5-(sec-butyl)-6-(2-chloro-6-fluorobenzyl)-2-thioxo-2,3-dihydropyrimidin-4(1H)-one | 1044749-17-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 5-(sec-butyl)-6-(2-chloro-6-fluorobenzyl)-2-thioxo-2,3-dihydropyrimidin-4(1H)-one
• CAS: 1044749-17-8
• 化学式: C₁₅H₁₆ClFN₂OS
• 分子量: 326.822
• InChiKey: IGORFCMDOMDYMK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.33
• 重原子数：
  21.0
• 可旋转键数：
  4.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  48.65
• 氢给体数：
  2.0
• 氢受体数：
  2.0

反应信息

• 作为反应物：
  描述：

  5-(sec-butyl)-6-(2-chloro-6-fluorobenzyl)-2-thioxo-2,3-dihydropyrimidin-4(1H)-one 、 alpha-溴-4-甲氧基苯乙酮 在 sodium methylate 作用下， 以 甲醇 为溶剂， 以83%的产率得到4-[(2-chloro-6-fluoro-phenyl)methyl]-2-[2-(4-methoxyphenyl)-2-oxo-ethyl]sulfanyl-5-sec-butyl-1H-pyrimidin-6-one
  参考文献：
  名称：

  5-Alkyl-6-benzyl-2-(2-oxo-2-phenylethylsulfanyl)pyrimidin-4(3H)-ones, a Series of Anti-HIV-1 Agents of the Dihydro-alkoxy-benzyl-oxopyrimidine Family with Peculiar Structure−Activity Relationship Profile

  摘要：

  A series of dihydro-alkylthio-benzyl-oxopyrimidines (S-DABOs) bearing a 2-aryl-2-oxoethylsulfanyl chain at pyrimidine C2, an alkyl group at C5, and a 2,6-dichloro-, 2-chloro-6-fluoro-, and 2,6-difluoro-benzyl substitution at C6 (oxophenethyl-S-DABOs, 6-8) is here described. The new compounds showed low micromolar to low nanomolar (in one case subnanomolar) inhibitory activity against wt HIV-1. Against clinically relevant HIV-1 mutants (K103N, Y181C, and Y188L) as well as in enzyme (wt and K103N, Y181I, and L1001 mutated RTs) assays, compounds carrying an ethylliso-propyl group at C5 and a 2,6-dichloro-/2-chloro-6-fluoro-benzyl moiety at C6 were the most potent derivatives, also characterized by low fold resistance ratio. Interestingly, the structure-activity relationship (SAR) data drawn from this DABO series are more related to HEPT than to DABO derivatives. These findings were at least in part rationalized by the description of a fair superimposition between the 6-8 and TNK-651 (a HEPT analogue) binding modes in both WT and Y181C RTs.

  DOI：

  10.1021/jm800340w
• 作为产物：
  描述：

  、 硫脲 在 potassium ethoxide 作用下， 以 乙醇 为溶剂， 反应 90.0h， 以21%的产率得到5-(sec-butyl)-6-(2-chloro-6-fluorobenzyl)-2-thioxo-2,3-dihydropyrimidin-4(1H)-one
  参考文献：
  名称：

  5-Alkyl-6-benzyl-2-(2-oxo-2-phenylethylsulfanyl)pyrimidin-4(3H)-ones, a Series of Anti-HIV-1 Agents of the Dihydro-alkoxy-benzyl-oxopyrimidine Family with Peculiar Structure−Activity Relationship Profile

  摘要：

  A series of dihydro-alkylthio-benzyl-oxopyrimidines (S-DABOs) bearing a 2-aryl-2-oxoethylsulfanyl chain at pyrimidine C2, an alkyl group at C5, and a 2,6-dichloro-, 2-chloro-6-fluoro-, and 2,6-difluoro-benzyl substitution at C6 (oxophenethyl-S-DABOs, 6-8) is here described. The new compounds showed low micromolar to low nanomolar (in one case subnanomolar) inhibitory activity against wt HIV-1. Against clinically relevant HIV-1 mutants (K103N, Y181C, and Y188L) as well as in enzyme (wt and K103N, Y181I, and L1001 mutated RTs) assays, compounds carrying an ethylliso-propyl group at C5 and a 2,6-dichloro-/2-chloro-6-fluoro-benzyl moiety at C6 were the most potent derivatives, also characterized by low fold resistance ratio. Interestingly, the structure-activity relationship (SAR) data drawn from this DABO series are more related to HEPT than to DABO derivatives. These findings were at least in part rationalized by the description of a fair superimposition between the 6-8 and TNK-651 (a HEPT analogue) binding modes in both WT and Y181C RTs.

  DOI：

  10.1021/jm800340w