3-bromo-6-isothiocyanato-2-methylpyridine | 1360886-59-4

• 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: 3-bromo-6-isothiocyanato-2-methylpyridine
• CAS: 1360886-59-4
• 化学式: C₇H₅BrN₂S
• 分子量: 229.1
• InChiKey: BRYVCKZNXDDZJV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.89
• 重原子数：
  11.0
• 可旋转键数：
  1.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  25.25
• 氢给体数：
  0.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  2-hydroxy-2-(4-methylthiazol-2-yl)propanehydrazide 、 3-bromo-6-isothiocyanato-2-methylpyridine 以 四氢呋喃 为溶剂， 以93%的产率得到N-(5-bromo-6-methylpyridin-2-yl)-2-(2-hydroxy-2-(4-methylthiazol-2-yl)propanoyl)hydrazine-1-carbothioamide
  参考文献：
  名称：

  Design, Synthesis, and Evaluation of New Thiadiazole-Based Direct Inhibitors of Enoyl Acyl Carrier Protein Reductase (InhA) for the Treatment of Tuberculosis

  摘要：

  Mycobacterial enoyl acyl carrier protein reductase (InhA) is a clinically validated target for the treatment of tuberculosis infections, a disease that still causes the death of at least a million people annually. A known class of potent, direct, and competitive InhA inhibitors based on a tetracyclic thiadiazole structure has been shown to have in vivo activity in murine models of tuberculosis infection. On the basis of this template, we have here explored the medicinal chemistry of truncated analogues that have only three aromatic rings. In particular, compounds 8b, 8d, 8f, 8l, and 8n show interesting features, including low nanomolar InhA IC50, submicromolar antimycobacterial potency, and improved physicochemical profiles in comparison with the tetracyclic analogues. From this series, 8d is identified as having the best balance of potency and properties, whereby the resolved 8d S-enatiomer shows encouraging in vivo efficacy.

  DOI：

  10.1021/jm501029r
• 作为产物：
  描述：

  2-氨基-5-溴-6-甲基吡啶 、 硫光气 在 碳酸氢钠 作用下， 以 二氯甲烷 、 水 为溶剂， 反应 2.0h， 以98%的产率得到3-bromo-6-isothiocyanato-2-methylpyridine
  参考文献：
  名称：

  Design, Synthesis, and Evaluation of New Thiadiazole-Based Direct Inhibitors of Enoyl Acyl Carrier Protein Reductase (InhA) for the Treatment of Tuberculosis

  摘要：

  Mycobacterial enoyl acyl carrier protein reductase (InhA) is a clinically validated target for the treatment of tuberculosis infections, a disease that still causes the death of at least a million people annually. A known class of potent, direct, and competitive InhA inhibitors based on a tetracyclic thiadiazole structure has been shown to have in vivo activity in murine models of tuberculosis infection. On the basis of this template, we have here explored the medicinal chemistry of truncated analogues that have only three aromatic rings. In particular, compounds 8b, 8d, 8f, 8l, and 8n show interesting features, including low nanomolar InhA IC50, submicromolar antimycobacterial potency, and improved physicochemical profiles in comparison with the tetracyclic analogues. From this series, 8d is identified as having the best balance of potency and properties, whereby the resolved 8d S-enatiomer shows encouraging in vivo efficacy.

  DOI：

  10.1021/jm501029r