6-((dimethylamino)methyl)-4-hydroxy-3-phenylpyridin-2(1H)-one

• 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: 6-((dimethylamino)methyl)-4-hydroxy-3-phenylpyridin-2(1H)-one
• 英文别名: 6-(dimethylaminomethyl)-4-hydroxy-3-phenyl-1H-pyridin-2-one；6-[(dimethylamino)methyl]-4-hydroxy-3-phenyl-1H-pyridin-2-one
• 化学式: C₁₄H₁₆N₂O₂
• 分子量: 244.293
• InChiKey: WTROVFKLOYGMHY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  52.6
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  在 sodium hydroxide 作用下， 反应 24.0h， 生成 6-((dimethylamino)methyl)-4-hydroxy-3-phenylpyridin-2(1H)-one
  参考文献：
  名称：

  Structure activity relationships of 4-hydroxy-2-pyridones: A novel class of antituberculosis agents

  摘要：

  Pyridone 1 was identified from a high-throughput cell-based phenotypic screen against Mycobacterium tuberculosis (Mtb) including multi-drug resistant tuberculosis (MDR-TB) as a novel anti-TB agent and subsequently optimized series using cell-based Mtb assay. Preliminary structure activity relationship on the isobutyl group with higher cycloalkyl groups at 6-position of pyridone ring has enabled us to significant improvement of potency against Mtb. The lead compound 30j, a dimethylcyclohexyl group on the 6-position of the pyridone, displayed desirable in vitro potency against both drug sensitive and multi-drug resistant TB clinical isolates. In addition, 30j displayed favorable oral pharmacokinetic properties and demonstrated in vivo efficacy in mouse model. These results emphasize the importance of 4-hydroxy-2-pyridones as a new chemotype and further optimization of properties to treat MDR-TB. (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.10.008

文献信息

• Structure activity relationships of 4-hydroxy-2-pyridones: A novel class of antituberculosis agents
  作者：Pearly Shuyi Ng、Ujjini H. Manjunatha、Srinivasa P.S. Rao、Luis R. Camacho、Ngai Ling Ma、Maxime Herve、Christian G. Noble、Anne Goh、Stefan Peukert、Thierry T. Diagana、Paul W. Smith、Ravinder Reddy Kondreddi

  DOI：10.1016/j.ejmech.2015.10.008

  日期：2015.12

  Pyridone 1 was identified from a high-throughput cell-based phenotypic screen against Mycobacterium tuberculosis (Mtb) including multi-drug resistant tuberculosis (MDR-TB) as a novel anti-TB agent and subsequently optimized series using cell-based Mtb assay. Preliminary structure activity relationship on the isobutyl group with higher cycloalkyl groups at 6-position of pyridone ring has enabled us to significant improvement of potency against Mtb. The lead compound 30j, a dimethylcyclohexyl group on the 6-position of the pyridone, displayed desirable in vitro potency against both drug sensitive and multi-drug resistant TB clinical isolates. In addition, 30j displayed favorable oral pharmacokinetic properties and demonstrated in vivo efficacy in mouse model. These results emphasize the importance of 4-hydroxy-2-pyridones as a new chemotype and further optimization of properties to treat MDR-TB. (C) 2015 Elsevier Masson SAS. All rights reserved.