1-(β-D-ribofuranosyl)-5-(thiocarbamoyl)amino-1H-imidazole-4-carboxamide | 133068-54-9

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 咪唑核糖核苷和核糖核苷酸
• 英文名称: 1-(β-D-ribofuranosyl)-5-(thiocarbamoyl)amino-1H-imidazole-4-carboxamide
• 英文别名: 1-(beta-D-ribofuranosyl)-5-(thiocarbamoyl)amino-1H-imidazole-4-carboxamide；5-(carbamothioylamino)-1-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]imidazole-4-carboxamide
• CAS: 133068-54-9
• 化学式: C₁₀H₁₅N₅O₅S
• 分子量: 317.326
• InChiKey: DRPRDPXASLIYCT-UUOKFMHZSA-N

物化性质

• 沸点：
  768.8±70.0 °C(Predicted)
• 密度：
  2.05±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -2.3
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  201
• 氢给体数：
  6
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  1-(β-D-ribofuranosyl)-5-(thiocarbamoyl)amino-1H-imidazole-4-carboxamide 在 sodium hydroxide 、 copper diacetate 作用下， 反应 1.5h， 以53%的产率得到鸟苷
  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：

  阿卡地新 、 苯甲酰基异硫氰酸酯 在 potassium carbonate 作用下， 生成 1-(β-D-ribofuranosyl)-5-(thiocarbamoyl)amino-1H-imidazole-4-carboxamide
  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

• Process for the preparation of 9-substituted guanine derivatives
  申请人：A/S Gea Farmaceutisk Fabrik

  公开号：US05223619A1

  公开（公告）日：1993-06-29

  A process for the preparation of 9-substituted quanine derivatives of general formula (I), in which R is C.sub.1 -C.sub.4 -alkyl optionally substituted with one or more hydroxy groups, or R is (.alpha.), benzyl, ribosyl, 2'-deoxyribosyl or (CH.sub.2).sub.n -OR.sup.1 where n is 1 or 2, and R.sup.1 is CH.sub.2 CH.sub.2 OH or (.beta.) or salts thereof, in which a 1-substituted5-(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 for equivalents of OH-ions at a temperature form about 0.degree. C. to the reflux temperature, or b) by treatment with a peroxy compound in an aqueous alkaline medium at a temperature of about 0.degree.-30.degree. C., whereafter (I) is isolated by treatment with a acid and, if desired, is converted into a salt. The invention further comprises intermediates for use in the preparation of the above-mentioned compounds.

  一种制备一般式（I）中的9-取代喹啉衍生物的方法，其中R是C.sub.1-C.sub.4-烷基，可选择性地取代一个或多个羟基，或R是（α）、苄基、核糖基、2'-脱氧核糖基或（CH.sub.2）.sub.n-OR.sup.1，其中n为1或2，R.sup.1为CH.sub.2CH.sub.2OH或（β）或其盐，其中一种一般式（III）的1-取代5-(硫代氨基)-1H-咪唑-4-羧酰胺在具有与公式（I）中相同含义的R的情况下被环化：a）通过在含有至少四当量OH-离子的水性碱性介质中，以从大约0°C到沸点温度的温度进行处理，处理与Cu-、Ag-、Pb-和Hg-盐组的重金属盐，或b）通过在水性碱性介质中以约0°C至30°C的温度处理过氧化物化合物处理，之后通过与酸处理分离出（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。
• [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。
• 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：EP0464112B1

  公开（公告）日：1994-10-05
• US5223619A
  申请人：——

  公开号：US5223619A

  公开（公告）日：1993-06-29
• A simple and efficient synthesis of 9-substituted guanines. Cyclodesulfurization of 1-substituted 5-[(thiocarbamoyl)amino]imidazole-4-carboxamides under aqueous basic conditions
  作者：Boerge Alhede、Finn Priess Clausen、Joergen Juhl-Christensen、Klaus K. McCluskey、Herbert F. Preikschat

  DOI：10.1021/jo00006a033

  日期：1991.3

  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.