5-(1-acetyl-5-(3-bromophenyl)-4,5-dihydro-3-pyrazolyl)-2-mercapto-7-methoxybenzoxazole | 1443033-26-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并恶唑类
• 英文名称: 5-(1-acetyl-5-(3-bromophenyl)-4,5-dihydro-3-pyrazolyl)-2-mercapto-7-methoxybenzoxazole
• 英文别名: 1-[3-(3-bromophenyl)-5-(7-methoxy-2-sulfanylidene-3H-1,3-benzoxazol-5-yl)-3,4-dihydropyrazol-2-yl]ethanone
• CAS: 1443033-26-8
• 化学式: C₁₉H₁₆BrN₃O₃S
• 分子量: 446.324
• InChiKey: AYPRFMQDWAKENQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  27
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  95.2
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  1-(5-(3-bromophenyl)-3-(4-hydroxy-3-methoxy-5-nitrophenyl)-4,5-dihydro-1H-pyrazol-1-yl)ethan-1-one 在 sodium dithionite 、 potassium hydroxide 作用下， 以 甲醇 、 水 为溶剂， 反应 3.0h， 生成 5-(1-acetyl-5-(3-bromophenyl)-4,5-dihydro-3-pyrazolyl)-2-mercapto-7-methoxybenzoxazole
  参考文献：
  名称：

  Pharmacophore combination as a useful strategy to discover new antitubercular agents

  摘要：

  The present study is aimed at combining two well-known pharmacophores (pyrazoline and benzoxazole nucleus) to design and synthesize a series of substituted pyrazoline-based benzoxazole derivatives. In vitro antitubercular evaluation against Mycobacterium tuberculosis H37Rv, multidrug-resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB) strains showed that most of the target compounds displayed potent activity (MIC similar to 1.25-25 mu g/mL) where few compounds were found to be better than isoniazid against MDR-TB (MIC = 3.25 mu g/mL) and XDR-TB (MIC = 12.5 mu g/mL). Cytotoxicity assay of these active compounds in VERO cell lines displayed good selectivity index. In order to gain insights into the plausible binding motifs, the target compounds were docked into enoyl-acyl carrier protein reductase, a molecular target of isoniazid. All the docked compounds occupied the same hydrophobic binding pocket and interacted mostly by dispersion interactions. Contribution of the three pharmacophoric fragments (pyrazoline, benzoxazole and aryl ring) toward protein-ligand binding was evaluated at semi empirical quantum mechanics level. The interaction energies suggested that most of the binding was governed by the benzoxaxole moiety followed by pyrazoline and aryl rings.

  DOI：

  10.1007/s00044-013-0645-x

文献信息

• Pharmacophore combination as a useful strategy to discover new antitubercular agents
  作者：Dharmarajsinh N. Rana、Mahesh T. Chhabria、Nisha K. Shah、Pathik S. Brahmkshatriya

  DOI：10.1007/s00044-013-0645-x

  日期：2014.1

  The present study is aimed at combining two well-known pharmacophores (pyrazoline and benzoxazole nucleus) to design and synthesize a series of substituted pyrazoline-based benzoxazole derivatives. In vitro antitubercular evaluation against Mycobacterium tuberculosis H37Rv, multidrug-resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB) strains showed that most of the target compounds displayed potent activity (MIC similar to 1.25-25 mu g/mL) where few compounds were found to be better than isoniazid against MDR-TB (MIC = 3.25 mu g/mL) and XDR-TB (MIC = 12.5 mu g/mL). Cytotoxicity assay of these active compounds in VERO cell lines displayed good selectivity index. In order to gain insights into the plausible binding motifs, the target compounds were docked into enoyl-acyl carrier protein reductase, a molecular target of isoniazid. All the docked compounds occupied the same hydrophobic binding pocket and interacted mostly by dispersion interactions. Contribution of the three pharmacophoric fragments (pyrazoline, benzoxazole and aryl ring) toward protein-ligand binding was evaluated at semi empirical quantum mechanics level. The interaction energies suggested that most of the binding was governed by the benzoxaxole moiety followed by pyrazoline and aryl rings.