phenyl (benzoxy-L-prolinyl) phosphorochloridate | 1184942-64-0

• 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 (benzoxy-L-prolinyl) phosphorochloridate
• 英文别名: phenyl-(benzyloxy-L-prolinyl) phosphorochloridate；benzyl (2S)-1-[chloro(phenoxy)phosphoryl]pyrrolidine-2-carboxylate
• CAS: 1184942-64-0
• 化学式: C₁₈H₁₉ClNO₄P
• 分子量: 379.78
• InChiKey: RUDYMKYRDCFTRV-LFUZPPSTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  25
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  55.8
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  phenyl (benzoxy-L-prolinyl) phosphorochloridate 、 5-氟-2'-脱氧脲核苷 在 N-甲基咪唑 作用下， 以 四氢呋喃 为溶剂， 生成 5-fluoro-2'-deoxyuridine-5'-O-[phenyl(benzoxy-L-prolinyl)]phosphate
  参考文献：
  名称：

  Phosphoramidate ProTides of the Anticancer Agent FUDR Successfully Deliver the Preformed Bioactive Monophosphate in Cells and Confer Advantage over the Parent Nucleoside

  摘要：

  The fluorinated pyrimidine family of nucleosides continues to represent major current chemotherapeutic agents for treating solid tumors. We herein report their phosphate prodrugs, ProTides, as promising new derivatives, which partially bypass the dependence of the current drugs on active transport and nucleoside kinase-mediated activation. They are also resistant to metabolic deactivation by phosphorolytic enzymes. We report 39 ProTides of the fluorinated pyrimidine FUDR with variation in the aryl, ester, and amino acid. regions. Notably, only certain ProTide motifs are successful in delivering the nucleoside monophosphate into intact cells. We also find that the ProTides retain activity in mycoplasma infected cells, unlike FUDR. Data suggest these compounds to be worthy of further progression.

  DOI：

  10.1021/jm200815w
• 作为产物：
  描述：

  L-脯氨酸苄酯盐酸盐 、 二氯磷酸苯酯 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 1.5h， 以72%的产率得到phenyl (benzoxy-L-prolinyl) phosphorochloridate
  参考文献：
  名称：

  [EN] PHOSPHORODIAMIDATES AND OTHER PHOSPHORUS DERIVATIVES OF FINGOLIMOD AND RELATED S1 P RECEPTOR MODULATORS
  [FR] PHOSPHORODIAMIDATES ET AUTRES DÉRIVÉS DE PHOSPHORE DE FINGOLIMOD ET MODULATEURS DE RÉCEPTEUR S1 P ASSOCIÉS

  摘要：

  通式（I）的化合物：（式I）其中R1、Q、R3、R4、R5、R6、R7和Ar1的定义如下，是类I组蛋白去乙酰化酶的抑制剂，可用于治疗溶酶体贮积症，特别是尼曼-匹克C型疾病，以及其他溶酶体贮积症、缺陷自噬、游离胆固醇积累和分枝杆菌病。

  公开号：

  WO2019064012A1

文献信息

• [EN] SALTS OF DIPHOSPHATE PHOSPHORAMIDATE OF NUCLEOSIDES AS ANTICANCER COMPOUNDS<br/>[FR] SELS DE PHOSPHORAMIDATE DIPHOSPHATE DE NUCLÉOSIDES UTILISÉS EN TANT QUE COMPOSÉS ANTICANCÉREUX
  申请人：NUCANA PLC

  公开号：WO2019110991A1

  公开（公告）日：2019-06-13

  The present invention relates to compounds comprising a salt of a diphosphate phosphoramidate of a nucleoside drug, e.g. clofarabine. The compounds are useful in the treatment of cancer, e.g. leukemia.

  本发明涉及包括核苷药物的二磷酸磷酰胺盐化合物，例如克洛法滨。这些化合物在癌症治疗中，如白血病治疗中具有用途。
• Phosphorodiamidates and other phosphorus derivatives of fingolimod and related S1P receptor modulators
  申请人：UNIVERSITY COLLEGE CARDIFF CONSULTANTS LTD

  公开号：US11078221B2

  公开（公告）日：2021-08-03

  Compounds of general formula (I): (Formula I)) wherein R1, Q, R3, R4, R5, R6, R7 and Ar1 are as defined herein are inhibitors of class I histone deacetylases and are of use in the treatment of lysosomal storage disorders, especially Niemann-Pick type C disease, as well as other lysosomal storage disorders, defective autophagy, accumulation of free cholesterol and mycobacterial diseases.

  通式(I)的化合物：(式 I)) 其中 R1、Q、R3、R4、R5、R6、R7 和 Ar1 如本文所定义，是 I 类组蛋白去乙酰化酶的抑制剂，可用于治疗溶酶体贮积症，尤其是 C 型尼曼-皮克病，以及其他溶酶体贮积症、自噬缺陷、游离胆固醇积累和霉菌病。
• 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.
• PHOSPHORODIAMIDATES AND OTHER PHOSPHORUS DERIVATIVES OF FINGOLIMOD AND RELATED S1 P RECEPTOR MODULATORS
  申请人：UNIVERSITY COLLEGE CARDIFF CONSULTANTS LTD

  公开号：US20200255460A1

  公开（公告）日：2020-08-13

  Compounds of general formula (I): (Formula I)) wherein R 1 , Q, R 3 , R 4 , R 5 , R 6 , R 7 and Ar 1 are as defined herein are inhibitors of class I histone deacetylases and are of use in the treatment of lysosomal storage disorders, especially Niemann-Pick type C disease, as well as other lysosomal storage disorders, defective autophagy, accumulation of free cholesterol and mycobacterial diseases.
• Phosphoramidate ProTides of the Anticancer Agent FUDR Successfully Deliver the Preformed Bioactive Monophosphate in Cells and Confer Advantage over the Parent Nucleoside
  作者：Christopher McGuigan、Paola Murziani、Magdalena Slusarczyk、Blanka Gonczy、Johan Vande Voorde、Sandra Liekens、Jan Balzarini

  DOI：10.1021/jm200815w

  日期：2011.10.27

  The fluorinated pyrimidine family of nucleosides continues to represent major current chemotherapeutic agents for treating solid tumors. We herein report their phosphate prodrugs, ProTides, as promising new derivatives, which partially bypass the dependence of the current drugs on active transport and nucleoside kinase-mediated activation. They are also resistant to metabolic deactivation by phosphorolytic enzymes. We report 39 ProTides of the fluorinated pyrimidine FUDR with variation in the aryl, ester, and amino acid. regions. Notably, only certain ProTide motifs are successful in delivering the nucleoside monophosphate into intact cells. We also find that the ProTides retain activity in mycoplasma infected cells, unlike FUDR. Data suggest these compounds to be worthy of further progression.