3-bromo-1H-pyrazolo[3,4-c]pyridazine | 1260741-42-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡唑并吡啶类
• 英文名称: 3-bromo-1H-pyrazolo[3,4-c]pyridazine
• 英文别名: 3-Bromo-1H-pyrazolo[3,4-c]pyridazine
• CAS: 1260741-42-1
• 化学式: C₅H₃BrN₄
• 分子量: 199.01
• InChiKey: PSXNIVSJYFFTCC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  10
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  54.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-bromo-1H-pyrazolo[3,4-c]pyridazine 在 palladium 10% on activated carbon 、 氢气 、 sodium methylate 、 caesium carbonate 、 三乙胺 作用下， 以 甲醇 、 二甲基亚砜 、 N,N-二甲基甲酰胺 为溶剂， 20.0~150.0 ℃ 、100.0 kPa 条件下， 反应 11.0h， 生成 (2-(1-(2-fluorobenzyl)-1H-pyrazolo[3,4-c]pyridazin-3-yl)pyrimidine-4,5,6-triamine)
  参考文献：
  名称：

  Discovery of the Soluble Guanylate Cyclase Stimulator Vericiguat (BAY 1021189) for the Treatment of Chronic Heart Failure

  摘要：

  The first-in-class soluble guanylate cyclase (sGC) stimulator riociguat was recently introduced as a novel treatment option for pulmonary hypertension. Despite its outstanding pharmacological profile, application of riociguat in other cardiovascular indications is limited by its short half-life, necessitating a three times daily dosing regimen. In our efforts to further optimize the compound class, we have uncovered interesting structure activity relationships and were able to decrease oxidative metabolism significantly. These studies resulting in the discovery of once daily sGC stimulator vericiguat (compound 24, BAY 1021189), currently in phase 3 trials for chronic heart failure, are now reported.

  DOI：

  10.1021/acs.jmedchem.7b00449
• 作为产物：
  描述：

  1H-吡唑并[3,4-c]吡嗪-3(2H)-酮 在 三溴氧磷 作用下， 以 环丁砜 为溶剂， 反应 3.0h， 以62%的产率得到3-bromo-1H-pyrazolo[3,4-c]pyridazine
  参考文献：
  名称：

  Discovery of the Soluble Guanylate Cyclase Stimulator Vericiguat (BAY 1021189) for the Treatment of Chronic Heart Failure

  摘要：

  The first-in-class soluble guanylate cyclase (sGC) stimulator riociguat was recently introduced as a novel treatment option for pulmonary hypertension. Despite its outstanding pharmacological profile, application of riociguat in other cardiovascular indications is limited by its short half-life, necessitating a three times daily dosing regimen. In our efforts to further optimize the compound class, we have uncovered interesting structure activity relationships and were able to decrease oxidative metabolism significantly. These studies resulting in the discovery of once daily sGC stimulator vericiguat (compound 24, BAY 1021189), currently in phase 3 trials for chronic heart failure, are now reported.

  DOI：

  10.1021/acs.jmedchem.7b00449