6-((4,4-dimethylcyclohexyl)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-((4,4-dimethylcyclohexyl)methyl)-4-hydroxy-3-phenylpyridin-2(1H)-one
• 英文别名: NITD-916；6-[(4,4-Dimethylcyclohexyl)methyl]-4-Hydroxy-3-Phenylpyridin-2(1h)-One；6-[(4,4-dimethylcyclohexyl)methyl]-4-hydroxy-3-phenyl-1H-pyridin-2-one
• 化学式: C₂₀H₂₅NO₂
• 分子量: 311.424
• InChiKey: WKDRRKVUJLNFSR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  23
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  49.3
• 氢给体数：
  2
• 氢受体数：
  2

上下游信息

• 上游原料

  中文名称	英文名称	CAS号	化学式	分子量
  ——	2-((4,4-dimethylcyclohexyl)methyl)-4-hydroxy-6-oxo-5-phenyl-1,6-dihydropyridine-3-carboxylic acid ethyl ester	——	C23H29NO4	383.488

• 下游产品

  中文名称	英文名称	CAS号	化学式	分子量
  ——	Dibenzyl (6-((4,4-dimethylcyclohexyl)methyl)-2-oxo-3-phenyl-1,2-dihydropyridin-4-yloxy)methyl phosphate	——	C35H40NO6P	601.7

反应信息

• 作为反应物：
  描述：

  6-((4,4-dimethylcyclohexyl)methyl)-4-hydroxy-3-phenylpyridin-2(1H)-one 、 Dicaesio carbonate 、 二苯基氯甲基磷酸酯 在 乙酸乙酯 、 水 、 Brine 、 Sodium sulfate-III 作用下， 以 N,N-二甲基甲酰胺 、 四氢呋喃 、 tetrahydrofuran N,N-dimethylformamide 、 水 为溶剂， 反应 13.0h， 以to afford 7.5 g of crude dibenzyl (6-((4,4-dimethylcyclohexyl)methyl)-2-oxo-3-phenyl-1,2-dihydropyridin-4-yloxy)methyl phosphate 9的产率得到Dibenzyl (6-((4,4-dimethylcyclohexyl)methyl)-2-oxo-3-phenyl-1,2-dihydropyridin-4-yloxy)methyl phosphate
  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
• 作为产物：
  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

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.
• 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.
• PYRIDONE DERIVATIVES AND USES THEREOF IN THE TREATMENT OF TUBERCULOSIS
  申请人：KONDREDDI Ravinder Reddy

  公开号：US20150291526A1

  公开（公告）日：2015-10-15

  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 Enoyl Acyl Carrier Protein Reductase enzyme (InhA): wherein R 1 , R 2 , R 3 , R 4 and R 5 are as defined herein.

  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。