2-((4,4-dimethylcyclohexyl)methyl)-4-hydroxy-6-oxo-5-phenyl-1,6-dihydropyridine-3-carboxylic acid ethyl ester

• 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: 2-((4,4-dimethylcyclohexyl)methyl)-4-hydroxy-6-oxo-5-phenyl-1,6-dihydropyridine-3-carboxylic acid ethyl ester
• 英文别名: ethyl 2-((4,4-dimethylcyclohexyl)methyl)-4-hydroxy-6-oxo-5-phenyl-1,6-dihydropyridine-3-carboxylate；Ethyl 2-((4,4-dimethylcyclohexyl)methyl)-4-hydroxy-6-oxo-5-phenyl-1,6-dihydropyridine-3-carboxylate；ethyl 2-[(4,4-dimethylcyclohexyl)methyl]-4-hydroxy-6-oxo-5-phenyl-1H-pyridine-3-carboxylate
• 化学式: C₂₃H₂₉NO₄
• 分子量: 383.488
• InChiKey: MTAZSKHHBHAXFK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  28
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  75.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-((4,4-dimethylcyclohexyl)methyl)-4-hydroxy-6-oxo-5-phenyl-1,6-dihydropyridine-3-carboxylic acid ethyl ester 在 sodium hydroxide 作用下， 反应 24.0h， 生成 6-((4,4-dimethylcyclohexyl)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
• 作为产物：
  描述：

  二(2,4,6-三氯苯基)苯基丙二酸酯 、 3-amino-4-(4,4-dimethylcyclohexyl)but-2-enoic acid ethyl ester 在 pet ether 作用下， 以 二苯醚-联苯共晶 为溶剂， 反应 0.5h， 以to afford 7.3 g (46%) of ethyl 2-((4,4-dimethylcyclohexyl)methyl)-4-hydroxy-6-oxo-5-phenyl-1,6-dihydropyridine-3-carboxylate as an off-white solid的产率得到2-((4,4-dimethylcyclohexyl)methyl)-4-hydroxy-6-oxo-5-phenyl-1,6-dihydropyridine-3-carboxylic acid ethyl ester
  参考文献：
  名称：

  PYRIDONE DERIVATIVES AND USES THEREOF IN THE TREATMENT OF TUBERCULOSIS

  摘要：

  提供了一种化合物(I)的公式，该化合物已被证明对于治疗由通过抑制M.结核分枝杆菌酰基载体蛋白还原酶酶（InhA）抑制油酰载体蛋白还原酶酶而介导的疾病、紊乱或综合症具有有用的作用：其中R1、R2、R3、R4和R5如此处所定义。

  公开号：

  US20150291526A1

文献信息

• US9546138B2
  申请人：——

  公开号：US9546138B2

  公开（公告）日：2017-01-17
• [EN] PYRIDONE DERIVATIVES AND USES THEREOF IN THE TREATMENT OF TUBERCULOSIS<br/>[FR] DÉRIVÉS DE PYRIDONE ET LEURS UTILISATIONS DANS LE TRAITEMENT DE LA TUBERCULOSE
  申请人：NOVARTIS AG

  公开号：WO2014093606A1

  公开（公告）日：2014-06-19

  A compound of Formula (I) is provided that has been shown to be useful for treating a disease, disorder or syndrome that is mediated by the inhibition of mycolic acid biosynthesis through inhibition of M. tuberculosis EnoyI Acyl Carrier Protein Reductase enzyme (InhA): wherein R1, R2, R3, R4 and R5 are as defined herein.