[(3aS,4R,6R,6aR)-2,2-dimethyl-4-[[6-methyl-2-methylsulfanyl-5-(2-trimethylsilylethynyl)pyrimidin-4-yl]amino]-4,5,6,6a-tetrahydro-3aH-cyclopenta[d][1,3]dioxol-6-yl]methanol | 1208990-14-0

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫醚类
• 英文名称: [(3aS,4R,6R,6aR)-2,2-dimethyl-4-[[6-methyl-2-methylsulfanyl-5-(2-trimethylsilylethynyl)pyrimidin-4-yl]amino]-4,5,6,6a-tetrahydro-3aH-cyclopenta[d][1,3]dioxol-6-yl]methanol
• CAS: 1208990-14-0
• 化学式: C₂₀H₃₁N₃O₃SSi
• 分子量: 421.636
• InChiKey: JOLGVLRJNSOUFG-DZUCGIPZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.05
• 重原子数：
  28
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.7
• 拓扑面积：
  102
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  [(3aS,4R,6R,6aR)-2,2-dimethyl-4-[[6-methyl-2-methylsulfanyl-5-(2-trimethylsilylethynyl)pyrimidin-4-yl]amino]-4,5,6,6a-tetrahydro-3aH-cyclopenta[d][1,3]dioxol-6-yl]methanol 在 盐酸 、 bis-triphenylphosphine-palladium(II) chloride 、 copper(l) iodide 、 四乙基氟化铵水合物 、 三乙胺 、 间氯过氧苯甲酸 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 水 、 乙腈 为溶剂， 生成 (1R,2S,3R,5R)-3-[[2-(2,2-dimethylpropylamino)-5-(5-ethylfuro[2,3-c]pyridin-2-yl)-6-methyl-pyrimidin-4-yl]amino]-5-(hydroxymethyl)cyclopentane-1,2-diol
  参考文献：
  名称：

  Pyridofuran substituted pyrimidine derivatives as HCV replication (replicase) inhibitors

  摘要：

  Introduction of nitrogen atom into the benzene ring of a previously identified HCV replication (replicase) benzofuran inhibitor 2, resulted in the discovery of the more potent pyridofuran analogue 5. Subsequent introduction of small alkyl and alkoxy ligands into the pyridine ring resulted in further improvements in replicon potency. Replacement of the 4-chloro moiety on the pyrimidine core with a methyl group, and concomitant monoalkylation of the C-2 amino moiety resulted in the identification of several inhibitors with desirable characteristics. Inhibitor 41, from the monosubstituted pyridofuran and inhibitor 50 from the disubstituted series displayed excellent potency, selectivity (GAPDH/MTS CC50) and PK parameters in all species studied, while the selectivity in the thymidine incorporation assay (DNA.CC50) was low. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.06.021
• 作为产物：
  描述：

  4-氯-5-碘-6-甲基-2-(甲硫基)嘧啶 在 bis-triphenylphosphine-palladium(II) chloride 、 copper(l) iodide 、 甲烷磺酸 、 三乙胺 作用下， 以 1,4-二氧六环 、 乙醇 为溶剂， 生成 [(3aS,4R,6R,6aR)-2,2-dimethyl-4-[[6-methyl-2-methylsulfanyl-5-(2-trimethylsilylethynyl)pyrimidin-4-yl]amino]-4,5,6,6a-tetrahydro-3aH-cyclopenta[d][1,3]dioxol-6-yl]methanol
  参考文献：
  名称：

  Pyridofuran substituted pyrimidine derivatives as HCV replication (replicase) inhibitors

  摘要：

  Introduction of nitrogen atom into the benzene ring of a previously identified HCV replication (replicase) benzofuran inhibitor 2, resulted in the discovery of the more potent pyridofuran analogue 5. Subsequent introduction of small alkyl and alkoxy ligands into the pyridine ring resulted in further improvements in replicon potency. Replacement of the 4-chloro moiety on the pyrimidine core with a methyl group, and concomitant monoalkylation of the C-2 amino moiety resulted in the identification of several inhibitors with desirable characteristics. Inhibitor 41, from the monosubstituted pyridofuran and inhibitor 50 from the disubstituted series displayed excellent potency, selectivity (GAPDH/MTS CC50) and PK parameters in all species studied, while the selectivity in the thymidine incorporation assay (DNA.CC50) was low. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.06.021