5-ethynyl-1-(2,3-O-isopropylidene-β-D-ribofuranosyl)imidazole-4-carboxamide | 182494-77-5

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 咪唑核糖核苷和核糖核苷酸
• 英文名称: 5-ethynyl-1-(2,3-O-isopropylidene-β-D-ribofuranosyl)imidazole-4-carboxamide
• 英文别名: 1-[(3aR,4R,6R,6aR)-6-(hydroxymethyl)-2,2-dimethyl-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxol-4-yl]-5-ethynylimidazole-4-carboxamide
• CAS: 182494-77-5
• 化学式: C₁₄H₁₇N₃O₅
• 分子量: 307.306
• InChiKey: MAQURKOPSFGVCS-UORFTKCHSA-N

物化性质

• 沸点：
  583.3±50.0 °C(Predicted)
• 密度：
  1.52±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -1.1
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  109
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  5-ethynyl-1-(2,3-O-isopropylidene-β-D-ribofuranosyl)imidazole-4-carboxamide 在 三氟乙酸 作用下， 反应 0.17h， 以80%的产率得到5-ethynyl-1-β-D-ribofuranosylimidazole-4-carboxamide
  参考文献：
  名称：

  Syntheses of [2-2H]-5-ethynyl-1-(β-D-ribofuranosyl)imidazole-4-carboxamide and 5-ethynyl-1-([5-3H]-β-D-ribofuranosyl)imidazole-4-carboxamide (EICAR)

  摘要：

  DOI：

  10.1002/(sici)1099-1344(199609)38:9<809::aid-jlcr899>3.0.co;2-0
• 作为产物：
  描述：

  5-iodo-1-(5-O-acetyl-2,3-O-isopropylidene-β-D-ribofuranosyl)imidazole-4-carboxamide 在 二氯乙酸 、 ammonium hydroxide 、 sodium tetrahydroborate 、 二(氰基苯)二氯化钯 、 DIAION PK₂₁₂ 、 氨 、 水 、 双氧水 、 草酸 、 三乙胺 、 N,N'-二环己基碳二亚胺 、 三氯氧磷 作用下， 以 甲醇 、 二氯甲烷 、 水 、 二甲基亚砜 、 乙腈 为溶剂， 反应 23.0h， 生成 5-ethynyl-1-(2,3-O-isopropylidene-β-D-ribofuranosyl)imidazole-4-carboxamide
  参考文献：
  名称：

  Syntheses of [2-2H]-5-ethynyl-1-(β-D-ribofuranosyl)imidazole-4-carboxamide and 5-ethynyl-1-([5-3H]-β-D-ribofuranosyl)imidazole-4-carboxamide (EICAR)

  摘要：

  DOI：

  10.1002/(sici)1099-1344(199609)38:9<809::aid-jlcr899>3.0.co;2-0

文献信息

• Synthesis and Anti-dengue Virus Activity of 5-Ethynylimidazole-4-carboxamide (EICA) Nucleotide Prodrugs
  作者：Motoki Nakamura、Kentaro Uemura、Noriko Saito-Tarashima、Akihiko Sato、Yasuko Orba、Hirofumi Sawa、Akira Matsuda、Katsumi Maenaka、Noriaki Minakawa

  DOI：10.1248/cpb.c21-01038

  日期：2022.3.1

  We previously showed that 5-ethynyl-(1-β-D-ribofuranosyl)imidazole-4-carboxamide (1; EICAR) is a potent anti-dengue virus (DENV) compound but is cytotoxic to some cell lines, while its 4-thio derivative, 5-ethynyl-(4-thio-1-β-D-ribofuranosyl)imidazole-4-carboxamide (2; 4′-thioEICAR), has less cytotoxicity but also less anti-DENV activity. Based on the hypothesis that the lower anti-DENV activity of 2 is due to reduced susceptibility to phosphorylation by cellular kinase(s), we investigated whether a monophosphate prodrug of 2 can improve its activity. Here, we first prepared two types of prodrug of 1, which revealed that the S-acyl-2-thioethyl (SATE) prodrug had stronger anti-DENV activity than the aryloxyphosphoramidate (so-called ProTide) prodrug. Based on these findings, we next prepared the SATE prodrug of 4′-thioEICAR 18. As expected, the resulting 18 showed potent anti-DENV activity, which was comparable to that of 1; however, its cytotoxicity was also increased relative to 2. Our findings suggest that prodrugs of 4′-thioribonucleoside derivatives such as EICAR (1) represent an effective approach to developing potent biologically active compounds; however, the balance between antiviral activity and cytotoxicity remains to be addressed.

  我们之前表明，5-乙炔基-(1-β-D-呋喃核糖基)咪唑-4-甲酰胺 (1; EICAR) 是一种有效的抗登革热病毒 (DENV) 化合物，但对某些细胞系具有细胞毒性，而其 4-硫代衍生物 5-乙炔基-(4-硫代-1-β-D-呋喃核糖基)咪唑-4-甲酰胺 (2; 4'-thioEICAR) 具有较低的细胞毒性，但抗 DENV 活性也较低。基于2的较低抗DENV活性是由于对细胞激酶磷酸化的敏感性降低所致的假设，我们研究了2的单磷酸前药是否可以提高其活性。在这里，我们首先制备了两种1的前药，结果表明S-酰基-2-硫乙基（SATE）前药比芳氧基氨基磷酸酯（所谓的ProTide）前药具有更强的抗DENV活性。基于这些发现，我们接下来制备了4'-thioEICAR 18的SATE前药。正如预期的那样，所得的18显示出有效的抗DENV活性，与1相当；然而，其细胞毒性相对于 2 也有所增加。我们的研究结果表明 EICAR (1) 等 4'-硫核糖核苷衍生物的前药代表了开发有效生物活性化合物的有效方法；然而，抗病毒活性和细胞毒性之间的平衡仍有待解决。
• 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。