1-naphthyl-(methoxy-L-valinyl)-phosphorochloridate | 874362-18-2

• 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: 1-naphthyl-(methoxy-L-valinyl)-phosphorochloridate
• 英文别名: 1-naphthyl-(methoxy-L-valinyl)phosphochloridate；(2S)-methyl 2-(chloro(naphthalen-1-yloxy)phosphorylamino)-3-methylbutanoate；methyl (2S)-2-[[chloro(naphthalen-1-yloxy)phosphoryl]amino]-3-methylbutanoate
• CAS: 874362-18-2
• 化学式: C₁₆H₁₉ClNO₄P
• 分子量: 355.758
• InChiKey: GORQWXCFVFLUAT-NGMICRHFSA-N

物化性质

• 沸点：
  462.2±47.0 °C(Predicted)
• 密度：
  1.276±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  23
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  64.6
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1-naphthyl-(methoxy-L-valinyl)-phosphorochloridate 、 溴夫定 在 N-甲基咪唑 作用下， 以 四氢呋喃 为溶剂， 反应 12.0h， 以39.8%的产率得到(E)-5-(2-bromovinyl)-2'-deoxyuridine-5'-[1-naphthyl-(methoxy-L-valinyl)]phosphate
  参考文献：
  名称：

  Novel Potential Anticancer Naphthyl Phosphoramidates of BVdU:  Separation of Diastereoisomers and Assignment of the Absolute Configuration of the Phosphorus Center

  摘要：

  We have previously reported our SAR optimization of the anticancer agent thymectacin. Tuning of the parent ProTide structure initially involved the amino acid and, subsequently, the aromatic masking group on the phosphate moiety. Herein, derivatives bearing the combined modifications are reported and biological evaluation is described. Moreover, separation of the diastereoisomeric final product mixture shows a different cytostatic activity for the two diastereoisomers. Through computational and NMR studies, the absolute stereochemistry of the phosphorus center of the two diastereoisomers has been suggested.

  DOI：

  10.1021/jm0509896
• 作为产物：
  描述：

  L-缬氨酸甲酯 、 1-萘基二氯磷酸酯 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 生成 1-naphthyl-(methoxy-L-valinyl)-phosphorochloridate
  参考文献：
  名称：

  Novel Potential Anticancer Naphthyl Phosphoramidates of BVdU:  Separation of Diastereoisomers and Assignment of the Absolute Configuration of the Phosphorus Center

  摘要：

  We have previously reported our SAR optimization of the anticancer agent thymectacin. Tuning of the parent ProTide structure initially involved the amino acid and, subsequently, the aromatic masking group on the phosphate moiety. Herein, derivatives bearing the combined modifications are reported and biological evaluation is described. Moreover, separation of the diastereoisomeric final product mixture shows a different cytostatic activity for the two diastereoisomers. Through computational and NMR studies, the absolute stereochemistry of the phosphorus center of the two diastereoisomers has been suggested.

  DOI：

  10.1021/jm0509896

文献信息

• Phosphoramidate Derivatives of Guanosine Nucleoside Compunds for Treatment of Viral Infections
  申请人：Chamberlain Stanley

  公开号：US20120052046A1

  公开（公告）日：2012-03-01

  Phosphoramidate compounds derived from guanine bases having enhanced therapeutic potency are provided, and these compounds in particular have enhanced potency with respect to treatment of viral infections, such as hepatitis C virus. Pharmaceutical compositions, methods of preparing the compounds, and methods of using the compounds and compositions to treat viral infections are also provided.

  本发明提供了从鸟嘌呤碱基衍生的磷酰胺化合物，具有增强的治疗效力，特别是对于治疗病毒感染，如丙型肝炎病毒，具有增强的效力。本发明还提供了制备该化合物的制药组合物、制备该化合物的方法以及使用该化合物和组合物治疗病毒感染的方法。
• Synthesis and biological evaluation of prodrugs of 2-fluoro-2-deoxyribose-1-phosphate and 2,2-difluoro-2-deoxyribose-1-phosphate
  作者：Nadege Hamon、Maurizio Quintiliani、Jan Balzarini、Christopher McGuigan

  DOI：10.1016/j.bmcl.2013.02.117

  日期：2013.5

  We report in this Letter the synthesis of prodrugs of 2-fluoro-2-deoxyarabinose-1-phosphate and 2,2-difluoro-2-deoxyribose-1-phosphate. We demonstrate the difficulty of realising a phosphorylation step on the anomeric position of 2-deoxyribose, and we discover that introduction of fluorine atoms on the 2 position of 2-deoxyribose enables the phosphorylation step: in fact, the stability of the prodrugs increases with the degree of 2-fluorination. Stability studies of produgs of 2-fluoro-2-deoxyribose-1-phosphate and 2,2-difluoro-2-deoxyribose-1-phosphate in acidic and neutral conditions were conducted to confirm our observation. Biological evaluation of prodrugs of 2,2-difluoro-2-deoxyribose-1-phosphate for antiviral and cytotoxic activity is reported. (C) 2013 Published by Elsevier Ltd.
• The Application of Phosphoramidate Protide Technology to Acyclovir Confers Anti-HIV Inhibition
  作者：Marco Derudas、Davide Carta、Andrea Brancale、Christophe Vanpouille、Andrea Lisco、Leonid Margolis、Jan Balzarini、Christopher McGuigan

  DOI：10.1021/jm9007856

  日期：2009.9.10

  Recently, it has been reported that phosphorylated acyclovir (ACV) inhibits human immunodeficiency virus type 1 (HIV-1) reverse transcriptase in a cell-free system. To deliver phosphorylated ACV inside cells, we designed ACV monophosphorylated derivatives using ProTide technology. We found that the L-alanine derived ProTides show anti-HIV activity at noncytotoxic concentrations; ester and aryl variation was tolerated, ACV ProTides with other amino acids, other than L-phenylalanine, showed no detectable activity against HIV in cell culture. The inhibitory activity of the prodrugs against herpes simplex virus (HSV) types-1 and -2 and thymidine kinase-deficient HSV-1 revealed different structure-activity relationships but was again consistent with successful nucleoside kinase bypass. Enzymatic and molecular modeling studies have been performed in order to better understand the antiviral behavior of these compounds. ProTides showing diminished carboxypeptidase lability translated to poor anti-HIV agents and vice versa, so the assay became predictive.
• PHOSPHORAMIDATE DERIVATIVES OF GUANOSINE NUCLEOSIDE COMPOUNDS FOR TREATMENT OF VIRAL INFECTIONS
  申请人：University College Cardiff Consultants, Ltd.

  公开号：EP2385951A2

  公开（公告）日：2011-11-16
• US8759318B2
  申请人：——

  公开号：US8759318B2

  公开（公告）日：2014-06-24