(2R,5R)-2-(3-((benzyloxy)methyl)-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-5-((R)-cyano(hydroxy)methyl)-4-methoxytetrahydrofuran-3-yl acetate | 1158951-49-5

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (2R,5R)-2-(3-((benzyloxy)methyl)-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-5-((R)-cyano(hydroxy)methyl)-4-methoxytetrahydrofuran-3-yl acetate
• 英文别名: 3-[(benzyloxy)methyl]-1-(2-O-acetyl-5-(R)-cayno-3-O-methyl-β-D-ribofuranosyl)uracil；[(2R,3R,4R,5R)-5-[(R)-cyano(hydroxy)methyl]-2-[2,4-dioxo-3-(phenylmethoxymethyl)pyrimidin-1-yl]-4-methoxyoxolan-3-yl] acetate
• CAS: 1158951-49-5
• 化学式: C₂₁H₂₃N₃O₈
• 分子量: 445.429
• InChiKey: JBLHEEBYCNRIIR-YHUYVZNPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.3
• 重原子数：
  32
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  139
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  (2R,5R)-2-(3-((benzyloxy)methyl)-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-5-((R)-cyano(hydroxy)methyl)-4-methoxytetrahydrofuran-3-yl acetate 、 氯乙酸 在 吡啶 、 偶氮二甲酸二异丙酯 、 三苯基膦 作用下， 以 甲苯 为溶剂， 反应 4.0h， 生成 C₂₃H₂₄ClN₃O₉
  参考文献：
  名称：

  Concise Synthesis of Capuramycin

  摘要：

  A concise total synthesis of capuramycin (1), a promising preclinical TB drug lead, is achieved by high-yield formations of the cyanohydrin 5a and 4 '',5 ''-glycal derivative 12. Capuramycin can be synthesized in eight steps from the uridine building block 5a with >30% overall yield. The synthetic intermediates reported here are useful for generation of analogs to improve pharmacokinetic properties of capuramycin.

  DOI：

  10.1021/ol900458w
• 作为产物：
  描述：

  C₂₄H₃₁N₃O₈Si 在 溶剂黄146 作用下， 以 水 为溶剂， 反应 1.0h， 以60%的产率得到(2R,5R)-2-(3-((benzyloxy)methyl)-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-5-((S)-cyano(hydroxy)methyl)-4-methoxytetrahydrofuran-3-yl acetate
  参考文献：
  名称：

  Concise Synthesis of Capuramycin

  摘要：

  A concise total synthesis of capuramycin (1), a promising preclinical TB drug lead, is achieved by high-yield formations of the cyanohydrin 5a and 4 '',5 ''-glycal derivative 12. Capuramycin can be synthesized in eight steps from the uridine building block 5a with >30% overall yield. The synthetic intermediates reported here are useful for generation of analogs to improve pharmacokinetic properties of capuramycin.

  DOI：

  10.1021/ol900458w

文献信息

• DPAGT1 Inhibitors of Capuramycin Analogues and Their Antimigratory Activities of Solid Tumors
  作者：Katsuhiko Mitachi、Rita G. Kansal、Kirk E. Hevener、Cody D. Gillman、Syed M. Hussain、Hyun Gi Yun、Gustavo A. Miranda-Carboni、Evan S. Glazer、William M. Clemons、Michio Kurosu

  DOI：10.1021/acs.jmedchem.0c00545

  日期：2020.10.8

  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).