(1R)-1-(4-aminofuro[3,2-d]pyrimidin-7-yl)-1,4-anhydro-2-C-methyl-2,3-O-(1-methylethylidene)-5-O-trityl-D-ribitol

• 分子结构分类: 有机化合物 - 苯类化合物 - 三苯基化合物
• 英文名称: (1R)-1-(4-aminofuro[3,2-d]pyrimidin-7-yl)-1,4-anhydro-2-C-methyl-2,3-O-(1-methylethylidene)-5-O-trityl-D-ribitol
• 英文别名: 7-((3aS,4S,6R,6aR)-2,2,3a-trimethyl-6-(trityloxymethyl)tetrahydrofuro[3,4-d][1,3]dioxol-4-yl)furo[3,2-d]pyrimidin-4-amine；7-[(3aS,4S,6R,6aR)-2,2,3a-trimethyl-6-(trityloxymethyl)-6,6a-dihydro-4H-furo[3,4-d][1,3]dioxol-4-yl]furo[3,2-d]pyrimidin-4-amine
• 化学式: C₃₄H₃₃N₃O₅
• 分子量: 563.653
• InChiKey: RJDPTMLXHZFTDD-GJBCBESVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  42
• 可旋转键数：
  7
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  102
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  (1R)-1-(4-aminofuro[3,2-d]pyrimidin-7-yl)-1,4-anhydro-2-C-methyl-2,3-O-(1-methylethylidene)-5-O-trityl-D-ribitol 在 盐酸 作用下， 以 1,4-二氧六环 、 甲醇 为溶剂， 反应 2.0h， 生成 (2S,3R,4R,5R)-2-(4-aminofuro[3,2-d]pyrimidin-7-yl)-5-(hydroxymethyl)-3-methyl-tetrahydrofuran-3,4-diol
  参考文献：
  名称：

  [EN] C-PURINE NUCLEOSIDE ANALOGS AS INHIBITORS OF RNA-DEPENDENT RNA VIRAL POLYMERASE
  [FR] ANALOGUES NUCLEOSIDIQUES DE C-PURINE, SERVANT D'INHIBITEURS D'ARN-POLYMERASE VIRALE ARN-DEPENDANTE

  摘要：

  公开号：

  WO2005123087A3
• 作为产物：
  描述：

  (1R)-1-(4-amino-5-cyano-3-furyl)-1,4-anhydro-2-C-methyl-2,3-O-(1-methylethylidene)-5-O-trityl-D-ribitol 、 醋酸甲脒 以 乙醇 为溶剂， 以58%的产率得到(1R)-1-(4-aminofuro[3,2-d]pyrimidin-7-yl)-1,4-anhydro-2-C-methyl-2,3-O-(1-methylethylidene)-5-O-trityl-D-ribitol
  参考文献：
  名称：

  Ribo 7-N/O/S 嘧啶 9-脱氮 C-核苷类似物作为抑制 HCV RNA 依赖性 RNA 聚合酶的新型抗病毒药物的合成和生物学评价

  摘要：

  丙型肝炎感染是由血源性病原体丙型肝炎病毒 (HCV) 引起的，如果治疗无效，可导致严重的肝脏疾病，并最终导致死亡。本工作报道了7种新型9-O/N/S嘧啶核苷的合成和临床前评价，其中包括化合物12 ，即已知化合物7b的三磷酸酯。核苷是腺苷和鸟苷的 9-脱氮修饰，核糖上带有 β-2'-C-甲基取代基。在该系列化合物中，腺苷的9-脱氮呋喃嘧啶类似物化合物7b在体外表现出高抗HCV活性，在低剂量给药时表现出良好的稳定性、低毒性和低遗传毒性，以及足够的药代动力学特征。与之前的研究相比，还报道了化合物7b的合成改进。合成化合物12作为对照以验证7b在体内发生的磷酸化。

  DOI：

  10.1016/j.ejmech.2023.115991

文献信息

• [EN] C-PURINE NUCLEOSIDE ANALOGS AS INHIBITORS OF RNA-DEPENDENT RNA VIRAL POLYMERASE<br/>[FR] ANALOGUES NUCLEOSIDIQUES DE C-PURINE, SERVANT D'INHIBITEURS D'ARN-POLYMERASE VIRALE ARN-DEPENDANTE
  申请人：MERCK & CO INC

  公开号：WO2005123087A3

  公开（公告）日：2006-07-13
• C-Purine Nucleoside Analogs As Inhibitors Of Rna-Dependent Rna Viral Polymerase
  申请人：Butora Gabor

  公开号：US20080021047A1

  公开（公告）日：2008-01-24

  The present invention provides C-purine nucleoside analogs and certain derivatives thereof which are inhibitors of RNA-dependent RNA viral polymerase. These compounds are inhibitors of RNA-dependent RNA viral replication and are useful for the treatment of RNA-dependent RNA viral infection. They are particularly useful as inhibitors of hepatitis C virus (HCV) NS5B polymerase, as inhibitors of HCV replication, and/or for the treatment of hepatitis C infection. The invention also describes pharmaceutical compositions containing such C-nucleoside compounds alone or in combination with other agents active against RNA-dependent RNA viral infection, in particular HCV infection. Also disclosed are methods of inhibiting RNA-dependent RNA polymerase, inhibiting RNA-dependent RNA viral replication, and/or treating RNA-dependent RNA viral infection with the C-nucleoside compounds of the present invention.
• US7534767B2
  申请人：——

  公开号：US7534767B2

  公开（公告）日：2009-05-19
• Synthesis and HCV inhibitory properties of 9-deaza- and 7,9-dideaza-7-oxa-2′-C-methyladenosine
  作者：Gabor Butora、David B. Olsen、Steven S. Carroll、Daniel R. McMasters、Christoph Schmitt、Joseph F. Leone、Mark Stahlhut、Christine Burlein、Malcolm MacCoss

  DOI：10.1016/j.bmc.2007.05.020

  日期：2007.8

  As a part of an ongoing medicinal chemistry effort to identify inhibitors of the Hepatitis C Virus RNA replication, we report here the synthesis and biological evaluation of 9-deaza- and 7,9-dideaza-7-oxa-2'-C-methyladenosine. The parent 2'-C-methyladenosine shows excellent intracellular inhibitory activity but poor pharmacokinetic profile. Replacement of the nucleoside-defining 9-N of 2'-C-methyladenosine with a carbon atom was designed to yield metabolically more stable C-nucleosides. Modifications at position 7 were designed to exploit the importance of the hydrogen bond accepting properties of this heteroatom in modulating the adenosine deaminase (ADA) mediated 6-N deamination. 7-Oxa-7,9-dideaza-2'-C-methyladenosine was found to be a moderately active inhibitor of intracellular HCV RNA replication, whereas 9-deaza- 2'-C-methyladenosine showed only weak activity despite excellent overlap of both of the synthesized target compounds with T-C-methyladenosine's three dimensional structure. Position 7 of the nucleobase proved to be an effective handle for modulating ADA-mediated degradation, with the rate of degradation correlating with the hydrogen-bonding properties at this position. (c) 2007 Elsevier Ltd. All rights reserved.
• Synthesis and biological evaluation of Ribo 7-N/O/S pyrimidine 9-deaza C-nucleoside analogs as new antiviral agents for inhibiting HCV RNA-dependent RNA polymerases
  作者：Minwan Wu、Satish Vadlakonda、Yahya El-Kattan、Ajit Ghosh、Tsu-Hsing Lin、Ramanda Chambers-Wilson、Xiaogang Cheng、Shanta Bantia、Debra Kellogg-Yelder、Pooran Chand、Y.S. Babu、Pravin L. Kotian

  DOI：10.1016/j.ejmech.2023.115991

  日期：2024.1

  ineffective. This work reports the synthesis and preclinical evaluation of 7 novel 9-O/N/S pyrimidine nucleosides, including compound 12, the triphosphate of compound of known compound 7b. The nucleosides are 9-deaza modifications of adenosine and guanosine with β-2′-C-methyl substituent on the ribose. Within this series of compounds, a 9-deaza furopyrimidine analog of adenosine, compound 7b, showed

  丙型肝炎感染是由血源性病原体丙型肝炎病毒 (HCV) 引起的，如果治疗无效，可导致严重的肝脏疾病，并最终导致死亡。本工作报道了7种新型9-O/N/S嘧啶核苷的合成和临床前评价，其中包括化合物12 ，即已知化合物7b的三磷酸酯。核苷是腺苷和鸟苷的 9-脱氮修饰，核糖上带有 β-2'-C-甲基取代基。在该系列化合物中，腺苷的9-脱氮呋喃嘧啶类似物化合物7b在体外表现出高抗HCV活性，在低剂量给药时表现出良好的稳定性、低毒性和低遗传毒性，以及足够的药代动力学特征。与之前的研究相比，还报道了化合物7b的合成改进。合成化合物12作为对照以验证7b在体内发生的磷酸化。