(1R,2S,3R,4R)-2-Amino-9-(2,3-dihydroxy-4-hydroxymethylcyclopentyl)-1,9-dihydropurin-6-one | 111687-37-7

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 核苷和核苷酸类似物
• 英文名称: (1R,2S,3R,4R)-2-Amino-9-(2,3-dihydroxy-4-hydroxymethylcyclopentyl)-1,9-dihydropurin-6-one
• 英文别名: 2-amino-9-((1R,2S,3R,4R)-2,3-dihydroxy-4-(hydroxymethyl)cyclopentyl)-1H-purin-6(9H)-one；guanosine；2-amino-9-(2,3-dihydroxy-4-hydroxymethyl-cyclopentyl)-1,9-dihydro-purin-6-one；HSV-TK substrate；2-amino-9-[(1R,2S,3R,4R)-2,3-dihydroxy-4-(hydroxymethyl)cyclopentyl]-1H-purin-6-one
• CAS: 111687-37-7
• 化学式: C₁₁H₁₅N₅O₄
• 分子量: 281.271
• InChiKey: KIDOTSCXAILVGR-APOSLCTFSA-N

物化性质

• 溶解度：
  溶于二甲基亚砜

计算性质

• 辛醇/水分配系数(LogP)：
  -1.3
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  146
• 氢给体数：
  5
• 氢受体数：
  6

制备方法与用途

生物活性

HSV-TK substrate 是 HSV-TK 的底物，并在表达 HSV-T K 和 bystander 细胞中诱导 multi-log 细胞毒性，具有抗肿瘤活性。

反应信息

• 作为反应物：
  描述：

  (1R,2S,3R,4R)-2-Amino-9-(2,3-dihydroxy-4-hydroxymethylcyclopentyl)-1,9-dihydropurin-6-one 在 吡啶 、 咪唑 、 三甲基氯硅烷 作用下， 以 吡啶 为溶剂， 反应 13.05h， 生成 N-(9-((1R,2S,3R,4R)-4-((bis(4-methoxyphenyl)(phenyl)methoxy)methyl)-2-((tert-butyldimethylsilyl)oxy)-3-hydroxycyclopentyl)-6-oxo-6,9-dihydro-1H-purin-2-yl)isobutyramide
  参考文献：
  名称：

  [EN] CYCLIC DI-NUCLEOTIDES AS MODULATORS OF STING
  [FR] DI-NUCLÉOTIDES CYCLIQUES UTILISÉS COMME MODULATEURS DE STING

  摘要：

  一种化合物的公式(I)或其药学上可接受的盐和互变异构体，包括含有该化合物的组合物、混合物和药物，以及它们的制备方法。本发明还涉及使用该化合物、组合物、混合物和药物在治疗调节STING（干扰素基因刺激剂）有益的疾病和状况方面的用途，例如炎症、过敏和自身免疫性疾病、传染病、癌症和作为疫苗佐剂。

  公开号：

  WO2015185565A1
• 作为产物：
  描述：

  在 盐酸 作用下， 以 水 为溶剂， 生成 (1R,2S,3R,4R)-2-Amino-9-(2,3-dihydroxy-4-hydroxymethylcyclopentyl)-1,9-dihydropurin-6-one
  参考文献：
  名称：

  Synthesis from (–)-aristeromycin and X-ray structure of (–)-carbovir

  摘要：

  Efficient processes are described for the synthesis of (-)-carbovir 3 and its triphosphate derivative 28 from (-)-aristeromycin 4. The X-ray structure of (-)-carbovir has been determined.

  DOI：

  10.1039/p19910002467

文献信息

• Base-Functionalized Carbocyclic Nucleosides: Design, Synthesis, and Mechanism of Antiviral Activity
  作者：Vasu Nair、Fan Zhang、Xiaohui Ma、Eric Bonsu

  DOI：10.1080/15257770903044465

  日期：2009.8.11

  nucleobase were designed as potential RNA antiviral compounds. The design was based on the expectation that the monophosphates of these compounds would be inhibitors of the enzyme, IMPDH. Appropriate methodologies were developed to achieve the target molecules. Results from the initial in vitro antiviral studies are mentioned. The IMPDH-associated mechanism of the antiviral activity of the most active

  在核碱基的 C-2 位置具有不饱和基团的新碳环核糖核苷被设计为潜在的 RNA 抗病毒化合物。该设计基于预期这些化合物的单磷酸盐将成为酶 IMPDH 的抑制剂。开发了适当的方法来实现目标分子。提到了最初的体外抗病毒研究的结果。酶抑制研究支持了最活跃化合物抗病毒活性的 IMPDH 相关机制。
• Nucleotide analogs, their production and use
  申请人：Takeda Chemical Industries, Ltd.

  公开号：EP0278501A2

  公开（公告）日：1988-08-17

  The carbocyclic nuucleotides represented by the formula wherein Y stands for a purine base residue or 5-amino-4-carbamoyl-imidazol-1-yl; X stands for hydrogen or an optionally protected hydroxyl group provided that, when Y is adenin-9-yl; X is hydrogen; R, and R2 independently or combinedly represent phosphoryl group; which shows antiviral action.

  式中 Y 代表嘌呤碱残基或 5-氨基-4-氨基甲酰基咪唑-1-基；X 代表氢或任选受保护的羟基。 其中 Y 代表嘌呤碱残基或 5-氨基-4-氨基甲酰基-咪唑-1-基；X 代表氢或任选保护的羟基，条件是当 Y 为腺嘌呤-9-基时；X 为氢；R 和 R2 独立或合并代表磷酸基；这些核苷酸具有抗病毒作用。
• Cyclic di-nucleotides as modulators of STING
  申请人：GlaxoSmithKline Intellectual Property Development Limited

  公开号：US10450341B2

  公开（公告）日：2019-10-22

  A compound of formula (1) Or a pharmaceutically acceptable salt and tautomers thereof, compositions, combinations and medicaments containing said compounds and processes for their preparation. The invention also relates to the use of said compounds, combinations, compositions and medicaments, in the treatment of diseases and conditions in which modulation of STING (Stimulator of Interferon Genes) is beneficial, for example inflammation, allergic and autoimmune diseases, infectious diseases, cancer and as vaccine adjuvants.

  式(1)化合物 或其药学上可接受的盐和同系物，含有上述化合物的组合物、复合制剂和药物，以及其制备工艺。本发明还涉及上述化合物、组合物、组合物和药物在治疗调节 STING（干扰素基因刺激因子）有益的疾病和病症中的用途，例如炎症、过敏性和自身免疫性疾病、传染性疾病、癌症以及作为疫苗佐剂。
• Impdh As A Biological Probe For Rna Antiviral Drug Discovery: Synthesis, Enzymology, Molecular Docking, And Antiviral Activity Of New Ribonucleosides With Surrogate Bases
  作者：Vasu Nair、Xiaohui Ma、Qingning Shu、Fan Zhang、Vinod Uchil、Govardhan R. Cherukupalli

  DOI：10.1080/15257770701490506

  日期：2007.11.26

  Our interest in the discovery of molecules with antiviral activity against RNA viruses led us to the design of ribonucleosides with surrogate bases with the intent Of using inhibition of inosine monophosphate dehydrogenase (IMPDH) as a probe for antiviral drug discovery. A general methodology for the preparation of these compounds is discussed. Kinetic parameters of the inhibition studies with IMPDH, which were carried out spectrophotometrically by monitoring the formation of NADH, are given. Antiviral information and correlation of activity with IMPDH inhibition are discussed.
• CYCLIC DI-NUCLEOTIDES AS MODULATORS OF STING
  申请人：GlaxoSmithKline Intellectual Property Development Limited

  公开号：EP3152217B1

  公开（公告）日：2018-08-01