2,4-Dihydroxy-6-methoxy-5-methyl-(2-methylbutyro)phenon | 55382-32-6

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 2,4-Dihydroxy-6-methoxy-5-methyl-(2-methylbutyro)phenon
• 英文别名: 1-[3-methyl-2-methoxy-4,6-dihydroxybenzene]-2-methylbutan-1-one；Pseudo-aspidinol-2MeB；2',4'-dihydroxy-2,5-dimethyl-6-methoxy-butyrophenone；1-(4,6-dihydroxy-2-methoxy-3-methylphenyl)-2-methylbutan-1-one
• CAS: 55382-32-6
• 化学式: C₁₃H₁₈O₄
• 分子量: 238.284
• InChiKey: JOOXAORQPJVGRF-UHFFFAOYSA-N

物化性质

• 沸点：
  368.7±37.0 °C(Predicted)
• 密度：
  1.145±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.64
• 重原子数：
  17.0
• 可旋转键数：
  4.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  66.76
• 氢给体数：
  2.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  2,4-Dihydroxy-6-methoxy-5-methyl-(2-methylbutyro)phenon 在 potassium carbonate 作用下， 以 丙酮 为溶剂， 生成 1-[2,6-dimethoxy-3-methyl-4-methoxymethoxybenzene]2-methylbutan-1-one
  参考文献：
  名称：

  Derivatives of Natural Product Agrimophol as Disruptors of Intrabacterial pH Homeostasis in Mycobacterium tuberculosis

  摘要：

  This article reports the rational medicinal chemistry of a natural product, agrimophol (1), as a new disruptor of intrabacterial pH (pH(IB)) homeostasis in Mycobacterium tuberculosis (Mtb). Through the systematic investigation of the structure-activity relationship of 1, scaffold-hopping of the diphenylmethane scaffold, pharmacophore displacement strategies, and studies of the structure-metabolism relationship, a new derivative 5a was achieved. Compound 5a showed 100-fold increased potency in the ability to reduce pH(IB) to pH 6.0 and similarly improved mycobactericidal activity compared with 1 against both Mycobacterium bovis-BCG and Mtb. Compound 5a possessed improved metabolic stability in human liver microsomes and hepatocytes, lower cytotoxicity, higher selectivity index, and similar pK(a) value to natural 1. This study introduces a novel scaffold to an old drug, resulting in improved mycobactericidal activity through decreasing pH(IB), and may contribute to the critical search for new agents to overcome drug resistance and persistence in the treatment of tuberculosis.

  DOI：

  10.1021/acsinfecdis.8b00325
• 作为产物：
  描述：

  间苯三酚 在 盐酸 、 aluminum (III) chloride 、 水 、 sodium cyanoborohydride 、 potassium carbonate 、 三氯氧磷 作用下， 以 四氢呋喃 、 甲醇 、 水 、 乙酸乙酯 、 1,2-二氯乙烷 、 丙酮 为溶剂， 生成 2,4-Dihydroxy-6-methoxy-5-methyl-(2-methylbutyro)phenon
  参考文献：
  名称：

  Derivatives of Natural Product Agrimophol as Disruptors of Intrabacterial pH Homeostasis in Mycobacterium tuberculosis

  摘要：

  This article reports the rational medicinal chemistry of a natural product, agrimophol (1), as a new disruptor of intrabacterial pH (pH(IB)) homeostasis in Mycobacterium tuberculosis (Mtb). Through the systematic investigation of the structure-activity relationship of 1, scaffold-hopping of the diphenylmethane scaffold, pharmacophore displacement strategies, and studies of the structure-metabolism relationship, a new derivative 5a was achieved. Compound 5a showed 100-fold increased potency in the ability to reduce pH(IB) to pH 6.0 and similarly improved mycobactericidal activity compared with 1 against both Mycobacterium bovis-BCG and Mtb. Compound 5a possessed improved metabolic stability in human liver microsomes and hepatocytes, lower cytotoxicity, higher selectivity index, and similar pK(a) value to natural 1. This study introduces a novel scaffold to an old drug, resulting in improved mycobactericidal activity through decreasing pH(IB), and may contribute to the critical search for new agents to overcome drug resistance and persistence in the treatment of tuberculosis.

  DOI：

  10.1021/acsinfecdis.8b00325

文献信息

• Derivatives of Natural Product Agrimophol as Disruptors of Intrabacterial pH Homeostasis in <i>Mycobacterium tuberculosis</i>
  作者：Jie Wu、Ran Mu、Mingna Sun、Nan Zhao、Miaomiao Pan、Hongshuang Li、Yi Dong、Zhaogang Sun、Jie Bai、Minwan Hu、Carl F. Nathan、Babak Javid、Gang Liu

  DOI：10.1021/acsinfecdis.8b00325

  日期：2019.7.12

  This article reports the rational medicinal chemistry of a natural product, agrimophol (1), as a new disruptor of intrabacterial pH (pH(IB)) homeostasis in Mycobacterium tuberculosis (Mtb). Through the systematic investigation of the structure-activity relationship of 1, scaffold-hopping of the diphenylmethane scaffold, pharmacophore displacement strategies, and studies of the structure-metabolism relationship, a new derivative 5a was achieved. Compound 5a showed 100-fold increased potency in the ability to reduce pH(IB) to pH 6.0 and similarly improved mycobactericidal activity compared with 1 against both Mycobacterium bovis-BCG and Mtb. Compound 5a possessed improved metabolic stability in human liver microsomes and hepatocytes, lower cytotoxicity, higher selectivity index, and similar pK(a) value to natural 1. This study introduces a novel scaffold to an old drug, resulting in improved mycobactericidal activity through decreasing pH(IB), and may contribute to the critical search for new agents to overcome drug resistance and persistence in the treatment of tuberculosis.