(6-benzyl-2-pyridin-4-yl-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-yl)[3-(4-methylpiperazin-1-yl)propyl]amine

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: (6-benzyl-2-pyridin-4-yl-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-yl)[3-(4-methylpiperazin-1-yl)propyl]amine
• 英文别名: 6-benzyl-N-[3-(4-methylpiperazin-1-yl)propyl]-2-pyridin-4-yl-7,8-dihydro-5H-pyrido[4,3-d]pyrimidin-4-amine
• 化学式: C₂₇H₃₅N₇
• 分子量: 457.622
• InChiKey: KKFLLWARGPNMPF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  34
• 可旋转键数：
  8
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  60.4
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  4-amidinopyridine hydrochloride 在 吡啶 、 sodium methylate 、 potassium carbonate 作用下， 以 1,4-二氧六环 、 乙醇 为溶剂， 反应 4.5h， 生成 (6-benzyl-2-pyridin-4-yl-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-yl)[3-(4-methylpiperazin-1-yl)propyl]amine
  参考文献：
  名称：

  Novel Hits in the Correction of ΔF508-Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Protein: Synthesis, Pharmacological, and ADME Evaluation of Tetrahydropyrido[4,3-d]pyrimidines for the Potential Treatment of Cystic Fibrosis

  摘要：

  Cystic fibrosis (CF) is a lethal genetic disease caused by mutations of the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR) with a prevalence of the Delta F508 mutation. Whereas the detailed mechanisms underlying disease have yet to be fully elucidated, recent breakthroughs in clinical trials have demonstrated that CFTR dysfunction can be corrected by drug-like molecules. On the basis of this success, a screening campaign was carried out, seeking new drug-like compounds able to rescue Delta F508-CFTR that led to the discovery of a novel series of correctors based on a tetrahydropyrido[4,3-d]pyrimidine core. These molecules proved to be soluble, cell-permeable, and active in a disease relevant functional-assay. The series was then further optimized with emphasis on biological data from multiple cell systems while keeping physicochemical properties under strict control. The pharmacological and ADME profile of this corrector series hold promise for the development of more efficacious compounds to be explored for therapeutic use in CF.

  DOI：

  10.1021/acs.jmedchem.5b00771

文献信息

• Novel Hits in the Correction of ΔF508-Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Protein: Synthesis, Pharmacological, and ADME Evaluation of Tetrahydropyrido[4,3-<i>d</i>]pyrimidines for the Potential Treatment of Cystic Fibrosis
  作者：Elisabetta Pesci、Laura Bettinetti、Paola Fanti、Luis J. V. Galietta、Salvatore La Rosa、Letizia Magnoni、Nicoletta Pedemonte、Gian Luca Sardone、Laura Maccari

  DOI：10.1021/acs.jmedchem.5b00771

  日期：2015.12.24

  Cystic fibrosis (CF) is a lethal genetic disease caused by mutations of the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR) with a prevalence of the Delta F508 mutation. Whereas the detailed mechanisms underlying disease have yet to be fully elucidated, recent breakthroughs in clinical trials have demonstrated that CFTR dysfunction can be corrected by drug-like molecules. On the basis of this success, a screening campaign was carried out, seeking new drug-like compounds able to rescue Delta F508-CFTR that led to the discovery of a novel series of correctors based on a tetrahydropyrido[4,3-d]pyrimidine core. These molecules proved to be soluble, cell-permeable, and active in a disease relevant functional-assay. The series was then further optimized with emphasis on biological data from multiple cell systems while keeping physicochemical properties under strict control. The pharmacological and ADME profile of this corrector series hold promise for the development of more efficacious compounds to be explored for therapeutic use in CF.