cis-2-(5-methyl-5-carboxymethyl-1,3-dioxan-2-yl)-4-(4-fluorophenyl)-5-(2-methylsulfonylpyrimidin-4-yl)-1H-imidazole | 218162-34-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: cis-2-(5-methyl-5-carboxymethyl-1,3-dioxan-2-yl)-4-(4-fluorophenyl)-5-(2-methylsulfonylpyrimidin-4-yl)-1H-imidazole
• CAS: 218162-34-6
• 化学式: C₂₁H₂₁FN₄O₆S
• 分子量: 476.485
• InChiKey: LANNGKCGQHXHKS-RVWIWJKTSA-N

物化性质

• 沸点：
  701.983±70.00 °C(Press: 760.00 Torr)(predicted)
• 密度：
  1.388±0.06 g/cm3(Temp: 25 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  33.0
• 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：
  133.36
• 氢给体数：
  1.0
• 氢受体数：
  9.0

反应信息

• 作为产物：
  描述：

  4-甲基-2-甲硫基嘧啶 在 ammonium acetate 、 sodium hexamethyldisilazane 、 对甲苯磺酸 、 二甲基亚砜 、 间氯过氧苯甲酸 、 原甲酸三甲酯 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 30.5h， 生成 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