1-[(3aR,4R,6R,6aR)-6-(diethoxyphosphorylmethoxymethyl)-2,2-dimethyl-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxol-4-yl]-1,2,4-triazole-3-carboxamide | 594860-75-0

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 三唑核糖核苷和核糖核苷酸
• 英文名称: 1-[(3aR,4R,6R,6aR)-6-(diethoxyphosphorylmethoxymethyl)-2,2-dimethyl-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxol-4-yl]-1,2,4-triazole-3-carboxamide
• CAS: 594860-75-0
• 化学式: C₁₆H₂₇N₄O₈P
• 分子量: 434.386
• InChiKey: YXXHJMWFGWZDNM-RTWAVKEYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.8
• 重原子数：
  29
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.81
• 拓扑面积：
  146
• 氢给体数：
  1
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  1-[(3aR,4R,6R,6aR)-6-(diethoxyphosphorylmethoxymethyl)-2,2-dimethyl-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxol-4-yl]-1,2,4-triazole-3-carboxamide 在 三甲基溴硅烷 、 DOWEX 50WX₈-100 ion-exchange resin 作用下， 以 甲醇 、 乙腈 为溶剂， 反应 17.0h， 生成 1-[5-O-(dihydroxyphosphinyl)methyl-β-D-ribofuranosyl]-1,2,4-triazole-3-carboxamide
  参考文献：
  名称：

  Synthesis of Azole Nucleoside 5′‐Monophosphate Mimics (P1Ms) and Their Inhibitory Properties of IMP Dehydrogenases

  摘要：

  IMPDH inhibitors have potential antimicrobial, anticancer and immunomodulatory effects. Nucleoside inhibitors of IMPDH exert their inhibitory effects via nucleoside 5'-MPs. Conversion of nucleoside analogs to NMPs by cellular nucleoside kinases is not assured, and usually is inefficient. In order to bypass cellular phosphorylation, a series of azole nucleoside 5'-MP mimics (P1Ms) based on ribavirin, EICAR and bredinin were synthesized and screened against human and C. albicans IMP dehydrogenises. P1Ms 8, 16, 25, 28 and 29 demonstrated substantial IMPDH inhibition with K-i values in low micromolar range.

  DOI：

  10.1081/ncn-120027838
• 作为产物：
  描述：

  三乙酰利巴韦林甲酯 在 高氯酸 、 氨 、 sodium methylate 、 sodium hydride 作用下， 以 四氢呋喃 、 甲醇 、 丙酮 为溶剂， 反应 6.0h， 生成 1-[(3aR,4R,6R,6aR)-6-(diethoxyphosphorylmethoxymethyl)-2,2-dimethyl-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxol-4-yl]-1,2,4-triazole-3-carboxamide
  参考文献：
  名称：

  Synthesis of Azole Nucleoside 5′‐Monophosphate Mimics (P1Ms) and Their Inhibitory Properties of IMP Dehydrogenases

  摘要：

  IMPDH inhibitors have potential antimicrobial, anticancer and immunomodulatory effects. Nucleoside inhibitors of IMPDH exert their inhibitory effects via nucleoside 5'-MPs. Conversion of nucleoside analogs to NMPs by cellular nucleoside kinases is not assured, and usually is inefficient. In order to bypass cellular phosphorylation, a series of azole nucleoside 5'-MP mimics (P1Ms) based on ribavirin, EICAR and bredinin were synthesized and screened against human and C. albicans IMP dehydrogenises. P1Ms 8, 16, 25, 28 and 29 demonstrated substantial IMPDH inhibition with K-i values in low micromolar range.

  DOI：

  10.1081/ncn-120027838

文献信息

• Nucleoside 5'-monophosphate mimics and their prodrugs
  申请人：——

  公开号：US20040023901A1

  公开（公告）日：2004-02-05

  The present invention relates to novel nucleoside 5′-monophosphate mimics, which contain novel nucleoside bases and phosphate moiety mimics optionally having sugar-modifications. The nucleotide mimics of the present invention, in a form of a pharmaceutically acceptable salt, a pharmaceutically acceptable prodrug, or a pharmaceutical formulation, are useful as antiviral, antimicrobial, anticancer, and immunomodulatory agents. The present invention provides a method for the treatment of viral infections, microbial infections, and proliferative disorders. The present invention also relates to pharmaceutical compositions comprising the compounds of the present invention optionally in combination with other pharmaceutically active agents.

  本发明涉及一种新型的核苷酸5'-单磷酸类似物，其中包含新型的核苷酸碱基和磷酸基类似物，可选择具有糖基修饰。本发明的核苷酸类似物以药学可接受的盐、药学可接受的前药或制剂的形式，作为抗病毒、抗微生物、抗癌和免疫调节剂。本发明提供了一种治疗病毒感染、微生物感染和增殖性疾病的方法。本发明还涉及包含本发明化合物的药物组合物，可选择与其他药学活性剂组合使用。
• Synthesis of Azole Nucleoside 5′‐Monophosphate Mimics (P1Ms) and Their Inhibitory Properties of IMP Dehydrogenases
  作者：Guangyi Wang、Kandasamy Sakthivel、Vasanthakumar Rajappan、Thomas W. Bruice、Kathleen Tucker、Patrick Fagan、Jennifer L. Brooks、Tiffany Hurd、Janet M. Leeds、P. Dan Cook

  DOI：10.1081/ncn-120027838

  日期：2004.1.1

  IMPDH inhibitors have potential antimicrobial, anticancer and immunomodulatory effects. Nucleoside inhibitors of IMPDH exert their inhibitory effects via nucleoside 5'-MPs. Conversion of nucleoside analogs to NMPs by cellular nucleoside kinases is not assured, and usually is inefficient. In order to bypass cellular phosphorylation, a series of azole nucleoside 5'-MP mimics (P1Ms) based on ribavirin, EICAR and bredinin were synthesized and screened against human and C. albicans IMP dehydrogenises. P1Ms 8, 16, 25, 28 and 29 demonstrated substantial IMPDH inhibition with K-i values in low micromolar range.