhat lower yields, by S-oxidation with hydrogen peroxide or sodium perborate in aqueous sodium hydroxide.

  DOI：

  10.1021/jo00006a033

文献信息

• Comparison of different heterocyclic scaffolds as substrate analog PDE5 inhibitors
  作者：Helmut Haning、Ulrich Niewöhner、Thomas Schenke、Thomas Lampe、Alexander Hillisch、Erwin Bischoff

  DOI：10.1016/j.bmcl.2005.05.090

  日期：2005.9

  Several different heterocyclic systems were compared as PDE5 inhibitor scaffolds. In addition to the known 3H-imidazo[5,1-f][1,2,4]triazin-4-ones and pyrazolopyrimidinones, isomeric imidazo[1,5-a][1,3,5]triazin-4(3H)-ones were also shown to be potent and selective PDE inhibitor scaffolds with in vivo activity. SAR trends were elucidated for sulfonamide derivatives with generality across different scaffolds

  比较了几种不同的杂环系统作为PDE5抑制剂支架。除了已知的3H-咪唑并[5,1-f] [1,2,4]三嗪-4-酮和吡唑并吡喃二酮外，咪唑并[1,5-a] [1,3,5]三嗪-4（ 3H）-一也被证明是具有体内活性的有效的和选择性的PDE抑制剂支架。阐明了在不同支架上具有普遍性的磺酰胺衍生物的SAR趋势。
• Purinone antianginal agents
  申请人：Pfizer Inc

  公开号：US05734053A1

  公开（公告）日：1998-03-31

  ##STR1## Compounds of formula (I), and pharmaceutically acceptable salts thereof, wherein R.sup.1 is C.sub.1 -C.sub.4 alkyl; R.sup.2 is C.sub.2 -C.sub.4 alkyl; R.sup.3 is H or SO.sub.2 NR.sup.4 R.sup.5 ; R.sup.4 and R.sup.5 together with the nitrogen atom to which they are attached form a pyrrolidino, piperidino, morpholino or 4-N-(R.sup.6)-1-piperazinyl group; and R.sup.6 is H or C.sub.1 -C.sub.3 alkyl; are selective cGMP PDE inhibitors useful in the treatment of, inter alia, cardiovascular disorders such as angina, hypertension, heart failure and atherosclerosis.

  公式（I）的化合物及其药用盐，其中R.sup.1为C.sub.1-C.sub.4烷基；R.sup.2为C.sub.2-C.sub.4烷基；R.sup.3为H或SO.sub.2NR.sup.4R.sup.5；R.sup.4和R.sup.5与它们连接的氮原子一起形成吡咯啉基、哌啶基、吗啉基或4-N-(R.sup.6)-1-哌嗪基；R.sup.6为H或C.sub.1-C.sub.3烷基；是选择性cGMP PDE抑制剂，可用于治疗心血管疾病，如心绞痛、高血压、心力衰竭和动脉粥样硬化等。
• [EN] A PROCESS FOR THE PREPARATION OF 9-SUBSTITUTED GUANINE DERIVATIVES AND INTERMEDIATES FOR USE IN THE PROCESS
  申请人：A/S GEA FARMACEUTISK FABRIK

  公开号：WO1990011283A1

  公开（公告）日：1990-10-04

  (EN) A process for the preparation of 9-substituted guanine derivatives of general formula (I), in which R is C1-C4-alkyl optionally substituted with one or more hydroxy groups, or R is ($g(a)), benzyl, ribosyl, 2'-deoxyribosyl or (CH2)n-OR1 where n is 1 or 2, and R1 is CH2CH2OH or ($g(b)) or salts thereof, in which a 1-substituted 5-(thiocarbamoyl)amino-1H-imidazole-4-carboxamide of general formula (III), where R has the same meaning as in formula (I), is cyclized: a) by treatment with a heavy metal salt of the group of Cu-, Ag-, Pb- and Hg-salts in an aqueous alkaline medium containing at least four equivalents of OH-ions at a temperature from about 0°C to the reflux temperature, or b) by treatment with a peroxy compound in an aqueous alkaline medium at a temperature of about 0-30°C, whereafter (I) is isolated by treatment with acid and, if desired, is converted into a salt. The invention further comprises intermediates for use in the preparation of the above-mentioned compounds.(FR) L'invention concerne un procédé de préparation de dérivés de guanine substitués en position 9, selon la formule générale (I), dans laquelle R représente alcoyle C1-C4 facultativement remplacé par un ou plusieurs groupes hydroxy, où R représente ($g(a)), benzyle, ribosyle, 2'-désoxyribosyle ou (CH2)n-OR1 où n représente 1 ou 2, et R1 représente CH2CH2OH ou ($g(b)), ou leurs sels, dans lequel un 5-(thiocarbamoyle) amino-1H-imidazole-4-carboxamide substitué en position 1, de la formule générale (III), dans laquelle R est défini comme dans la formule (I), est cyclisé: a) par traitement à l'aide d'un sel de métal lourd du groupe composé de sels de Cu, Ag, Pb et Hg dans un milieu alcalin aqueux contenant au moins quatre équivalents d'ions OH-, à température comprise entre environ 0°C et la température de reflux ou b) par traitement à l'aide d'un composé peroxy dans un milieu alcalin aqueux à une température comprise entre environ 0 et 30°C, après quoi (I) est isolé par traitement à l'acide, et si désiré, est transformé en un sel. L'invention comprend en outre des intermédiaires utilisés dans la préparation des composés précités.

  一种制备9-取代鸟嘌呤衍生物的方法，其一般式为（I），其中R是C1-C4烷基，可选择地取代一个或多个羟基，或者R是（$g(a)），苄基，核糖基，2'-去氧核糖基或（CH2）n-OR1，其中n为1或2，R1为CH2CH2OH或（$g(b)）或其盐，其中通过将一种一般式（III）的1-取代5-（硫氨酰）氨基-1H-咪唑-4-羧酰胺，其中R与公式（I）中的含义相同，进行环化：a）通过在含有至少四当量OH-离子的水性碱性介质中，用Cu-、Ag-、Pb-和Hg-盐中的重金属盐处理，在0°C至沸点温度范围内进行，或b）通过在水性碱性介质中使用过氧化物化合物，在约0-30°C的温度下进行处理，然后通过酸处理分离出（I），如有需要，转化为盐。该发明还包括用于制备上述化合物的中间体。
• Studies on the π–π stacking features of imidazole units present in a series of 5-amino-1-alkylimidazole-4-carboxamides
  作者：Sibdas Ray、Aniruddha Das

  DOI：10.1016/j.molstruc.2015.02.032

  日期：2015.6

  Reaction of 2-ethoxymethyleneamino-2-cyanoacetamide with primary alkyl amines in acetonitrile solvent affords 1-substituted-5-aminoimidazole-4-carboxamides. Single crystal X-ray diffraction studies of these imidazole compounds show that there are both anti-parallel and syn-parallel pi-pi stackings between two imidazole units in parallel-displaced (PD) conformations and the distance between two pi-pi stacked imidazole units depends mainly on the anti/ syn-parallel nature and to some extent on the alkyl group attached to N-1 of imidazole; molecules with anti-parallel PD-stacking arrangements of the imidazole units have got vertical pi-pi stacking distance short enough to impart stabilization whereas the imidazole unit having syn-parallel stacking arrangement have got much larger pi-pi stacking distances. DFT studies on a pair of anti-parallel imidazole units of such an AICA lead to curves for 'pi-pi stacking stabilization energy vs. pi-pi stacking distance' which have got similarity with the 'Morse potential energy diagram for a diatomic molecule' and this affords to find out a minimum pi-pi stacking distance corresponding to the maximum stacking stabilization energy between the pair of imidazole units. On the other hand, a DFT calculation based curve for 'pi-pi stacking stabilization energy vs. pi-pi stacking distance' of a pair of syn-parallel imidazole units is shown to have an exponential nature. (C) 2015 Elsevier B.V. All rights reserved.
• ALNEDE, VZHUSTORGE;SLAUSEN, FINN PRIESS;JUHL-CHRISTENSEN, JZHUSTORGEN;MSS+, J. ORG. CHEM., 56,(1991) N, C. 2139-2143
  作者：ALNEDE, VZHUSTORGE、SLAUSEN, FINN PRIESS、JUHL-CHRISTENSEN, JZHUSTORGEN、MSS+

  DOI：——

  日期：——