6-benzyl-2-pyridin-3-yl-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-ol

• 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-3-yl-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-ol
• 英文别名: 6-Benzyl-2-pyridin-3-yl-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-4-ol；6-benzyl-2-pyridin-3-yl-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one
• 化学式: C₁₉H₁₈N₄O
• 分子量: 318.378
• InChiKey: RIWZZBIFYZZDCW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  24
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  57.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  6-benzyl-2-pyridin-3-yl-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-ol 在 三氯氧磷 作用下， 以 乙腈 为溶剂， 反应 2.0h， 以28%的产率得到6-benzyl-4-chloro-2-pyridin-3-yl-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine
  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
• 作为产物：
  描述：

  1-苄基-3-甲氧基羰酰-4-哌啶酮 、 3-甲脒基吡啶盐酸盐 在 sodium methylate 作用下， 以 乙醇 为溶剂， 反应 2.5h， 以76%的产率得到6-benzyl-2-pyridin-3-yl-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-ol
  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

• [EN] 4-AMINO-2-PYRIDO-BICYCLIC PYRIMIDINES AND USE THEREOF AS TOPOISOMERASE II INHIBITORS<br/>[FR] PYRIMIDINES 4-AMINO-2-PYRIDO-BICYCLIQUES ET LEUR UTILISATION EN TANT QU'INHIBITEURS DE LA TOPOISOMÉRASE II
  申请人：FONDAZIONE ST ITALIANO TECNOLOGIA

  公开号：WO2018114700A1

  公开（公告）日：2018-06-28

  The present invention concerns 4-amino-2-pyrido-bicyclic pyrimidines as type II topoisomerase inhibitors and use thereof as medicaments especially in the treatment of cancer. The invention also provides a method for the manufacture of 4- amino-2-pyrido bicyclic pyrimidines.

  本发明涉及4-氨基-2-吡啶双环嘧啶作为II型拓扑异构酶抑制剂及其用途作为药物，特别是在癌症治疗中的用途。该发明还提供了一种制备4-氨基-2-吡啶双环嘧啶的方法。
• 4-amino-2-pyrido-bicyclic pyrimidines and use thereof as topoisomerase II inhibitors
  申请人：FONDAZIONE ISTITUTO ITALIANO DI TECNOLOGIA

  公开号：US10889560B2

  公开（公告）日：2021-01-12

  The present invention concerns 4-amino-2-pyrido-bicyclic pyrimidines of Formula (I) that function as type II topoisomerase inhibitors and their use thereof as medicaments especially in the treatment of cancer. The invention also provides a method for the manufacture of 4-amino-2-pyrido bicyclic pyrimidines of Formula (I).

  本发明涉及作为II型拓扑异构酶抑制剂的式(I)的4-氨基-2-吡啶双环嘧啶及其作为药物的用途，特别是在癌症治疗中的用途。 本发明还提供了一种制造式（I）的4-氨基-2-吡啶双环嘧啶的方法。
• 4-AMINO-2-PYRIDO-BICYCLIC PYRIMIDINES AND USE THEREOF AS TOPOISOMERASE II INHIBITORS
  申请人：Fondazione Istituto Italiano di Tecnologia

  公开号：EP3558964A1

  公开（公告）日：2019-10-30
• 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.