7-[2-(5-methyl-1-phenyl-1H-benzimidazol-2-yl)ethyl]imidazo[1,5-b]pyridazine | 1613149-05-5

• 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: 7-[2-(5-methyl-1-phenyl-1H-benzimidazol-2-yl)ethyl]imidazo[1,5-b]pyridazine
• 英文别名: 7-[2-(5-Methyl-1-Phenyl-1h-Benzimidazol-2-Yl)ethyl]imidazo[1,5-B]pyridazine；7-[2-(5-methyl-1-phenylbenzimidazol-2-yl)ethyl]imidazo[1,5-b]pyridazine
• CAS: 1613149-05-5
• 化学式: C₂₂H₁₉N₅
• 分子量: 353.426
• InChiKey: UVMQXAHTUGJOHF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  27
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  48
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  7-[2-(5-methyl-1-phenyl-1H-benzimidazol-2-yl)ethyl]imidazo[1,5-b]pyridazine 在 N-溴代丁二酰亚胺(NBS) 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 反应 1.0h， 以81%的产率得到5-bromo-7-[2-(5-methyl-1-phenyl-1H-benzimidazol-2-yl)ethyl]imidazo[1,5-b]pyridazine
  参考文献：
  名称：

  Novel benzimidazole derivatives as phosphodiesterase 10A (PDE10A) inhibitors with improved metabolic stability

  摘要：

  In this study, we report the identification of potent benzimidazoles as PDE10A inhibitors. We first identified imidazopyridine 1 as a high-throughput screening hit compound from an in-house library. Next, optimization of the imidazopyridine moiety to improve inhibitory activity gave imidazopyridinone 10b. Following further structure-activity relationship development by reducing lipophilicity and introducing substituents, we acquired 35, which exhibited both improved metabolic stability and reduced CYP3A4 time-dependent inhibition. (C) 2014 Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmc.2014.04.023
• 作为产物：
  描述：

  methyl 3-(5-methyl-1-phenyl-1H-benzimidazol-2-yl)propanoate 在 水 、 1-丙基磷酸酐 、 sodium hydroxide 作用下， 以 乙酸乙酯 为溶剂， 反应 32.0h， 生成 7-[2-(5-methyl-1-phenyl-1H-benzimidazol-2-yl)ethyl]imidazo[1,5-b]pyridazine
  参考文献：
  名称：

  Novel benzimidazole derivatives as phosphodiesterase 10A (PDE10A) inhibitors with improved metabolic stability

  摘要：

  In this study, we report the identification of potent benzimidazoles as PDE10A inhibitors. We first identified imidazopyridine 1 as a high-throughput screening hit compound from an in-house library. Next, optimization of the imidazopyridine moiety to improve inhibitory activity gave imidazopyridinone 10b. Following further structure-activity relationship development by reducing lipophilicity and introducing substituents, we acquired 35, which exhibited both improved metabolic stability and reduced CYP3A4 time-dependent inhibition. (C) 2014 Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmc.2014.04.023

文献信息

• Novel benzimidazole derivatives as phosphodiesterase 10A (PDE10A) inhibitors with improved metabolic stability
  作者：Ayaka Chino、Naoyuki Masuda、Yasushi Amano、Kazuya Honbou、Takuma Mihara、Mayako Yamazaki、Masaki Tomishima

  DOI：10.1016/j.bmc.2014.04.023

  日期：2014.7

  In this study, we report the identification of potent benzimidazoles as PDE10A inhibitors. We first identified imidazopyridine 1 as a high-throughput screening hit compound from an in-house library. Next, optimization of the imidazopyridine moiety to improve inhibitory activity gave imidazopyridinone 10b. Following further structure-activity relationship development by reducing lipophilicity and introducing substituents, we acquired 35, which exhibited both improved metabolic stability and reduced CYP3A4 time-dependent inhibition. (C) 2014 Published by Elsevier Ltd.