isopropyl 3-(2-(((S)-(((2R,3R,4R,5R)-5-(2,6-diamino-9H-purin-9-yl)-3,4-dihydroxy-4-methyltetrahydrofuran-2-yl)methoxy)-(((S)-1-isopropoxy-1-oxopropan-2-yl)amino)phosphoryl)oxy)-phenyl)propanoate | 1412427-33-8

• 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: isopropyl 3-(2-(((S)-(((2R,3R,4R,5R)-5-(2,6-diamino-9H-purin-9-yl)-3,4-dihydroxy-4-methyltetrahydrofuran-2-yl)methoxy)-(((S)-1-isopropoxy-1-oxopropan-2-yl)amino)phosphoryl)oxy)-phenyl)propanoate
• 英文别名: propan-2-yl (2S)-2-[[[(2R,3R,4R,5R)-5-(2,6-diaminopurin-9-yl)-3,4-dihydroxy-4-methyloxolan-2-yl]methoxy-[2-(3-oxo-3-propan-2-yloxypropyl)phenoxy]phosphoryl]amino]propanoate
• CAS: 1412427-33-8
• 化学式: C₂₉H₄₂N₇O₁₀P
• 分子量: 679.667
• InChiKey: YYOSDGKUBJESAA-NJXRWUIKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  47
• 可旋转键数：
  16
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  246
• 氢给体数：
  5
• 氢受体数：
  16

反应信息

• 作为产物：
  描述：

  propan-2-yl (2S)-2-[[chloro-[2-(3-oxo-3-propan-2-yloxypropyl)phenoxy]phosphoryl]amino]propanoate 在 10 wt% Pd(OH)2 on carbon N-甲基咪唑 、 sodium azide 、 氢气 、 tetra(tert-butyl)ammonium iodide 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 、 异丙醇 、 乙腈 为溶剂， 反应 13.5h， 生成 isopropyl 3-(2-(((R)-(((2R,3R,4R,5R)-5-(2,6-diamino-9H-purin-9-yl)-3,4-dihydroxy-4-methyltetrahydrofuran-2-yl)methoxy)(((S)-1-isopropoxy-1-oxopropan-2-yl)amino)phosphoryl)oxy)phenyl)propanoate 、 isopropyl 3-(2-(((S)-(((2R,3R,4R,5R)-5-(2,6-diamino-9H-purin-9-yl)-3,4-dihydroxy-4-methyltetrahydrofuran-2-yl)methoxy)-(((S)-1-isopropoxy-1-oxopropan-2-yl)amino)phosphoryl)oxy)-phenyl)propanoate
  参考文献：
  名称：

  [EN] PURINE MONOPHOSPHATE PRODRUGS FOR TREATMENT OF VIRAL INFECTIONS
  [FR] PROMÉDICAMENTS À BASE DE MONOPHOSPHATE DE PURINE POUR TRAITER LES INFECTIONS VIRALES

  摘要：

  公开号：

  WO2012158811A3

文献信息

• β-<scp>d</scp>-2′-<i>C</i>-Methyl-2,6-diaminopurine Ribonucleoside Phosphoramidates are Potent and Selective Inhibitors of Hepatitis C Virus (HCV) and Are Bioconverted Intracellularly to Bioactive 2,6-Diaminopurine and Guanosine 5′-Triphosphate Forms
  作者：Longhu Zhou、Hong-wang Zhang、Sijia Tao、Leda Bassit、Tony Whitaker、Tamara R. McBrayer、Maryam Ehteshami、Sheida Amiralaei、Ugo Pradere、Jong Hyun Cho、Franck Amblard、Drew Bobeck、Mervi Detorio、Steven J. Coats、Raymond F. Schinazi

  DOI：10.1021/jm501874e

  日期：2015.4.23

  The conversion of selected beta-d-2,6-diaminopurine nucleosides (DAPNs) to their phosphoramidate prodrug (PD) substantially blocks the conversion to the G-analog allowing for the generation of two bioactive nucleoside triphosphates (NTPs) in human hepatocytes. A variety of 2'-C-methyl DAPN-PDs were prepared and evaluated for inhibition of HCV viral replication in Huh-7 cells, cytotoxicity in various cell lines, and cellular pharmacology in both Huh-7 and primary human liver cells. The DAPN-PDs were pan-genotypic, effective against various HCV resistant mutants, and resistant variants could not be selected. 2'-C-Me-DAPN-TP and 2'-C-Me-GTP were chain terminators for genotype 1b HCV-pol, and single nucleotide incorporation assays revealed that 2'-C-Me-DAPN-TP was incorporated opposite U. No cytotoxicity was observed with our DAPN-PD when tested up to 50 mu M. A novel, DAPN-PD, 15c, has been selected for further evaluation because of its good virologic and toxicologic profile and its ability to deliver two active metabolites, potentially simplifying HCV treatment.