6-(cyclopropylmethyl)-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-(cyclopropylmethyl)-4-hydroxy-3-phenylpyridin-2(1H)-one
• 英文别名: 6-(cyclopropylmethyl)-4-hydroxy-3-phenyl-1H-pyridin-2-one
• 化学式: C₁₅H₁₅NO₂
• 分子量: 241.29
• InChiKey: SOBIPSSRRBEVAO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  49.3
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  二(2,4,6-三氯苯基)苯基丙二酸酯 、 3-amino-4-cyclopropyl-but-2-enoic acid ethyl ester 在 sodium hydroxide 作用下， 以 neat (no solvent) 为溶剂， 反应 1.75h， 以9.8%的产率得到6-(cyclopropylmethyl)-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

• 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。
• 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.