2-carboxaldehyde-4-(4-fluorophenyl)-5-(2-methylsulfanylpyrimidin-4-yl)-1H-imidazole

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 2-carboxaldehyde-4-(4-fluorophenyl)-5-(2-methylsulfanylpyrimidin-4-yl)-1H-imidazole
• 英文别名: 4-(4-fluorophenyl)-5-(2-methylsulfanylpyrimidin-4-yl)-1H-imidazole-2-carbaldehyde
• 化学式: C₁₅H₁₁FN₄OS
• 分子量: 314.343
• InChiKey: DYZATLBLLZJIHM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  96.8
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2-carboxaldehyde-4-(4-fluorophenyl)-5-(2-methylsulfanylpyrimidin-4-yl)-1H-imidazole 在 对甲苯磺酸 、 间氯过氧苯甲酸 作用下， 以 N-甲基吡咯烷酮 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成
  参考文献：
  名称：

  RPR203494 a pyrimidine analogue of the p38 inhibitor RPR200765A with an improved in vitro potency

  摘要：

  Following the discovery of RPR200765, a series of pyrimidine analogues have been prepared as backups. Amongst them, RPR203494 was identified with a better in vitro profile than RPR200765A. (C) 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(01)00034-8
• 作为产物：
  描述：

  4-甲基-2-甲硫基嘧啶 在 ammonium acetate 、 氢溴酸 、 sodium hexamethyldisilazane 、 溶剂黄146 、 二甲基亚砜 作用下， 以 四氢呋喃 为溶剂， 生成 2-carboxaldehyde-4-(4-fluorophenyl)-5-(2-methylsulfanylpyrimidin-4-yl)-1H-imidazole
  参考文献：
  名称：

  RPR203494 a pyrimidine analogue of the p38 inhibitor RPR200765A with an improved in vitro potency

  摘要：

  Following the discovery of RPR200765, a series of pyrimidine analogues have been prepared as backups. Amongst them, RPR203494 was identified with a better in vitro profile than RPR200765A. (C) 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(01)00034-8

文献信息

• An Algorithm-Directed Two-Component Library Synthesized Via Solid-Phase Methodology Yielding Potent and Orally Bioavailable p38 MAP Kinase Inhibitors
  作者：Jeffrey M. McKenna、Frank Halley、John E. Souness、Iain M. McLay、Stephen D. Pickett、Alan J. Collis、Kenneth Page、Imtiaz Ahmed

  DOI：10.1021/jm011132l

  日期：2002.5.1

  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.