benzyl (2S)-(((2R,3R,4R,5R)-5-(2-amino-6-methoxy-9H-purin-9-yl)-3,4-dihydroxy-4-methyltetrahydrofuran-2-yl)methoxy(naphthalene-1-yloxy)phosphorylamino)propanoate | 1234490-75-5

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: benzyl (2S)-(((2R,3R,4R,5R)-5-(2-amino-6-methoxy-9H-purin-9-yl)-3,4-dihydroxy-4-methyltetrahydrofuran-2-yl)methoxy(naphthalene-1-yloxy)phosphorylamino)propanoate
• 英文别名: Benzyl (2S)-2-{[{[(2R,3R,4R,5R)-5-(2-amino-6-methoxy-9H-purin-9-yl)-3,4-dihydroxy-4-methyltetrahydrofuran-2-yl]methoxy}(naphthalen-1-yloxy)phosphoryl]amino}propanoate；benzyl (2S)-2-[[[(2R,3R,4R,5R)-5-(2-amino-6-methoxypurin-9-yl)-3,4-dihydroxy-4-methyloxolan-2-yl]methoxy-naphthalen-1-yloxyphosphoryl]amino]propanoate
• CAS: 1234490-75-5
• 化学式: C₃₂H₃₅N₆O₉P
• 分子量: 678.638
• InChiKey: SPVHFDYIGLHCIH-WHHJPMMWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  48
• 可旋转键数：
  13
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  202
• 氢给体数：
  4
• 氢受体数：
  14

反应信息

• 作为产物：
  描述：

  1-naphthyl(benzoxy-L-alaninyl)-phosphorochloridate 、 2'-C-甲基-6-O-甲基鸟苷 在 N-甲基咪唑 作用下， 以 四氢呋喃 为溶剂， 以28%的产率得到benzyl (2S)-(((2R,3R,4R,5R)-5-(2-amino-6-methoxy-9H-purin-9-yl)-3,4-dihydroxy-4-methyltetrahydrofuran-2-yl)methoxy(naphthalene-1-yloxy)phosphorylamino)propanoate
  参考文献：
  名称：

  [EN] PHOSPHORAMIDATE DERIVATIVES OF GUANOSINE NUCLEOSIDE COMPOUNDS FOR TREATMENT OF VIRAL INFECTIONS
  [FR] DÉRIVÉS DE PHOSPHORAMIDATE DE COMPOSÉS GUANOSINE NUCLÉOSIDE POUR LE TRAITEMENT D'INFECTIONS VIRALES

  摘要：

  公开号：

  WO2010081082A3

文献信息

• [EN] PHOSPHORAMIDATE DERIVATIVES OF GUANOSINE NUCLEOSIDE COMPOUNDS FOR TREATMENT OF VIRAL INFECTIONS<br/>[FR] DÉRIVÉS DE PHOSPHORAMIDATE DE COMPOSÉS GUANOSINE NUCLÉOSIDE POUR LE TRAITEMENT D'INFECTIONS VIRALES
  申请人：UNIV CARDIFF

  公开号：WO2010081082A3

  公开（公告）日：2010-11-25
• Design, synthesis and evaluation of a novel double pro-drug: INX-08189. A new clinical candidate for hepatitis C virus
  作者：Christopher McGuigan、Karolina Madela、Mohamed Aljarah、Arnaud Gilles、Andrea Brancale、Nicola Zonta、Stanley Chamberlain、John Vernachio、Jeff Hutchins、Andrea Hall、Brenda Ames、Elena Gorovits、Babita Ganguly、Alexander Kolykhalov、Jin Wang、Jerry Muhammad、Joseph M. Patti、Geoffrey Henson

  DOI：10.1016/j.bmcl.2010.06.094

  日期：2010.8

  We herein report a novel double pro-drug approach applied to the anti-HCV agent 2'-beta-C-methyl guanosine. A phosphoramidate ProTide motif and a 6-O-methoxy base pro-drug moiety are combined to generate lipophilic prodrugs of the monophosphate of the guanine nucleoside. Modi. cation of the ester and amino acid moieties lead to a compound INX-08189 that exhibits 10 nM potency in the HCV genotype 1b subgenomic replicon, thus being 500 times more potent than the parent nucleoside. The potency of the lead compound INX-08189 was shown to be consistent with intracellular 2'-C-methyl guanosine triphosphate levels in primary human hepatocytes. The separated diastereomers of INX-08189 were shown to have similar activity in the replicon assay and were also shown to be similar substrates for enzyme processing. INX-08189 has completed investigational new drug enabling studies and has been progressed into human clinical trials for the treatment of chronic HCV infection. (c) 2010 Elsevier Ltd. All rights reserved.