5-氨基咪唑-4-甲酰胺-1-β-D-呋喃核糖苷5-磷酸盐 | 3031-94-5

• 物质功能分类: 生物化工 - 核苷类药物 - 核苷中间体
• 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
• 中文名称: 5-氨基咪唑-4-甲酰胺-1-β-D-呋喃核糖苷5-磷酸盐
• 中文别名: 5-氨基咪唑-4-甲酰胺-1-Β-D-呋喃核糖苷5-一磷酸盐；5-氨基咪唑-4-甲酰胺-1-β-D-呋喃核糖苷5-一磷酸盐
• 英文名称: 5-aminoimidazole-4-carboxamide ribonucleotide
• 英文别名: aicar；5-aminoimidazole-4-carboxamine ribonucleotide；ZMP；5-aminoimidazole-4-carboxamide ribonucleoside；[(2R,3S,4R,5R)-5-(4-carbamoyl-5-aminoimidazol-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl dihydrogen phosphate；5-Amino-1-β-D-ribofuranosyl-imidazol-4-carbonsaeure-amid-5'-phosphat；5‐aminoimidazole‐4‐carboxamide ribonucleoside；5-aminoimidazole-4-carboxamide-1-β-riboside；AICA ribonucleotide；[(2R,3S,4R,5R)-5-(5-amino-4-carbamoylimidazol-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl dihydrogen phosphate
• CAS: 3031-94-5
• 化学式: C₉H₁₅N₄O₈P
• 分子量: 338.214
• InChiKey: NOTGFIUVDGNKRI-UUOKFMHZSA-N

物化性质

• 熔点：
  198-202°C dec.
• 沸点：
  845.3±75.0 °C(Predicted)
• 密度：
  2.30±0.1 g/cm3(Predicted)
• 溶解度：
  DMSO（微溶、加热、超声处理）、甲醇（微溶）、水（微溶）
• 物理描述：
  Solid
• 碰撞截面：
  171.6 Ų [M+H]+ [CCS Type: DT, Method: single field calibrated with Agilent tune mix (Agilent)]

计算性质

• 辛醇/水分配系数(LogP)：
  -3.8
• 重原子数：
  22
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  203
• 氢给体数：
  6
• 氢受体数：
  10

安全信息

• 安全说明：
  S24/25
• WGK Germany：
  3
• 海关编码：
  29349990

反应信息

• 作为反应物：
  描述：

  5-氨基咪唑-4-甲酰胺-1-β-D-呋喃核糖苷5-磷酸盐 在 三正丁胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 51.0h， 生成 diphosphoric acid-1-adenosin-5'-yl ester-2-[(1R)-1-(5-amino-4-carbamoyl-imidazol-1-yl)-D-1,4-anhydro-ribitol-5-yl ester]
  参考文献：
  名称：

  Ribavirin, tiazofurin, and selenazofurin: mononucleotides and nicotinamide adenine dinucleotide analogs. Synthesis, structure, and interactions with IMP dehydrogenase

  摘要：

  A series of dinucleotides, analogous to nicotinamide adenine dinucleotide but containing the five-membered base nucleosides tiazofurin (1a), selenazofurin (1b), ribavirin (2), and AICAR (3) in place of nicotinamide ribonucleoside, were prepared in greater than 50% yield by reacting the corresponding nucleotide imidazolidates (6a-d) with adenosine 5'-monophosphate (AMP). The symmetric dinucleotides of tiazofurin (TTD, 8e) and selenazofurin (SSD, 8f) were also prepared by a similar methodology. These dinucleotides were characterized by 1H NMR and fast atom bombardment MS and were evaluated for their inhibitory potency against a partially purified preparation of tumoral inosine monophosphate dehydrogenase (IMPD) from P388 cells. The order of potency found was SAD (8b) greater than TAD (8a) much greater than SSD (8f) congruent to TTD (8e) congruent to RAD (8c) much much greater than ZAD (8d). On kinetic analysis none of the dinucleotides produced competitive inhibition of IMPD with NAD as a variable substrate. In addition to their superior IMPD inhibitory activity, SAD and TAD appear to be the only dinucleotides, besides NAD, that are formed naturally by the NAD pyrophosphorylase from P388 lymphoblasts.

  DOI：

  10.1021/jm00379a018
• 作为产物：
  描述：

  阿卡地新 在 enzyme-extracts from pigeon's liver 、 5’-三磷酸腺苷 作用下， 生成 5-氨基咪唑-4-甲酰胺-1-β-D-呋喃核糖苷5-磷酸盐
  参考文献：
  名称：

  Greenberg, 1953, vol. 12, p. 211

  摘要：

  DOI：

文献信息

• [EN] 1 -OXO-1,2-DIHYDROISOQUINOLIN-7-YL-(5-SUBSTITUTED-THIOPHEN-2-YL)-SULFONAMIDE COMPOUNDS, FORMULATIONS CONTAINING THOSE COMPOUNDS, AND THEIR USE AS AICARFT INHIBITORS IN THE TREATMENT OF CANCERS<br/>[FR] COMPOSÉS 1-OXO-1,2-DIHYDROISOQUINOLÉINE-7-YL-(5-SUBSTITUÉ-THIOPHÉN-2-YL)-SULFONAMIDE, FORMULATIONS CONTENANT CES COMPOSÉS ET LEUR UTILISATION COMME INHIBITEURS D'AICARFT DANS LE TRAITEMENT DE CANCERS
  申请人：LILLY CO ELI

  公开号：WO2016089670A1

  公开（公告）日：2016-06-09

  1-Oxo-1,2-dihydroisoquinolin-7-yl-(5-substituted-thiophen-2-yl)-sulfonamide compounds, formulations containing those compounds, and their use as AICARFT inhibitors.

  1-Oxo-1,2-二氢异喹啉-7-基-(5-取代噻吩-2-基)-磺酰胺化合物，含有这些化合物的配方，以及它们作为AICARFT抑制剂的用途。
• Facile Solid-Phase Synthesis of AICAR 5′-Monophosphate (ZMP) and Its 4-<i>N</i>-Alkyl Derivatives
  作者：Giorgia Oliviero、Stefano D'Errico、Nicola Borbone、Jussara Amato、Vincenzo Piccialli、Gennaro Piccialli、Luciano Mayol

  DOI：10.1002/ejoc.200901271

  日期：2010.3

  solid-phase synthesis of 5-amino-1-β-D-ribofuranosylimidazole-4-carboxamide-5'-monophosphate (ZMP), a biosynthetic precursor of purine nucleotides, as well as a small collection of its 4-N-alkyl derivatives. The very difficult, direct, chemical phosphorylation of 5-amino-1-β-D-ribofuranosylimidazole-4-carboxamide (AICAR) was circumvented by installing a suitable, fully protected, phosphate group on the

  我们在此报告了一种简便的固相合成 5-amino-1-β-D-ribofuranosylimidazole-4-carboxamide-5'-monophosphate (ZMP)，一种嘌呤核苷酸的生物合成前体，以及它的一小部分4-N-烷基衍生物。5-amino-1-β-D-ribofuranosylimidazole-4-carboxamide (AICAR) 非常困难、直接的化学磷酸化通过在 N-1-的 5'-位安装一个合适的、完全保护的磷酸基团来规避(2,4-二硝基苯基)-肌苷，在嘌呤降解之前通过 2',3'-位连接到固体支持物，导致 5-氨基-咪唑-4-甲酰胺部分。还报道了形成 ZMP 咪唑的合理反应机制。
• AMP-ACTIVATED PROTEIN KINASE ACTIVATING COMPOUNDS AND USES THEREOF
  申请人：Skylark Bioscience LLC

  公开号：US20210230209A1

  公开（公告）日：2021-07-29

  The present invention relates to pharmaceutical compounds, compositions and methods, especially as they relate to the treatment and/or prevention of conditions associated with activation of AMP-activated protein kinase, wherein the compound is of Formula (I): as described herein, including pharmaceutically acceptable salts thereof and pharmaceutical compositions comprising such compounds, as well as methods to use these positions for treating indications including cancer, diabetes, ischemic injury, obesity, hyperlipidemia, and cardiac conditions.

  本发明涉及制药化合物、组合物和方法，特别是涉及与AMP激活蛋白激酶活化相关的疾病的治疗和/或预防，其中该化合物为式（I）所述，包括其药学上可接受的盐和包含这些化合物的制药组合物，以及使用这些位置治疗包括癌症、糖尿病、缺血性损伤、肥胖症、高脂血症和心脏疾病等症状的方法。
• Mass spectrometric analysis of purine de novo biosynthesis intermediates
  作者：Lucie Mádrová、Matyáš Krijt、Veronika Barešová、Jan Václavík、David Friedecký、Dana Dobešová、Olga Součková、Václava Škopová、Tomáš Adam、Marie Zikánová

  DOI：10.1371/journal.pone.0208947

  日期：——

  studied cleaved the glycosidic bond in the first fragmentation stage. Fragmentation was possible in the third to sixth stages. A liquid chromatography-high-resolution mass spectrometric method was developed and applied in the analysis of CRISPR-Cas9 genome-edited HeLa cells deficient in the individual enzymatic steps of PDNS and the salvage pathway. The identities of the newly synthesized intermediates

  嘌呤是所有形式生命中必不可少的分子。嘌呤除了构成DNA和RNA的骨架外，还在许多代谢途径中发挥作用，例如能量利用，酶活性调节和细胞信号传导。嘌呤的供应通过两种途径提供：挽救途径和从头合成。虽然嘌呤从头合成（PDNS）活性在细胞周期中会发生变化，该途径代表了嘌呤的重要来源，特别是对于快速分裂的细胞。由于分析原因（敏感性）以及由于该化合物在商业上的不实用性，缺乏用于PDNS的详细研究的方法。目的是全面描述新合成的与PDNS相关的代谢物的质谱碎片化行为，并开发一种分析方法。除了四个优先的核糖体PDNS中间体优先失去水或磷酸盐或裂解嘌呤环的形成碱基外，所有其他研究的代谢物均在第一个裂解阶段裂解了糖苷键。在第三到第六阶段可能会出现碎片。开发了一种液相色谱-高分辨率质谱法，并将其用于CRISPR-Cas9基因组编辑的HeLa细胞的分析，这些细胞在PDNS的各个酶促步骤和挽救途径中均存在缺陷。通过比较合
• Identification of the Formycin A Biosynthetic Gene Cluster from <i>Streptomyces kaniharaensis</i> Illustrates the Interplay between Biological Pyrazolopyrimidine Formation and <i>de Novo</i> Purine Biosynthesis
  作者：Shao-An Wang、Yeonjin Ko、Jia Zeng、Yujie Geng、Daan Ren、Yasushi Ogasawara、Seema Irani、Yan Zhang、Hung-wen Liu

  DOI：10.1021/jacs.9b00241

  日期：2019.4.17

  cosmid is identified from the Streptomyces kaniharaensis genome library that contains the for gene cluster responsible for the biosynthesis of formycin. Subsequent gene deletion experiments and in vitro characterization of the forBCH gene products established their catalytic functions in formycin biosynthesis. Results also demonstrated that PurH from de novo purine biosynthesis plays a key role in pyrazolopyrimidine

  Formycin A 是一种有效的嘌呤核苷抗生素，在核糖基部分和吡唑并嘧啶碱基之间具有 C-糖苷键。在此，从卡尼哈拉链霉菌基因组文库中鉴定出粘粒，其含有负责福霉素生物合成的基因簇。随后的基因缺失实验和 forBCH 基因产物的体外表征确定了它们在福霉素生物合成中的催化功能。结果还表明，来自嘌呤从头生物合成的 PurH 在福霉素 A 生物合成过程中吡唑并嘧啶的形成中起着关键作用。PurH 在这两种途径中的参与代表了初级和次级代谢如何相互关联的一个很好的例子。