5-amino-1-(β-D-ribofuranosyl)imidazole-4-carboxamidoxime | 57004-06-5

• 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: 5-amino-1-(β-D-ribofuranosyl)imidazole-4-carboxamidoxime
• 英文别名: 5-amino-N-hydroxy-1-β-D-ribofuranosyl-1H-imidazole-4-carboximidic acid amide；5-amino-1β-D-ribofuranosyl-1H-imidazole-4-carboxamide oxime；5-Amino-1β-D-ribofuranosyl-1H-imidazol-4-carbamidoxim；5-amino-1-β-D-ribofuranosylimidazole-4-carboxamide oxime；5-amino-1-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-N'-hydroxyimidazole-4-carboximidamide
• CAS: 57004-06-5
• 化学式: C₉H₁₅N₅O₅
• 分子量: 273.249
• InChiKey: DWVZGPBTFUTAAC-UUOKFMHZSA-N

物化性质

• 沸点：
  725.7±70.0 °C(Predicted)
• 密度：
  2.10±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -1.9
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  172
• 氢给体数：
  6
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  5-amino-1-(β-D-ribofuranosyl)imidazole-4-carboxamidoxime 在 ammonium sulfide 、 sodium dithionite 作用下， 以 甲醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 5.67h， 生成 2-(丙硫基)腺苷
  参考文献：
  名称：

  New highly active antiplatelet agents with dual specificity for platelet P2Y1 and P2Y12 adenosine diphosphate receptors

  摘要：

  Currently approved platelet adenosine diphosphate (ADP) receptor antagonists target only the platelet P2Y(12) receptor. Moreover, especially in patients with acute coronary syndromes, there is a strong need for rapidly acting and reversible antiplatelet agents in order to minimize the risk of thrombotic events and bleeding complications. In this study, a series of new P-1,P-4-di(adenosine-5') tetraphosphate (Ap(4)A) derivatives with modifications in the base and in the tetraphosphate chain were synthesized and evaluated with respect to their effects on platelet aggregation and function of the platelet P2Y(1), P2Y(12), and P2X1 receptors. The resulting structure activity relationships were used to design Ap(4)A analogs which inhibit human platelet aggregation by simultaneously antagonizing both P2Y(1) and P2Y(12) platelet receptors. Unlike Ap(4)A, the analogs do not activate platelet P2X1 receptors. Furthermore, the new compounds exhibit fast onset and offset of action and are significantly more stable than Ap(4)A to degradation in plasma, thus presenting a new promising class of antiplatelet agents. (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.10.055
• 作为产物：
  描述：

  5-amino-1-β-D-ribofuranosylimidazole-4-carbonitrile 在 羟胺 作用下， 以 乙醇 为溶剂， 以98.8%的产率得到5-amino-1-(β-D-ribofuranosyl)imidazole-4-carboxamidoxime
  参考文献：
  名称：

  Analogs of AICA- and IsoAICA Ribosides and Their Methylated Base Counterparts

  摘要：

  A mild, convenient and efficient synthesis has been developed for imidazole-4-thiocarboxamide and imidazole-5-thiocarboxamide ribosides and the analogous selenocarboxamides. This methodology, i.e., DMF saturated with H2S or H2Se, also converts the corresponding N-methylated bases to the corresponding amides. The imidazole-4(5)-selenocarboxamides were shown to be sensitive to base (pH 11) and were easily converted back to their cyano precursors. The kinetics of these reactions were determined and they indicate that the C5 amides were more reactive than their C4 analogs.

  DOI：

  10.1080/07328319908044611
• 作为试剂：
  描述：

  adenosine 1-oxide monohydrate 、 sodium hydroxide 、 、 甲醇 、 二硫化碳 在 5-amino-1-(β-D-ribofuranosyl)imidazole-4-carboxamidoxime 、 氨 、 正丁醇 、 溶剂黄146 作用下， 反应 5.25h， 以to obtain 8.20 g of 2-thioadenosine having a melting point of 199° C (with decomposition) in a 97% yield的产率得到2-硫代腺苷酸
  参考文献：
  名称：

  Process for preparing 2-thioadenosine

  摘要：

  一种制备2-硫基腺苷的方法，用作制备具有血小板聚集抑制活性和冠状动脉扩张活性的S-取代-2-硫基腺苷的中间体，包括在溶剂中的封闭反应区内，将5-氨基-1-β-D-核糖呋喃基咪唑-4-甲酰胺肟或其O-取代肟与二硫化碳反应，在温度约50℃至约200℃之间进行反应。

  公开号：

  US03989682A1

文献信息

• Nucleoside-5′-monophosphates as Prodrugs of Adenosine A_2A Receptor Agonists Activated by ecto-5′-Nucleotidase†Contribution to celebrate the 100th anniversary of the Division of Medicinal Chemistry of the American Chemical Society.
  作者：Ali El-Tayeb、Jamshed Iqbal、Andrea Behrenswerth、Michael Romio、Marion Schneider、Herbert Zimmermann、Jürgen Schrader、Christa E. Müller

  DOI：10.1021/jm900538v

  日期：2009.12.10

  Prodrugs of adenosine A2A receptor agonists were developed that are activated by ecto-5′-nucleotidase (ecto-5′-NT, CD73). Because ecto-5′-NT is upregulated in inflamed tissue, the A2A agonists are expected to be released from their prodrug form at the sites of inflammation. 2-(Ar)alkyl-substituted AMP derivatives were synthesized and investigated. Certain 2-substituted AMP derivatives, including 2-hexylthio-AMP

  开发了腺苷A 2A受体激动剂的前药，它们被ecto-5'-核苷酸酶（ecto-5'-NT，CD73）激活。由于ecto-5'-NT在发炎的组织中上调，因此A 2A激动剂有望在炎症部位从其前药形式释放出来。合成并研究了2-（Ar）烷基取代的AMP衍生物。某些2-取代的AMP衍生物，包括2-己基硫基-AMP，2-环戊基硫基-AMP，2-环己基甲硫基-AMP和2-环己基乙硫基-AMP被ecto-5'-NT接受为底物，并易于转化为相应的2取代的腺苷衍生物。2-环己基乙硫基取代是ecto-5'-NT和腺苷A 2A的良好折衷方案受体。相应的AMP衍生物（12g）是与AMP本身相似的良好底物，而所得的腺苷衍生物（11g）是相对有效的A 2A激动剂（放射配体与大鼠脑纹状体膜的结合力：K i = 372 nM；抑制抗-在小鼠CD4 +细胞中CD3 /抗CD28诱导的IFN-γ释放：EC 50 = 50 nM
• 2-Substituted α,β-Methylene-ADP Derivatives: Potent Competitive Ecto-5′-nucleotidase (CD73) Inhibitors with Variable Binding Modes
  作者：Sanjay Bhattarai、Jan Pippel、Emma Scaletti、Riham Idris、Marianne Freundlieb、Georg Rolshoven、Christian Renn、Sang-Yong Lee、Aliaa Abdelrahman、Herbert Zimmermann、Ali El-Tayeb、Christa E. Müller、Norbert Sträter

  DOI：10.1021/acs.jmedchem.9b01611

  日期：2020.3.26

  CD73 inhibitors are promising drugs for the (immuno)therapy of cancer. Here, we present the synthesis, structure-activity relationships, and cocrystal structures of novel derivatives of the competitive CD73 inhibitor α,β-methylene-ADP (AOPCP) substituted in the 2-position. Small polar or lipophilic residues increased potency, 2-iodo- and 2-chloro-adenosine-5'-O-[(phosphonomethyl)phosphonic acid] (15

  CD73抑制剂是用于癌症（免疫）治疗的有前途的药物。在这里，我们介绍了合成，结构-活性关系，和竞争性CD73抑制剂α，β-亚甲基-ADP（AOPCP）取代2位的新型衍生物的共晶体结构。小极性或亲脂性残基增加了效力，2-碘-和2-氯腺苷-5'-O-[（膦酰基甲基）膦酸]（15、16）是对人CD73的Ki值为3-的最有效抑制剂6 nM。取决于2-取代基的大小和性质，通过X射线晶体学观察到可变的结合模式。取决于结合模式，发现了较大的物种差异，例如，2-哌嗪基-AOPCP（21）与人CD73相比，对大鼠CD73的效力低> 12倍。这项研究表明，只需将一个小的取代基引入AOPCP的2位即可实现高CD73抑制力，而无需额外的大体积N6-取代基。此外，它为竞争性CD73抑制剂的结合模式提供了宝贵的见解，为药物开发提供了极好的基础。
• Synthesis of 3-Aminoimidazo[4,5-<i>c</i>]pyrazole Nucleoside via the N-N Bond Formation Strategy as a [5:5] Fused Analog of Adenosine
  作者：Tun-Cheng Chien、David A. Berry、John C. Drach、Leroy B. Townsend

  DOI：10.1080/15257770500269531

  日期：2005.9.1

  3-Amino-6-(β-D-ribofuranosyl)imidazo[4,5-c]pyrazole (2) was synthesized via an N-N bond formation strategy by a mononuclear heterocyclic rearrangement (MHR). A series of 5-amino-1-(5-O-tert-butyldimethylsilyl-2,3-O-isopropylidene-β-D-ribofuranosyl-4-(1,2,4-oxadiazol-3-yl)imidaz-oles (6a-d), with different substituents at the 5-position of the 1,2,4-oxadiazole, were synthesized from 5-amino-1-(β-D-

  3-氨基-6-(β-D-呋喃核糖基)咪唑并[4,5-c]吡唑(2)是通过单核杂环重排(MHR)的NN键形成策略合成的。一系列 5-amino-1-(5-O-tert-butyldimethylsilyl-2,3-O-isopropylidene-β-D-ribofuranosyl-4-(1,2,4-oxadiazol-3-yl)imidaz-oles (6a-d)，在 1,2,4-恶二唑的 5-位具有不同的取代基，由 5-氨基-1-(β-D-呋喃核糖基)咪唑-4-甲酰胺 (AICA Ribose, 3 ). 发现5-氨基-1-(5-O-叔丁基二甲基甲硅烷基-2,3-O-异亚丙基-β-D-呋喃核糖基)-4-(5-甲基-1,2,4-恶二唑-3-基）咪唑（6a）与氢化钠在 DMF 或 DMSO 中进行 MHR，以良好的产率得到相应的 3-乙酰氨基咪唑并[4,5-c]吡唑核苷（7b 和/或 7a）。从
• 一种坎格雷洛中间体的制备方法
  申请人：南通宏慈药业有限公司

  公开号：CN105693800A

  公开（公告）日：2016-06-22

  本发明涉及一种如式（I）：所示的坎格雷洛中间体的制备方法，所述制备方法以式（II）所示的结构化合物为原料，在溶剂和反应试剂下，经特定反应，反应后的产物再经纯化得到式（I）所示的坎格雷洛中间体；其中，式（II）的具体结构为： 本发明的优点在于：本发明的制备方法，操作简便、产物纯度较高，反应过程安全性高，适合工业化生产，且成本低廉。
• Purine N-Oxides. V. Oxides of Adenine Nucleotides¹
  作者：Marcus A. Stevens、Herman W. Smith、George Bosworth Brown

  DOI：10.1021/ja01516a053

  日期：1959.4