methyl 2-((chloro(naphthalen-1-yloxy)phosphoryl)amino)-2-methylpropanoate | 874362-13-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: methyl 2-((chloro(naphthalen-1-yloxy)phosphoryl)amino)-2-methylpropanoate
• 英文别名: 1-naphthyl-(methoxy-dimethylglycinyl)phosphochloridate；Methyl 2-[[chloro(naphthalen-1-yloxy)phosphoryl]amino]-2-methylpropanoate
• CAS: 874362-13-7
• 化学式: C₁₅H₁₇ClNO₄P
• 分子量: 341.731
• InChiKey: KEPOKLIYISOMKE-UHFFFAOYSA-N

物化性质

• 沸点：
  450.5±47.0 °C(Predicted)
• 密度：
  1.307±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  22
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.27
• 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：

  methyl 2-((chloro(naphthalen-1-yloxy)phosphoryl)amino)-2-methylpropanoate 、 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6.5%的产率得到(E)-5-(2-bromovinyl)-2'-deoxyuridine-5'-[1-naphthyl-(methoxy-dimethylglycinyl)]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：

  1-萘基二氯磷酸酯 、 2-氨基异丁酸甲酯盐酸盐 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 生成 methyl 2-((chloro(naphthalen-1-yloxy)phosphoryl)amino)-2-methylpropanoate
  参考文献：
  名称：

  Phosphoramidate and phosphate prodrugs of (−)-β-d-(2R,4R)-dioxolane-thymine: Synthesis, anti-HIV activity and stability studies

  摘要：

  A series of phosphoramidate and phosphate prodrugs of DOT were synthesized via dichlorophosphate or H-phosphonate chemistry and evaluated for their anti-HIV activity against LAI M 184V mutants in PBM cells as well as for their cytotoxicity. The antiviral and cytotoxic profiles of the prodrugs were compared with that of the parent compound (DOT), and it was found that four aryl phosphoramidates 5, 18, 20, and 26 showed a significant enhancement (8- to 12-fold) in anti-HIV activity without cytotoxicity. Chemical stability of these prodrugs was evaluated in phosphate buffer at pH values of biological relevance (i.e., pH 2.0 and 7.4). Enzymatic hydrolysis was also studied in esterase or lipase in buffer solution. Chemical stability studies indicate that the phosphoramidates have good chemical stability at pH 2.0 and at pH 7.4 phosphate buffer. Phosphoramidate prodrugs were hydrolyzed in vitro by esterase or lipase and found to be better substrates for lipases than for esterases. 1,3-Diol cyclic phosphates showed potent anti-HIV activity without increasing the cytotoxicity compared with that of DOT and have good chemical and enzymatic stability. Long-chain lipid phosphates, although showed potent anti-HIV activity, exhibited increased cytotoxicity. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2005.11.008

文献信息

• [EN] NEW 2' AND/OR 5' AMINO-ACID ESTER PHOSPHORAMIDATE 3'-DEOXY ADENOSINE DERIVATIVES AS ANTI-CANCER COMPOUNDS<br/>[FR] NOUVEAUX DÉRIVÉS DE 3'-DÉSOXYADÉNOSINE PRÉSENTANT UN FRAGMENT ESTER DE PHOSPHORAMIDATE ET D'ACIDE AMINÉ 2' ET/OU 5' COMME COMPOSÉS ANTICANCÉREUX
  申请人：NUCANA BIOMED LTD

  公开号：WO2016083830A1

  公开（公告）日：2016-06-02

  The present invention relates to chemical compounds, the compounds for use in a method of treatment, particularly in a method of prophylaxis or treatment for cancer, a process for preparation of the compounds and pharmaceutical compositions comprising the compounds. The compounds may, in particular, be useful in the treatment of leukaemia, lymphoma and/or solid tumours inhomo sapiens. The compounds are derivatives of cordycepin (3'-deoxyadenosine) having a 2' and/or 5'- amino-acid ester phosphoramidate moeity.

  本发明涉及化合物，这些化合物用于治疗方法，特别是用于癌症的预防或治疗方法，以及制备这些化合物的过程和包含这些化合物的药物组合物。这些化合物可能特别适用于治疗人类的白血病、淋巴瘤和/或实体肿瘤。这些化合物是科迪西平（3'-去氧腺苷）的衍生物，具有2'和/或5'-氨基酸酯磷酰胺基团。
• 2′ and/or 5′ amino-acid ester phosphoramidate 3′-deoxy adenosine derivatives as anti- cancer compounds
  申请人：NuCana plc

  公开号：US10570168B2

  公开（公告）日：2020-02-25

  Disclosed are chemical compounds, the compounds for use in a method of treatment, particularly in a method of prophylaxis or treatment for cancer, a process for preparation of the compounds and pharmaceutical compositions comprising the compounds. The compounds may, in particular, be useful in the treatment of leukaemia, lymphoma and/or solid tumours in homo sapiens. The compounds are derivatives of cordycepin (3′-deoxyadenosine) having a 2′ and/or 5′-amino-acid ester phosphoramidate moiety.

  本发明公开了化合物、用于治疗方法（尤其是用于预防或治疗癌症的方法）的化合物、制备化合物的工艺以及包含化合物的药物组合物。这些化合物尤其可用于治疗人类的白血病、淋巴瘤和/或实体瘤。这些化合物是虫草素（3′-脱氧腺苷）的衍生物，具有 2′和/或 5′-氨基酸酯磷酰胺分子。
• 2′ and/or 5′ amino-acid ester phosphoramidate 3′-deoxy adenosine derivatives as anti-cancer compounds
  申请人：NuCana plc

  公开号：US11352387B2

  公开（公告）日：2022-06-07

  Disclosed are chemical compounds, the compounds for use in a method of treatment, particularly in a method of prophylaxis or treatment for cancer, a process for preparation of the compounds and pharmaceutical compositions comprising the compounds. The compounds may, in particular, be useful in the treatment of leukaemia, lymphoma and/or solid tumours in Homo sapiens. The compounds are derivatives of cordycepin (3′-deoxyadenosine) having a 2′ and/or 5′-amino-acid ester phosphoramidate moiety.

  本发明公开了化合物、用于治疗方法（尤其是用于预防或治疗癌症的方法）的化合物、制备化合物的工艺以及包含化合物的药物组合物。这些化合物尤其可用于治疗智人的白血病、淋巴瘤和/或实体瘤。这些化合物是虫草素（3′-脱氧腺苷）的衍生物，具有 2′和/或 5′-氨基酸酯磷酰胺分子。
• NEW 2' AND/OR 5' AMINO-ACID ESTER PHOSPHORAMIDATE 3'-DEOXY ADENOSINE DERIVATIVES AS ANTI-CANCER COMPOUNDS
  申请人：NuCana BioMed Limited

  公开号：EP3224268A1

  公开（公告）日：2017-10-04
• 2' AND/OR 5' AMINO-ACID ESTER PHOSPHORAMIDATE 3'-DEOXY ADENOSINE DERIVATIVES AS ANTI-CANCER COMPOUNDS
  申请人：NuCana Biomed Limited

  公开号：US20170253629A1

  公开（公告）日：2017-09-07

  Disclosed are chemical compounds, the compounds for use in a method of treatment, particularly in a method of prophylaxis or treatment for cancer, a process for preparation of the compounds and pharmaceutical compositions comprising the compounds. The compounds may, in particular, be useful in the treatment of leukaemia, lymphoma and/or solid tumours in homo sapiens . The compounds are derivatives of cordycepin (3′-deoxyadenosine) having a 2′ and/or 5′-amino-acid ester phosphoramidate moiety.