N'-[1-[(2R,3S,4S,5R)-5-azido-4-hydroxy-5-(hydroxymethyl)-3-methyloxolan-2-yl]-2-oxopyrimidin-4-yl]-N,N-dimethylmethanimidamide | 1019639-25-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: N'-[1-[(2R,3S,4S,5R)-5-azido-4-hydroxy-5-(hydroxymethyl)-3-methyloxolan-2-yl]-2-oxopyrimidin-4-yl]-N,N-dimethylmethanimidamide
• CAS: 1019639-25-8
• 化学式: C₁₃H₁₉N₇O₄
• 分子量: 337.338
• InChiKey: GEMRIYDCFZANKS-MVVXRAEJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.2
• 重原子数：
  24
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  112
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  N'-[1-[(2R,3S,4S,5R)-5-azido-4-hydroxy-5-(hydroxymethyl)-3-methyloxolan-2-yl]-2-oxopyrimidin-4-yl]-N,N-dimethylmethanimidamide 在 N-甲基咪唑 、 盐酸 作用下， 以 四氢呋喃 、 水 、 乙腈 为溶剂， 生成
  参考文献：
  名称：

  Discovery of 4′-azido-2′-deoxy-2′-C-methyl cytidine and prodrugs thereof: A potent inhibitor of Hepatitis C virus replication

  摘要：

  4'-Azido-2'-deoxy-2'-methylcytidine (14) is a potent nucleoside inhibitor of the HCV NS5B RNA-dependent RNA polymerase, displaying an EC50 value of 1.2 mu M and showing moderate in vivo bioavailability in rat (F = 14%). Here we describe the synthesis and biological evaluation of 4'-azido-2'-deoxy-2'-methylcytidine and prodrug derivatives thereof. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.03.021
• 作为产物：
  描述：

  1-[(2R,3S,4S,5S)-4-hydroxy-5-(iodomethyl)-3-methyloxolan-2-yl]pyrimidine-2,4-dione 在 吡啶 、 四氮唑 、 4-二甲氨基吡啶 、 硫酸氢铵 、 benzyl triethylammonium azide 、 氨 、 碘 、 sodium methylate 、 2-chlorophenylphosphoryl dichloride 、 N-甲基吗啉氧化物 、 间氯过氧苯甲酸 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 N-甲基吡咯烷酮 、 甲醇 、 二氯甲烷 为溶剂， 生成 N'-[1-[(2R,3S,4S,5R)-5-azido-4-hydroxy-5-(hydroxymethyl)-3-methyloxolan-2-yl]-2-oxopyrimidin-4-yl]-N,N-dimethylmethanimidamide
  参考文献：
  名称：

  Discovery of 4′-azido-2′-deoxy-2′-C-methyl cytidine and prodrugs thereof: A potent inhibitor of Hepatitis C virus replication

  摘要：

  4'-Azido-2'-deoxy-2'-methylcytidine (14) is a potent nucleoside inhibitor of the HCV NS5B RNA-dependent RNA polymerase, displaying an EC50 value of 1.2 mu M and showing moderate in vivo bioavailability in rat (F = 14%). Here we describe the synthesis and biological evaluation of 4'-azido-2'-deoxy-2'-methylcytidine and prodrug derivatives thereof. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.03.021

文献信息

• Phosphoramidate Derivatives of Nucleosides
  申请人：Centocor Ortho Biotech Products L.P.

  公开号：EP2166016A1

  公开（公告）日：2010-03-24

  Compounds of formula I : R1 is hydrogen, C1-C4alkyl, OH, C1-C4alkoxy; R2 is phenyl, optionally substituted with 1, 2 or 3 substituents each independently selected from halo, C1-C6alkyl, and C1-C6alkoxy, or R2 is naphtalenyl; R3 is hydrogen, C1-C6alkyl, benzyl; R4 is hydrogen, C1-C6alkyl, benzyl; or R3 and R4 together with the carbon atom to which they are attached form C3-C7cycloalkyl; R5 is C1-C6alkyl, benzyl, or phenyl, optionally substituted with 1, 2 or 3 substituents each independently selected from hydroxy, C1-C6alkoxy, amino, mono- and diC1-C6alkylamino; or a pharmaceutically acceptable salt or solvate thereof; useful in the prophylaxis or treatment of HCV infections.

  公式I的化合物：R1是氢、C1-C4烷基、羟基、C1-C4烷氧基；R2是苯基，可选地取代有1、2或3个取代基，每个取代基独立选择自卤素、C1-C6烷基和C1-C6烷氧基，或者R2是萘基；R3是氢、C1-C6烷基、苄基；R4是氢、C1-C6烷基、苄基；或者R3和R4与它们连接的碳原子一起形成C3-C7环烷基；R5是C1-C6烷基、苄基或苯基，可选地取代有1、2或3个取代基，每个取代基独立选择自羟基、C1-C6烷氧基、氨基、单烷基和双烷基氨基；或其药学上可接受的盐或溶剂；用于预防或治疗丙型肝炎感染。
• Discovery of 4′-azido-2′-deoxy-2′-C-methyl cytidine and prodrugs thereof: A potent inhibitor of Hepatitis C virus replication
  作者：Magnus Nilsson、Genadiy Kalayanov、Anna Winqvist、Pedro Pinho、Christian Sund、Xiao-Xiong Zhou、Horst Wähling、Anna-Karin Belfrage、Michael Pelcman、Tatiana Agback、Kurt Benckestock、Kristina Wikström、Mirva Boothee、Anneli Lindqvist、Christina Rydegård、Tim H.M. Jonckers、Koen Vandyck、Pierre Raboisson、Tse-I Lin、Sophie Lachau-Durand、Herman de Kock、David B. Smith、Joseph A. Martin、Klaus Klumpp、Kenneth Simmen、Lotta Vrang、Ylva Terelius、Bertil Samuelsson、Åsa Rosenquist、Nils Gunnar Johansson

  DOI：10.1016/j.bmcl.2012.03.021

  日期：2012.5

  4'-Azido-2'-deoxy-2'-methylcytidine (14) is a potent nucleoside inhibitor of the HCV NS5B RNA-dependent RNA polymerase, displaying an EC50 value of 1.2 mu M and showing moderate in vivo bioavailability in rat (F = 14%). Here we describe the synthesis and biological evaluation of 4'-azido-2'-deoxy-2'-methylcytidine and prodrug derivatives thereof. (C) 2012 Elsevier Ltd. All rights reserved.