(2R,3R,4R,5R)-2-(2-amino-6-methoxypurin-9-yl)-5-(dichlorophosphoryloxymethyl)-3-methyloxolane-3,4-diol

• 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,3R,4R,5R)-2-(2-amino-6-methoxypurin-9-yl)-5-(dichlorophosphoryloxymethyl)-3-methyloxolane-3,4-diol
• 化学式: C₁₂H₁₆Cl₂N₅O₆P
• 分子量: 428.169
• InChiKey: FBAFITGOYAKOAD-GSWPYSDESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.5
• 重原子数：
  26
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  155
• 氢给体数：
  3
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  (2R,3R,4R,5R)-2-(2-amino-6-methoxypurin-9-yl)-5-(dichlorophosphoryloxymethyl)-3-methyloxolane-3,4-diol 在 磷酸三乙酯 、 三乙胺 作用下， 反应 1.0h， 生成 propan-2-yl (2R)-3-[[(2R,3R,4R,5R)-5-(2-amino-6-methoxypurin-9-yl)-3,4-dihydroxy-4-methyloxolan-2-yl]methoxy-[[(2S)-1-oxo-1-propan-2-yloxypropan-2-yl]amino]phosphoryl]sulfanyl-2-(methoxycarbonylamino)propanoate
  参考文献：
  名称：

  THIOPHOSPHATE NUCLEOSIDES FOR THE TREATMENT OF HCV

  摘要：

  本文提供了用于治疗黄病毒科感染，包括HCV感染的化合物、组合物和方法。在某些实施例中，所述化合物符合以下公式2001： 其中PD、Base、R A 和R B 如本文所述。在某些实施例中，披露了核苷类衍生物的化合物和组合物，可以单独或与其他抗病毒药物联合使用。

  公开号：

  US20140248242A1
• 作为产物：
  描述：

  2'-C-甲基-6-O-甲基鸟苷 在 磷酸三乙酯 、 三氯氧磷 作用下， 反应 0.5h， 生成 (2R,3R,4R,5R)-2-(2-amino-6-methoxypurin-9-yl)-5-(dichlorophosphoryloxymethyl)-3-methyloxolane-3,4-diol
  参考文献：
  名称：

  THIOPHOSPHATE NUCLEOSIDES FOR THE TREATMENT OF HCV

  摘要：

  本文提供了用于治疗黄病毒科感染，包括HCV感染的化合物、组合物和方法。在某些实施例中，所述化合物符合以下公式2001： 其中PD、Base、R A 和R B 如本文所述。在某些实施例中，披露了核苷类衍生物的化合物和组合物，可以单独或与其他抗病毒药物联合使用。

  公开号：

  US20140248242A1

文献信息

• [EN] PHOSPHORODIAMIDATE DERIVATIVES OF GUANOSINE NUCLEOSIDE COMPOUNDS FOR TREATMENT OF VIRAL INJECTIONS<br/>[FR] DÉRIVÉS PHOSPHORODIAMIDATE DE COMPOSÉS NUCLÉOSIDIQUES À BASE DE GUANOSINE DESTINÉS À TRAITER DES INFECTIONS VIRALES
  申请人：INHIBITEX INC

  公开号：WO2012048013A3

  公开（公告）日：2012-06-14
• US9339541B2
  申请人：——

  公开号：US9339541B2

  公开（公告）日：2016-05-17
• [EN] THIOPHOSPHATE NUCLEOSIDES FOR THE TREATMENT OF HCV<br/>[FR] NUCLÉOSIDES DE THIOPHOSPHATE POUR LE TRAITEMENT DU VHC
  申请人：IDENIX PHARMACEUTICALS INC

  公开号：WO2014137930A1

  公开（公告）日：2014-09-12

  Provided herein are compounds, compositions, and methods for the treatment of Flaviviridae infections, including HCV infections. In certain embodiments, the compounds are according to Formula 2001; where PD, Base, RA and RB are as provided herein. In certain embodiments, compounds and compositions of nucleoside derivatives are disclosed, which can be administered either alone or in combination with other anti-viral agents.
• THIOPHOSPHATE NUCLEOSIDES FOR THE TREATMENT OF HCV
  申请人：IDENIX PHARMACEUTICALS, INC.

  公开号：US20140248242A1

  公开（公告）日：2014-09-04

  Provided herein are compounds, compositions and methods for the treatment of Flaviviridae infections, including HCV infections. In certain embodiments, the compounds are according to Formula 2001: where PD, Base, R A and R B are as provided herein. In certain embodiments, compounds and compositions of nucleoside derivatives are disclosed, which can be administered either alone or in combination with other anti-viral agents.

  本文提供了用于治疗黄病毒科感染，包括HCV感染的化合物、组合物和方法。在某些实施例中，所述化合物符合以下公式2001： 其中PD、Base、R A 和R B 如本文所述。在某些实施例中，披露了核苷类衍生物的化合物和组合物，可以单独或与其他抗病毒药物联合使用。
• Phosphorodiamidates as a Promising New Phosphate Prodrug Motif for Antiviral Drug Discovery: Application to Anti-HCV Agents
  作者：Christopher McGuigan、Karolina Madela、Mohamed Aljarah、Claire Bourdin、Maria Arrica、Emma Barrett、Sarah Jones、Alexander Kolykhalov、Blair Bleiman、K. Dawn Bryant、Babita Ganguly、Elena Gorovits、Geoffrey Henson、Damound Hunley、Jeff Hutchins、Jerry Muhammad、Aleksandr Obikhod、Joseph Patti、C. Robin Walters、Jin Wang、John Vernachio、Changalvala V. S. Ramamurty、Srinivas K. Battina、Stanley Chamberlain

  DOI：10.1021/jm2011673

  日期：2011.12.22

  We herein report phosphorodiamidates as a significant new phosphate prodrug motif. Sixty-seven phosphorodiamidates are reported of two 6-O-alkyl 2'-C-methyl guanosines, with significant variation in the diamidate structure. Both symmetrical and asymmetric phosphorodiamidates are reported, derived from various esterified amino acids, both D and L., and also from various simple amines. All of the compounds were evaluated versus hepatitis C virus in replicon assay, and nanomolar activity levels were observed. Many compounds were noncytotoxic at 100 mu M, leading to high antiviral selectivities. The agents are stable in acidic, neutral, and moderately basic media and in selected biological media but show efficient processing by carboxypeptidases and efficiently yield the free nucleoside monophosphate in cells. On the basis of in vitro data, eight leads were selected for additional in vivo evaluation, with the intent of selecting one candidate for progression toward clinical studies. This phosphorodiamidate prodrug method may have broad application outside of HCV and antivirals as it offers many of the advantages of phosphoramidate ProTides but without the chirality issues present in most cases.