(2R,3S,4R,5R)-5-(2-amino-6-methoxy-9H-purin-9-yl)-4-azido-2-(hydroxymethyl)-4-methyltetrahydrofuran-3-ol | 1403249-88-6

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘌呤核苷
• 英文名称: (2R,3S,4R,5R)-5-(2-amino-6-methoxy-9H-purin-9-yl)-4-azido-2-(hydroxymethyl)-4-methyltetrahydrofuran-3-ol
• 英文别名: (2R,3S,4R,5R)-5-(2-amino-6-methoxypurin-9-yl)-4-azido-2-(hydroxymethyl)-4-methyloxolan-3-ol
• CAS: 1403249-88-6
• 化学式: C₁₂H₁₆N₈O₄
• 分子量: 336.31
• InChiKey: JARRBPDPRPOFEW-GSWPYSDESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.1
• 重原子数：
  24
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  143
• 氢给体数：
  3
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  (2R,3S,4R,5R)-5-(2-amino-6-methoxy-9H-purin-9-yl)-4-azido-2-(hydroxymethyl)-4-methyltetrahydrofuran-3-ol 在 吡啶 、 4,5-二氰基咪唑 、 碘 作用下， 以 四氢呋喃 、 水 、 乙腈 为溶剂， 反应 1.5h， 生成 9-[(4aR,6R,7R,7aS)-7-azido-7-methyl-2-oxo-2-propan-2-yloxy-4,4a,6,7a-tetrahydrofuro[3,2-d][1,3,2]dioxaphosphinin-6-yl]-6-methoxypurin-2-amine
  参考文献：
  名称：

  2'-AZIDO SUBSTITUTED NUCLEOSIDE DERIVATIVES AND METHODS OF USE THEREOF FOR THE TREATMENT OF VIRAL DISEASES

  摘要：

  本发明涉及式(I)的2'-叠氮基取代核苷衍生物及其药学上可接受的盐，其中B、X、R1、R2和R3如本文所定义。本发明还涉及包含至少一种2'-叠氮基取代核苷衍生物的组合物，以及使用这些2'-叠氮基取代核苷衍生物治疗或预防患者HCV感染的方法。

  公开号：

  US20140206640A1

文献信息

• [EN] 2'-SUBSTITUTED NUCLEOSIDE DERIVATIVES AND METHODS OF USE THEREOF FOR THE TREATMENT OF VIRAL DISEASES<br/>[FR] DÉRIVÉS DE NUCLÉOSIDE 2'-SUBSTITUÉS ET PROCÉDÉS D'UTILISATION DE CEUX-CI POUR LE TRAITEMENT DE MALADIES VIRALES
  申请人：MERCK SHARP & DOHME

  公开号：WO2012142085A1

  公开（公告）日：2012-10-18

  The present invention relates to 2'-Substituted Nucleoside Derivatives of Formula (I): and pharmaceutically acceptable salts thereof, wherein A, B, X, R1, R2 and R3 are as defined herein. The present invention also relates to compositions comprising at least one 2'-Substituted Nucleoside Derivative, and methods of using the 2'-Substituted Nucleoside Derivatives for treating or preventing HCV infection in a patient.

  本发明涉及式(I)的2'-取代核苷衍生物及其药学上可接受的盐，其中A、B、X、R1、R2和R3如本文所定义。本发明还涉及包含至少一种2'-取代核苷衍生物的组合物，以及使用这些2'-取代核苷衍生物治疗或预防患者HCV感染的方法。
• The protecting-group free selective 3′-functionalization of nucleosides
  作者：Jamie M. McCabe Dunn、Mikhail Reibarkh、Edward C. Sherer、Robert K. Orr、Rebecca T. Ruck、Bryon Simmons、Ana Bellomo

  DOI：10.1039/c6sc05081f

  日期：——

  The direct and chemoselective 3′-phosphoramidation, phosphorylation and acylation of nucleosides are described. Upon the discovery of a novel 3′-phosphorylamidation of therapeutic nucleoside analogues with DBU, we explored the mechanism of this rare selectivity through a combination of NMR spectroscopy and computational studies. The NMR and computational findings allowed us to develop a predictive

  描述了核苷的直接化学选择性 3'-氨基磷酸化、磷酸化和酰化。在发现 DBU 治疗性核苷类似物的新型 3'-磷酸酰胺化后，我们通过 NMR 光谱和计算研究的结合探索了这种罕见选择性的机制。NMR 和计算结果使我们能够开发出一种预测计算模型，该模型可以准确评估各种核苷和核苷模拟物的 3'-功能化潜力。该模型的合成实用性通过对广泛的核苷和亲电子试剂产生靶标的演示来举例说明，而这些靶标以前只能通过保护/去保护序列或酶促方法获得。
• Mechanism-Based Solution to the ProTide Synthesis Problem: Selective Access to Sofosbuvir, Acelarin, and INX-08189
  作者：Bryon Simmons、Zhuqing Liu、Artis Klapars、Ana Bellomo、Steven M. Silverman

  DOI：10.1021/acs.orglett.7b00469

  日期：2017.5.5

  A general and efficient method for the synthesis of pronucleotide (ProTide) 5'-phosphoramidate monoesters is :reported. This method consists of a highly stereoselective 5'-phosphorylation mediated by dimethylaluminum chloride to afford the desired target ProTides in excellent yields without employing, 3'-protection strategies. The application of this methodology to the synthesis of a number of pharmaceutically relevant compounds currently marketed or under investigation in clinical research is demonstrated.
• 2'-SUBSTITUTED NUCLEOSIDE DERIVATIVES AND METHODS OF USE THEREOF FOR THE TREATMENT OF VIRAL DISEASES
  申请人：Girijavallabhan Vinay

  公开号：US20140154211A1

  公开（公告）日：2014-06-05

  The present invention relates to 2′-Substituted Nucleoside Derivatives of Formula (I): and pharmaceutically acceptable salts thereof, wherein A, B, X, R 1 , R 2 and R 3 are as defined herein. The present invention also relates to compositions comprising at least one 2′-Substituted Nucleoside Derivative, and methods of using the 2′-Substituted Nucleoside Derivatives for treating or preventing HCV infection in a patient.
• US9061041B2
  申请人：——

  公开号：US9061041B2

  公开（公告）日：2015-06-23