1-isopropyl-3-methyl-2-oxo-2,3-dihydro-1H-benzoimidazole-5-carbaldehyde | 865443-86-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并咪唑类
• 英文名称: 1-isopropyl-3-methyl-2-oxo-2,3-dihydro-1H-benzoimidazole-5-carbaldehyde
• 英文别名: 3-Methyl-2-oxo-1-propan-2-ylbenzimidazole-5-carbaldehyde
• CAS: 865443-86-3
• 化学式: C₁₂H₁₄N₂O₂
• 分子量: 218.255
• InChiKey: LKHNZCTUYBKGAX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  40.6
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1-isopropyl-3-methyl-2-oxo-2,3-dihydro-1H-benzoimidazole-5-carbaldehyde 、 Α-(对甲苯磺酰基)-4-氟苄基异腈 在 potassium carbonate 作用下， 以 乙腈 为溶剂， 反应 36.0h， 以11%的产率得到5-[4-(4-Fluoro-phenyl)-oxazol-5-yl]-1-isopropyl-3-methyl-1,3-dihydrobenzoimidazol-2-one
  参考文献：
  名称：

  Theoretical and Experimental Design of Atypical Kinase Inhibitors:  Application to p38 MAP Kinase

  摘要：

  Mimics of the benzimidazolone nucleus found in inhibitors of p38 kinase are proposed, and their theoretical potential as bioisosteres is described. A set of calculated descriptors relevant to the anticipated binding interaction for the fragments 1-methyl-1H-benzotriazole 5, 3-methyl-benzo[d]isoxazole 3, and 3-methyl-[1,2,4]triazolo[4,3-a]pyridine 4, pyridine 1, and 1,3-dimethyl-1,3-dihydro-benzoimidazol-2-one 2 are reported. The design considerations and synthesis of p38 inhibitors based on these H-bond acceptor fragments is detailed. Comparative evaluation of the pyridine-, benzimidazolone-, benzotriazole-, and triazolopyridine-based inhibitors shows the triazoles 20 and 25 to be significantly more potent experimentally than the benzimidazolone after which they were modeled. An X-ray crystal structure of 25 bound to the active site shows that the triazole group serves as the H-bond acceptor but unexpectedly as a dual acceptor, inducing movement of the crossover connection of p38alpha. The computed descriptors for the hydrophobic and pi-pi interaction capacities were the most useful in ranking potency.

  DOI：

  10.1021/jm050346q
• 作为产物：
  描述：

  4-异丙基氨基-3-硝基苯甲酸甲酯 在 palladium on activated charcoal 、 四丁基氯化铵 、 碳酸氢钠 2,2,6,6-tetramethyl-piperidine-N-oxyl 、 N-氯代丁二酰亚胺 、 锂硼氢 、 氢气 、 sodium hydride 、 sodium carbonate 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 二氯甲烷 、 二甲基亚砜 、 甲苯 为溶剂， 22.0~80.0 ℃ 、275.79 kPa 条件下， 反应 118.0h， 生成 1-isopropyl-3-methyl-2-oxo-2,3-dihydro-1H-benzoimidazole-5-carbaldehyde
  参考文献：
  名称：

  Theoretical and Experimental Design of Atypical Kinase Inhibitors:  Application to p38 MAP Kinase

  摘要：

  Mimics of the benzimidazolone nucleus found in inhibitors of p38 kinase are proposed, and their theoretical potential as bioisosteres is described. A set of calculated descriptors relevant to the anticipated binding interaction for the fragments 1-methyl-1H-benzotriazole 5, 3-methyl-benzo[d]isoxazole 3, and 3-methyl-[1,2,4]triazolo[4,3-a]pyridine 4, pyridine 1, and 1,3-dimethyl-1,3-dihydro-benzoimidazol-2-one 2 are reported. The design considerations and synthesis of p38 inhibitors based on these H-bond acceptor fragments is detailed. Comparative evaluation of the pyridine-, benzimidazolone-, benzotriazole-, and triazolopyridine-based inhibitors shows the triazoles 20 and 25 to be significantly more potent experimentally than the benzimidazolone after which they were modeled. An X-ray crystal structure of 25 bound to the active site shows that the triazole group serves as the H-bond acceptor but unexpectedly as a dual acceptor, inducing movement of the crossover connection of p38alpha. The computed descriptors for the hydrophobic and pi-pi interaction capacities were the most useful in ranking potency.

  DOI：

  10.1021/jm050346q