3-methyl-5-(methylthio)-6-(2,3,5-tri-O-benzoyl-β-D-ribofuranosyl)imidazo[4,5-d]isothiazole | 186099-61-6

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 3-methyl-5-(methylthio)-6-(2,3,5-tri-O-benzoyl-β-D-ribofuranosyl)imidazo[4,5-d]isothiazole
• 英文别名: [(2R,3R,4R,5R)-3,4-dibenzoyloxy-5-(3-methyl-5-methylsulfanylimidazo[4,5-d][1,2]thiazol-6-yl)oxolan-2-yl]methyl benzoate
• CAS: 186099-61-6
• 化学式: C₃₂H₂₇N₃O₇S₂
• 分子量: 629.714
• InChiKey: IYCAZFKVDOOYSK-MIRJVGOZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.6
• 重原子数：
  44
• 可旋转键数：
  12
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  172
• 氢给体数：
  0
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  3-methyl-5-(methylthio)-6-(2,3,5-tri-O-benzoyl-β-D-ribofuranosyl)imidazo[4,5-d]isothiazole 在 氨 作用下， 以 甲醇 为溶剂， 反应 24.0h， 以61%的产率得到(2R,3S,4R,5R)-2-(hydroxymethyl)-5-(3-methyl-5-methylsulfanyl-imidazo[4,5-d]isothiazol-6-yl)tetrahydrofuran-3,4-diol
  参考文献：
  名称：

  Synthesis, Antiproliferative and Antiviral Activity of Imidazo[4,5-d]isothiazole Nucleosides as 5:5 Fused Analogs of Nebularine and 6-Methylpurine Ribonucleoside

  摘要：

  A series of imidazo[4,5-d]isothiazole nucleosides related to the antibiotic nebularine and the highly cytotoxic 6-methyl-9-beta-D-ribofuranosylpurine have been synthesized from the corresponding heterocycles. The sodium salt glycosylation of the imidazo[4,5-d]isothiazoles proceeded smoothly, giving mixtures of N-4 and N-6 regioisomers in generally good yields. The protected derivatives were deblocked using standard conditions to afford the desired imidazo[4,5-d]isothiazole nucleosides, usually as crystalline solids. None of the new nucleosides or heterocycles displayed selective activity against human cytomegalovirus (HCMV) or herpes simplex virus type 1 (HSV-1). The N-6 glycosylated imidazo[4,5-d]isothiazoles were completely inactive up to the highest concentration tested. The N-6 glycosylated imidazo[4,5-d]isothiazoles also were inactive in antiproliferative and cytotoxicity assays, except for 3-methyl-6-beta-D-ribofuranosylimidazo[4,5-d]isothiazole (15a) and 5-(benzylthio)-6-(2-deoxy-beta-D-ribofuranosyl)imidazo[4,5-d]isothiazole (5e), which showed moderate inhibition of L1210 cell growth. However, the heterocycles and several of the N-4 glycosylated derivatives were toxic to HFF, KB and L1210 cells; compounds with 5-benzylthio substituents were the most cytotoxic agents in this series.

  DOI：

  10.1021/jm960605z
• 作为产物：
  描述：

  4-(2-deoxy-3,5-di-O-p-toluoyl-β-D-erythro-pentofuranosyl)-3-methylimidazo[4,5-d]isothiazole 在 N,O-双三甲硅基乙酰胺 、 三氟甲磺酸三甲基硅酯 、 sodium methylate 作用下， 以 甲醇 为溶剂， 反应 18.0h， 生成 3-methyl-5-(methylthio)-6-(2,3,5-tri-O-benzoyl-β-D-ribofuranosyl)imidazo[4,5-d]isothiazole
  参考文献：
  名称：

  Synthesis, Antiproliferative and Antiviral Activity of Imidazo[4,5-d]isothiazole Nucleosides as 5:5 Fused Analogs of Nebularine and 6-Methylpurine Ribonucleoside

  摘要：

  A series of imidazo[4,5-d]isothiazole nucleosides related to the antibiotic nebularine and the highly cytotoxic 6-methyl-9-beta-D-ribofuranosylpurine have been synthesized from the corresponding heterocycles. The sodium salt glycosylation of the imidazo[4,5-d]isothiazoles proceeded smoothly, giving mixtures of N-4 and N-6 regioisomers in generally good yields. The protected derivatives were deblocked using standard conditions to afford the desired imidazo[4,5-d]isothiazole nucleosides, usually as crystalline solids. None of the new nucleosides or heterocycles displayed selective activity against human cytomegalovirus (HCMV) or herpes simplex virus type 1 (HSV-1). The N-6 glycosylated imidazo[4,5-d]isothiazoles were completely inactive up to the highest concentration tested. The N-6 glycosylated imidazo[4,5-d]isothiazoles also were inactive in antiproliferative and cytotoxicity assays, except for 3-methyl-6-beta-D-ribofuranosylimidazo[4,5-d]isothiazole (15a) and 5-(benzylthio)-6-(2-deoxy-beta-D-ribofuranosyl)imidazo[4,5-d]isothiazole (5e), which showed moderate inhibition of L1210 cell growth. However, the heterocycles and several of the N-4 glycosylated derivatives were toxic to HFF, KB and L1210 cells; compounds with 5-benzylthio substituents were the most cytotoxic agents in this series.

  DOI：

  10.1021/jm960605z

文献信息

• Synthesis, Antiproliferative and Antiviral Activity of Imidazo[4,5-<i>d</i>]isothiazole Nucleosides as 5:5 Fused Analogs of Nebularine and 6-Methylpurine Ribonucleoside
  作者：Eric E. Swayze、John C. Drach、Linda L. Wotring、Leroy B. Townsend

  DOI：10.1021/jm960605z

  日期：1997.2.1

  A series of imidazo[4,5-d]isothiazole nucleosides related to the antibiotic nebularine and the highly cytotoxic 6-methyl-9-beta-D-ribofuranosylpurine have been synthesized from the corresponding heterocycles. The sodium salt glycosylation of the imidazo[4,5-d]isothiazoles proceeded smoothly, giving mixtures of N-4 and N-6 regioisomers in generally good yields. The protected derivatives were deblocked using standard conditions to afford the desired imidazo[4,5-d]isothiazole nucleosides, usually as crystalline solids. None of the new nucleosides or heterocycles displayed selective activity against human cytomegalovirus (HCMV) or herpes simplex virus type 1 (HSV-1). The N-6 glycosylated imidazo[4,5-d]isothiazoles were completely inactive up to the highest concentration tested. The N-6 glycosylated imidazo[4,5-d]isothiazoles also were inactive in antiproliferative and cytotoxicity assays, except for 3-methyl-6-beta-D-ribofuranosylimidazo[4,5-d]isothiazole (15a) and 5-(benzylthio)-6-(2-deoxy-beta-D-ribofuranosyl)imidazo[4,5-d]isothiazole (5e), which showed moderate inhibition of L1210 cell growth. However, the heterocycles and several of the N-4 glycosylated derivatives were toxic to HFF, KB and L1210 cells; compounds with 5-benzylthio substituents were the most cytotoxic agents in this series.