| 1412427-08-7

• 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
• CAS: 1412427-08-7
• 化学式: C₄₂H₆₂N₇O₁₆P
• 分子量: 951.965
• InChiKey: AHKNIXQOJCWQGD-AESULHDTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.93
• 重原子数：
  66.0
• 可旋转键数：
  12.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  278.83
• 氢给体数：
  3.0
• 氢受体数：
  20.0

反应信息

• 作为反应物：
  描述：

  在 三氟乙酸 作用下， 反应 4.0h， 生成 (2S)-ethyl 2-((((2R,3R,4R,5R)-5-(2,6-diamino-9H-purin-9-yl)-3,4-dihydroxy-4-methyltetrahydrofuran-2-yl)methoxy)-(phenoxy)phosphorylamino)propanoate
  参考文献：
  名称：

  β-d-2′-C-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

  摘要：

  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.

  DOI：

  10.1021/jm501874e
• 作为产物：
  描述：

  苯酚 在 N-甲基咪唑 、 三乙胺 、 三氯氧磷 作用下， 以 四氢呋喃 、 乙醚 、 二氯甲烷 、 乙腈 为溶剂， 反应 36.0h， 生成
  参考文献：
  名称：

  β-d-2′-C-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

  摘要：

  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.

  DOI：

  10.1021/jm501874e

文献信息

• [EN] PURINE MONOPHOSPHATE PRODRUGS FOR TREATMENT OF VIRAL INFECTIONS<br/>[FR] PROMÉDICAMENTS À BASE DE MONOPHOSPHATE DE PURINE POUR TRAITER LES INFECTIONS VIRALES
  申请人：RFS PHARMA LLC

  公开号：WO2012158811A3

  公开（公告）日：2013-02-28