(2R,3S,4S,5R,6R)-2-((R)-2-amino-1-((3aR,4S,6R,6aR)-6-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)-2-oxoethoxy)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triyl triacetate | 1384271-45-7

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (2R,3S,4S,5R,6R)-2-((R)-2-amino-1-((3aR,4S,6R,6aR)-6-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)-2-oxoethoxy)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triyl triacetate
• CAS: 1384271-45-7
• 化学式: C₂₅H₃₃N₃O₁₅
• 分子量: 615.548
• InChiKey: ZQWGIXNAJVILAV-RTXMVLDASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -2.66
• 重原子数：
  43.0
• 可旋转键数：
  9.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.68
• 拓扑面积：
  243.23
• 氢给体数：
  3.0
• 氢受体数：
  16.0

反应信息

• 作为反应物：
  描述：

  (2R,3S,4S,5R,6R)-2-((R)-2-amino-1-((3aR,4S,6R,6aR)-6-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)-2-oxoethoxy)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triyl triacetate 在 N-甲基吗啉 、 sodium chlorite 、 sodium dihydrogenphosphate dihydrate 、 2-甲基-2-丁烯 、 三氧化硫吡啶 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 二氯甲烷 、 水 、 二甲基亚砜 、 N,N-二甲基甲酰胺 、 叔丁醇 为溶剂， 反应 19.0h， 生成 (2S,3S,4S)-2-((R)-2-amino-1-((3aR,4S,6R,6aR)-6-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)-2-oxoethoxy)-6-((4-(4-(4-(trifluoromethoxy)phenoxy)piperidin-1-yl)benzyl)carbamoyl)-3,4-dihydro-2H-pyran-3,4-diyl diacetate
  参考文献：
  名称：

  DPAGT1 Inhibitors of Capuramycin Analogues and Their Antimigratory Activities of Solid Tumors

  摘要：

  Capuramycin displays a narrow spectrum of antibacterial activity by targeting bacterial translocase I (MraY). In our program of development of new N-acetylglucosaminephosphotransferase1 (DPAGT1) inhibitors, we have identified that a capuramycin phenoxypiperidinylbenzylamide analogue (CPPB) inhibits DPAGT1 enzyme with an IC50 value of 200 nM. Despite a strong DPAGT1 inhibitory activity, CPPB does not show cytotoxicity against normal cells and a series of cancer cell lines. However, CPPB inhibits migrations of several solid cancers including pancreatic cancers that require high DPAGT1 expression in order for tumor progression. DPAGT1 inhibition by CPPB leads to a reduced expression level of Snail but does not reduce E-cadherin expression level at the IC50 (DPAGT1) concentration. CPPB displays a strong synergistic effect with paclitaxel against growthinhibitory action of a patient-derived pancreatic adenocarcinoma, PD002: paclitaxel (IC50: 1.25 mu M) inhibits growth of PD002 at 0.0024-0.16 mu M in combination with 0.10-2.0 mu M CPPB (IC50: 35 mu M).

  DOI：

  10.1021/acs.jmedchem.0c00545
• 作为产物：
  描述：

  在 strontium(II) carbonate 、 N-碘代丁二酰亚胺 、 silver tetrafluoroborate 、 乙醛肟 、 palladium 10% on activated carbon 、 氢气 、 溶剂黄146 、 硫脲 、 mercury dichloride 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 二氯甲烷 、 水 、 异丙醇 为溶剂， 反应 48.0h， 生成 (2R,3S,4S,5R,6R)-2-((R)-2-amino-1-((3aR,4S,6R,6aR)-6-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)-2-oxoethoxy)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triyl triacetate
  参考文献：
  名称：

  DPAGT1 Inhibitors of Capuramycin Analogues and Their Antimigratory Activities of Solid Tumors

  摘要：

  Capuramycin displays a narrow spectrum of antibacterial activity by targeting bacterial translocase I (MraY). In our program of development of new N-acetylglucosaminephosphotransferase1 (DPAGT1) inhibitors, we have identified that a capuramycin phenoxypiperidinylbenzylamide analogue (CPPB) inhibits DPAGT1 enzyme with an IC50 value of 200 nM. Despite a strong DPAGT1 inhibitory activity, CPPB does not show cytotoxicity against normal cells and a series of cancer cell lines. However, CPPB inhibits migrations of several solid cancers including pancreatic cancers that require high DPAGT1 expression in order for tumor progression. DPAGT1 inhibition by CPPB leads to a reduced expression level of Snail but does not reduce E-cadherin expression level at the IC50 (DPAGT1) concentration. CPPB displays a strong synergistic effect with paclitaxel against growthinhibitory action of a patient-derived pancreatic adenocarcinoma, PD002: paclitaxel (IC50: 1.25 mu M) inhibits growth of PD002 at 0.0024-0.16 mu M in combination with 0.10-2.0 mu M CPPB (IC50: 35 mu M).

  DOI：

  10.1021/acs.jmedchem.0c00545

文献信息

• [EN] DPAGT1 INHIBITORS OF CAPURAMYCIN ANALOGUES AND THEIR ANTIMIGRATORY ACTIVITIES OF SOLID TUMORS<br/>[FR] INHIBITEURS DE DPAGT1 D'ANALOGUES DE CAPURAMYCINE ET LEURS ACTIVITÉS ANTIMIGRATOIRES DE TUMEURS SOLIDES
  申请人：UNIV TENNESSEE RES FOUND

  公开号：WO2022006231A1

  公开（公告）日：2022-01-06

  Provided herein are compounds and methods of using these compounds to treat disorders related to DPAGT1 function, including cancer and bacterial infections.

  本文提供了化合物及其使用方法，用于治疗与DPAGT1功能相关的疾病，包括癌症和细菌感染。
• A reliable Pd-mediated hydrogenolytic deprotection of BOM group of uridine ureido nitrogen
  作者：Bilal A. Aleiwi、Michio Kurosu

  DOI：10.1016/j.tetlet.2012.05.035

  日期：2012.7

  The benzyloxymethyl (BOM) group has been utilized widely in syntheses of a variety of natural and non-natural products. The BOM group is also one of few choices to protect uridine ureido nitrogen. However, hydrogenolytic cleavage of the BOM group of uridine derivatives has been unreliably performed via heterogeneous conditions using Pd catalysts. One of the undesirable by-products formed by Pd-mediated hydrogenation conditions is the over-reduced product in which the C5-C6 double bond of the uracil moiety was saturated. To date, we have generated a wide range of uridine-containing antibacterial agents, where the BOM group has been utilized in their syntheses. In screening of deprotection conditions of the BOM group of uridine ureido nitrogen under Pd-mediated hydrogenation conditions, we realized that the addition of water to the (PrOH)-Pr-i-based hydrogenation conditions can suppress the formation of over-reduced uridine derivatives and the addition of HCO2H (0.5%) dramatically improve the reaction rate. An optimized hydrogenation condition described here can be applicable to the BOM-deprotections of a wide range of uridine derivatives. (C) 2012 Elsevier Ltd. All rights reserved.