cis-2-(5-methyl-5-carboxymethyl-1,3-dioxan-2-yl)-4-(4-fluorophenyl)-5-(2-methylsulfanylpyrimidin-4-yl)-1H-imidazole | 218161-96-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并嘧啶类
• 英文名称: cis-2-(5-methyl-5-carboxymethyl-1,3-dioxan-2-yl)-4-(4-fluorophenyl)-5-(2-methylsulfanylpyrimidin-4-yl)-1H-imidazole
• CAS: 218161-96-7
• 化学式: C₂₁H₂₁FN₄O₄S
• 分子量: 444.487
• InChiKey: UGFQSBITLNTPAH-RVWIWJKTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.62
• 重原子数：
  31.0
• 可旋转键数：
  5.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  99.22
• 氢给体数：
  1.0
• 氢受体数：
  8.0

反应信息

• 作为反应物：
  描述：

  cis-2-(5-methyl-5-carboxymethyl-1,3-dioxan-2-yl)-4-(4-fluorophenyl)-5-(2-methylsulfanylpyrimidin-4-yl)-1H-imidazole 在 间氯过氧苯甲酸 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 16.0h， 以82%的产率得到cis-2-(5-methyl-5-carboxymethyl-1,3-dioxan-2-yl)-4-(4-fluorophenyl)-5-(2-methylsulfonylpyrimidin-4-yl)-1H-imidazole
  参考文献：
  名称：

  An Algorithm-Directed Two-Component Library Synthesized Via Solid-Phase Methodology Yielding Potent and Orally Bioavailable p38 MAP Kinase Inhibitors

  摘要：

  Previously we reported the identification of RPR200765A, a potent orally bioavailable pyridine-imidazole inhibitor of p38 mitogen-activated protein (MAP) kinase which suppressed paw swelling and joint pathology in streptococcal cell wall-induced arthritis. Herein, we report the use of solid-phase combinatorial organic synthesis for the parallel processing of a related pyrimidine-imidazole-based library with two points of structural variability. We report also that the application of a computer algorithm, the Monte Carlo Monomer Selection, maximized both the combinatorial synthetic efficiency and the bioavailability of the final compounds. In conjunction with the synthetic protocols, the polymer-supported quench technique was applied to the purification of the final compounds. Through rapid evaluation of the library using a p38 kinase assay and permeability assays, it was possible to identify a number of potent and orally bioavailable p38 MAP kinase inhibitors suitable for further biological investigation.

  DOI：

  10.1021/jm011132l
• 作为产物：
  描述：

  1-(4-fluorophenyl)-2-(2-(methylthio)pyrimidin-4-yl)ethanone 在 ammonium acetate 、 对甲苯磺酸 、 二甲基亚砜 、 原甲酸三甲酯 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 11.0h， 生成 cis-2-(5-methyl-5-carboxymethyl-1,3-dioxan-2-yl)-4-(4-fluorophenyl)-5-(2-methylsulfanylpyrimidin-4-yl)-1H-imidazole
  参考文献：
  名称：

  An Algorithm-Directed Two-Component Library Synthesized Via Solid-Phase Methodology Yielding Potent and Orally Bioavailable p38 MAP Kinase Inhibitors

  摘要：

  Previously we reported the identification of RPR200765A, a potent orally bioavailable pyridine-imidazole inhibitor of p38 mitogen-activated protein (MAP) kinase which suppressed paw swelling and joint pathology in streptococcal cell wall-induced arthritis. Herein, we report the use of solid-phase combinatorial organic synthesis for the parallel processing of a related pyrimidine-imidazole-based library with two points of structural variability. We report also that the application of a computer algorithm, the Monte Carlo Monomer Selection, maximized both the combinatorial synthetic efficiency and the bioavailability of the final compounds. In conjunction with the synthetic protocols, the polymer-supported quench technique was applied to the purification of the final compounds. Through rapid evaluation of the library using a p38 kinase assay and permeability assays, it was possible to identify a number of potent and orally bioavailable p38 MAP kinase inhibitors suitable for further biological investigation.

  DOI：

  10.1021/jm011132l