1-(2-chloro-5-(isopropoxymethyl)phenyl)-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-(2-chloro-5-(isopropoxymethyl)phenyl)-4-methylpyrido[4,3-e][1,2,4]triazolo[4,3-a]pyrazine
• 英文别名: 3-[2-Chloro-5-(propan-2-yloxymethyl)phenyl]-7-methyl-2,4,5,8,12-pentazatricyclo[7.4.0.02,6]trideca-1(9),3,5,7,10,12-hexaene；3-[2-chloro-5-(propan-2-yloxymethyl)phenyl]-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: C₁₉H₁₈ClN₅O
• 分子量: 367.838
• InChiKey: CTYOOSCTADWWDM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  26
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  65.2
• 氢给体数：
  0
• 氢受体数：
  5

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-(2-chloro-5-(isopropoxymethyl)phenyl)-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

• 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.