4-bromo-7-(cyclopropylmethoxy)-6-methoxycinnoline | 1407978-34-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: 4-bromo-7-(cyclopropylmethoxy)-6-methoxycinnoline
• 英文别名: 4-Bromo-7-(cyclopropylmethoxy)-6-methoxycinnoline
• CAS: 1407978-34-0
• 化学式: C₁₃H₁₃BrN₂O₂
• 分子量: 309.162
• InChiKey: SKSJLMFQEZUDMC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  44.2
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  4-bromo-7-fluoro-6-methoxycinnoline 、 羟甲基环丙烷 在 lithium hexamethyldisilazane 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以83%的产率得到4-bromo-7-(cyclopropylmethoxy)-6-methoxycinnoline
  参考文献：
  名称：

  Use of structure based design to increase selectivity of pyridyl-cinnoline phosphodiesterase 10A (PDE10A) inhibitors against phosphodiesterase 3 (PDE3)

  摘要：

  We report our successful effort to increase the PDE3 selectivity of PDE10A inhibitor pyridyl cinnoline 1 using a combination of computational modeling and structural-activity relationship investigations. An analysis of the PDE3 catalytic domain compared to the co-crystal structure of cinnoline analog 1 in PDE10A revealed two areas of structural differences in the active sites and suggested areas on the scaffold that could be modified to exploit those unique structural features. Once SAR established the cinnoline as the optimal scaffold, modifications on the methoxy groups of the cinnoline and the methyl group on the pyridine led to the discovery of compounds 33 and 36. Both compounds achieved significant improvement in selectivity against PDE3 while maintaining their PDE10A inhibitory activity and in vivo metabolic stability comparable to 1. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.09.010

文献信息

• Use of structure based design to increase selectivity of pyridyl-cinnoline phosphodiesterase 10A (PDE10A) inhibitors against phosphodiesterase 3 (PDE3)
  作者：Essa Hu、Roxanne K. Kunz、Shannon Rumfelt、Kristin L. Andrews、Chun Li、Stephen A. Hitchcock、Michelle Lindstrom、James Treanor

  DOI：10.1016/j.bmcl.2012.09.010

  日期：2012.11

  We report our successful effort to increase the PDE3 selectivity of PDE10A inhibitor pyridyl cinnoline 1 using a combination of computational modeling and structural-activity relationship investigations. An analysis of the PDE3 catalytic domain compared to the co-crystal structure of cinnoline analog 1 in PDE10A revealed two areas of structural differences in the active sites and suggested areas on the scaffold that could be modified to exploit those unique structural features. Once SAR established the cinnoline as the optimal scaffold, modifications on the methoxy groups of the cinnoline and the methyl group on the pyridine led to the discovery of compounds 33 and 36. Both compounds achieved significant improvement in selectivity against PDE3 while maintaining their PDE10A inhibitory activity and in vivo metabolic stability comparable to 1. (C) 2012 Elsevier Ltd. All rights reserved.