phenyl-(methoxy-α,α-cycloleucinyl)-phosphorochloridate | 840506-49-2

• 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: phenyl-(methoxy-α,α-cycloleucinyl)-phosphorochloridate
• 英文别名: Methyl 1-[[chloro(phenoxy)phosphoryl]amino]cyclopentane-1-carboxylate
• CAS: 840506-49-2
• 化学式: C₁₃H₁₇ClNO₄P
• 分子量: 317.709
• InChiKey: LAQMGLXZXQOHGC-UHFFFAOYSA-N

物化性质

• 沸点：
  396.7±44.0 °C(Predicted)
• 密度：
  1.31±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  20
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.46
• 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：

  phenyl-(methoxy-α,α-cycloleucinyl)-phosphorochloridate 、 溴夫定 在 N-甲基咪唑 作用下， 以 四氢呋喃 为溶剂， 以51%的产率得到(E)-5-(2-bromovinyl)-2'-deoxyuridine-5'-[phenyl-(methoxy-α,α-cycloleucinyl)]-phosphate
  参考文献：
  名称：

  Anti-cancer ProTides: tuning the activity of BVDU phosphoramidates related to thymectacin

  摘要：

  Based on our wide ranging knowledge of phosphoramidate ProTides as anti-viral agents we have tuned the lead anti-cancer agent thymectacin in the ester and amino acid regions and revealed a substantial enhancement in in vitro potency versus colon and prostate cancer cell lines. Twelve analogues have been reported, with yields of 29-78%. The compounds are fully characterised and data clearly reveal the presence of two phosphate diastereoisomers, as expected, in roughly equi-molar proportions. The compounds were evaluated in tissue culture versus three different tumour cell lines, using thymectacin as the control. It is notable that minor structural modification of the parent phenyl methoxyalaninyl structure of thymectacin leads to significant enhancements in potency. In particular, replacement of the methyl ester moiety in the lead by a benzyl ester gave a 175-fold boost in potency versus colon cancer HT115. This derivative emerges as a low micromolar inhibitor of HT115 cells and a new lead for further optimisation. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2005.02.041
• 作为产物：
  描述：

  环亮氨酸甲酯盐酸盐 、 二氯磷酸苯酯 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 生成 phenyl-(methoxy-α,α-cycloleucinyl)-phosphorochloridate
  参考文献：
  名称：

  Anti-cancer ProTides: tuning the activity of BVDU phosphoramidates related to thymectacin

  摘要：

  Based on our wide ranging knowledge of phosphoramidate ProTides as anti-viral agents we have tuned the lead anti-cancer agent thymectacin in the ester and amino acid regions and revealed a substantial enhancement in in vitro potency versus colon and prostate cancer cell lines. Twelve analogues have been reported, with yields of 29-78%. The compounds are fully characterised and data clearly reveal the presence of two phosphate diastereoisomers, as expected, in roughly equi-molar proportions. The compounds were evaluated in tissue culture versus three different tumour cell lines, using thymectacin as the control. It is notable that minor structural modification of the parent phenyl methoxyalaninyl structure of thymectacin leads to significant enhancements in potency. In particular, replacement of the methyl ester moiety in the lead by a benzyl ester gave a 175-fold boost in potency versus colon cancer HT115. This derivative emerges as a low micromolar inhibitor of HT115 cells and a new lead for further optimisation. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2005.02.041

文献信息

• CHEMICAL COMPOUNDS
  申请人：NuCana plc

  公开号：EP3486251A1

  公开（公告）日：2019-05-22

  Phosphoramidate derivatives of nucleotides and their use in the treatment of cancer are described. The base moieties of, for example, each of deoxyuridine, cytarabine, gemcitabine and citidine may be substituted at the 5-position. The phosphoramidate moiety has attached to the P atom an aryl-O moiety and an α-amino acid moiety. The α-amino acid moiety may correspond to or be derived from either a naturally occurring or a non-naturally occurring amino acid.

  本文介绍了核苷酸的磷酰胺衍生物及其在治疗癌症中的应用。例如，脱氧尿苷、阿糖胞苷、吉西他滨和枸橼酸的碱基可在 5 位被取代。磷酰胺基团的 P 原子上连接有一个芳基-O 基团和一个α-氨基酸基团。α-氨基酸分子可以是天然氨基酸或非天然氨基酸，也可以来自天然氨基酸。
• Chemical compounds
  申请人：NuCana plc

  公开号：EP2955190B1

  公开（公告）日：2018-03-28
• US7951787B2
  申请人：——

  公开号：US7951787B2

  公开（公告）日：2011-05-31
• USRE47589E1
  申请人：——

  公开号：USRE47589E1

  公开（公告）日：2019-09-03
• Anti-cancer ProTides: tuning the activity of BVDU phosphoramidates related to thymectacin
  作者：Christopher McGuigan、Jean-Christophe Thiery、Felice Daverio、Wen G. Jiang、Gaynor Davies、Malcolm Mason

  DOI：10.1016/j.bmc.2005.02.041

  日期：2005.5

  Based on our wide ranging knowledge of phosphoramidate ProTides as anti-viral agents we have tuned the lead anti-cancer agent thymectacin in the ester and amino acid regions and revealed a substantial enhancement in in vitro potency versus colon and prostate cancer cell lines. Twelve analogues have been reported, with yields of 29-78%. The compounds are fully characterised and data clearly reveal the presence of two phosphate diastereoisomers, as expected, in roughly equi-molar proportions. The compounds were evaluated in tissue culture versus three different tumour cell lines, using thymectacin as the control. It is notable that minor structural modification of the parent phenyl methoxyalaninyl structure of thymectacin leads to significant enhancements in potency. In particular, replacement of the methyl ester moiety in the lead by a benzyl ester gave a 175-fold boost in potency versus colon cancer HT115. This derivative emerges as a low micromolar inhibitor of HT115 cells and a new lead for further optimisation. (c) 2005 Elsevier Ltd. All rights reserved.