1-(5-butoxypyridin-3-yl)-4-methylpyrido[4,3-e][1,2,4]triazolo[4,3-a]pyrazine

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 1-(5-butoxypyridin-3-yl)-4-methylpyrido[4,3-e][1,2,4]triazolo[4,3-a]pyrazine
• 英文别名: 3-(5-Butoxypyridin-3-yl)-7-methyl-2,4,5,8,12-pentazatricyclo[7.4.0.02,6]trideca-1(9),3,5,7,10,12-hexaene；3-(5-butoxypyridin-3-yl)-7-methyl-2,4,5,8,12-pentazatricyclo[7.4.0.02,6]trideca-1(9),3,5,7,10,12-hexaene
• 化学式: C₁₈H₁₈N₆O
• 分子量: 334.381
• InChiKey: IDPOAJGPSIINOF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  25
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  78.1
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  3,4-二氨基吡啶 在 4-二甲氨基吡啶 、 一水合肼 、 三乙胺 、 lithium chloride 作用下， 以 四氢呋喃 、 二氯甲烷 、 氯仿 、 二甲基亚砜 、 正丁醇 为溶剂， 反应 16.58h， 生成 1-(5-butoxypyridin-3-yl)-4-methylpyrido[4,3-e][1,2,4]triazolo[4,3-a]pyrazine
  参考文献：
  名称：

  Pyrido[4,3-e][1,2,4]triazolo[4,3-a]pyrazines as Selective, Brain Penetrant Phosphodiesterase 2 (PDE2) Inhibitors

  摘要：

  A novel series of pyrido[4,3-e][1,2,4]triazolo-[4,3-a]pyrazines is reported as potent PDE2/PDE10 inhibitors with drug-like properties. Selectivity for PDE2 was obtained by introducing a linear, lipophilic moiety on the meta-position of the phenyl ring pending from the triazole. The SAR and protein flexibility were explored with free energy perturbation calculations. Rat pharmacokinetic data and in vivo receptor p or occupancy data are given for two representative compounds 6 and 12.

  DOI：

  10.1021/ml500463t

文献信息

• Treatment of tachycardia
  申请人：OSLO UNIVERSITY HOSPITAL HF

  公开号：US11419874B2

  公开（公告）日：2022-08-23

  The invention provides compounds which are selective PDE2 inhibitors for use in the treatment of tachycardia or tachyarrhythmia Such compounds are particularly suitable for use in the treatment of any of the following conditions: atrial tachycardia, atrial fibrillation, atrial flutter, paroxysmal supraventricular tachycardia, premature ventricular contractions (PVCs), ventricular fibrillation and ventricular tachycardia, and may be used alone or in combination therapy with other conventional cardiovascular drugs, e.g. beta-blockers. In particular, the invention provides compounds which are selective PDE2 inhibitors for use in the treatment of ventricular tachycardia in patients who are suffering from, or who are at risk of suffering from heart failure, CPVT or long QT syndrome.

  本发明提供了用于治疗心动过速或心动过速性心律失常的选择性 PDE2 抑制剂化合物：心房性心动过速、心房颤动、心房扑动、阵发性室上性心动过速、室性早搏 （PVC）、心室颤动和室性心动过速，可单独使用或与其它常规心血管药物（如 β-受体阻滞剂）联合使用。如β-受体阻滞剂。特别是，本发明提供的化合物是选择性 PDE2 抑制剂，可用于治疗心力衰竭、CPVT 或长 QT 综合征患者的室性心动过速或有此风险的患者的室性心动过速。
• TREATMENT OF TACHYCARDIA
  申请人：OSLO UNIVERSITY HOSPITAL HF

  公开号：US20200345744A1

  公开（公告）日：2020-11-05

  The invention provides compounds which are selective PDE2 inhibitors for use in the treatment of tachycardia or tachyarrhythmia Such compounds are particularly suitable for use in the treatment of any of the following conditions: atrial tachycardia, atrial fibrillation, atrial flutter, paroxysmal supraventricular tachycardia, premature ventricular contractions (PVCs), ventricular fibrillation and ventricular tachycardia, and may be used alone or in combination therapy with other conventional cardiovascular drugs, e.g. beta-blockers. In particular, the invention provides compounds which are selective PDE2 inhibitors for use in the treatment of ventricular tachycardia in patients who are suffering from, or who are at risk of suffering from heart failure, CPVT or long QT syndrome.
• [EN] TREATMENT OF TACHYCARDIA<br/>[FR] TRAITEMENT DE LA TACHYCARDIE
  申请人：OSLO UNIV HOSPITAL HF

  公开号：WO2019101970A1

  公开（公告）日：2019-05-31

  The invention provides compounds which are selective PDE2 inhibitors for use in the treatment of tachycardia or tachyarrhythmia. Such compounds are particularly suitable for use in the treatment of any of the following conditions: atrial tachycardia, atrial fibrillation, atrial flutter, paroxysmal supraventricular tachycardia, premature ventricular contractions (PVCs), ventricular fibrillation and ventricular tachycardia, and may be used alone or in combination therapy with other conventional cardiovascular drugs, e.g. beta-blockers. In particular, the invention provides compounds which are selective PDE2 inhibitors for use in the treatment of ventricular tachycardia in patients who are suffering from, or who are at risk of suffering from heart failure, CPVT or long QT syndrome.
• Pyrido[4,3-<i>e</i>][1,2,4]triazolo[4,3-<i>a</i>]pyrazines as Selective, Brain Penetrant Phosphodiesterase 2 (PDE2) Inhibitors
  作者：Frederik J. R. Rombouts、Gary Tresadern、Peter Buijnsters、Xavier Langlois、Fulgencio Tovar、Thomas B. Steinbrecher、Greet Vanhoof、Marijke Somers、José-Ignacio Andrés、Andrés A. Trabanco

  DOI：10.1021/ml500463t

  日期：2015.3.12

  A novel series of pyrido[4,3-e][1,2,4]triazolo-[4,3-a]pyrazines is reported as potent PDE2/PDE10 inhibitors with drug-like properties. Selectivity for PDE2 was obtained by introducing a linear, lipophilic moiety on the meta-position of the phenyl ring pending from the triazole. The SAR and protein flexibility were explored with free energy perturbation calculations. Rat pharmacokinetic data and in vivo receptor p or occupancy data are given for two representative compounds 6 and 12.