N-((3-methylthiophen-2-yl)methyl)hydroxylamine

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 杂芳族化合物
• 英文名称: N-((3-methylthiophen-2-yl)methyl)hydroxylamine
• 英文别名: N-[(3-methylthiophen-2-yl)methyl]hydroxylamine
• 化学式: C₆H₉NOS
• 分子量: 143.21
• InChiKey: HOKBGDRBWPANLS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  9
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  60.5
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  三甲基硅基异氰酸酯 、 N-((3-methylthiophen-2-yl)methyl)hydroxylamine 以 四氢呋喃 、 1,4-二氧六环 为溶剂， 反应 1.0h， 生成 N-hydroxy-N-(3-methylthien-2-yl)methyl urea
  参考文献：
  名称：

  Structure−Activity Relationships of N-Hydroxyurea 5-Lipoxygenase Inhibitors

  摘要：

  The discovery of second generation N-hydroxyurea 5-lipoxygenase inhibitors was accomplished through the development of a broad structure-activity relationship (SAR) study. This study identified requirements for improving potency and also extending duration by limiting metabolism. Potency could be maintained by the incorporation of heterocyclic templates substituted with selected lipophilic substituents. Duration of inhibition after oral administration was optimized by identification of structural features in the proximity of the N-hydroxyurea which correlated to low in vitro glucuronidation rates. Furthermore, the rate of in vitro glucuronidation was shown to be stereoselective for certain analogs. (R)-N-[3-[5-(4-Fluorophenoxy)-2-furyl]-1-methyl-2-propynyl]-N-hy- droxyurea (17c) was identified and selected for clinical development.

  DOI：

  10.1021/jm9700474
• 作为产物：
  描述：

  3-methyl-2-thiophenecarboxaldoxime 在 盐酸 、 吡啶硼烷 作用下， 生成 N-((3-methylthiophen-2-yl)methyl)hydroxylamine
  参考文献：
  名称：

  Structure−Activity Relationships of N-Hydroxyurea 5-Lipoxygenase Inhibitors

  摘要：

  The discovery of second generation N-hydroxyurea 5-lipoxygenase inhibitors was accomplished through the development of a broad structure-activity relationship (SAR) study. This study identified requirements for improving potency and also extending duration by limiting metabolism. Potency could be maintained by the incorporation of heterocyclic templates substituted with selected lipophilic substituents. Duration of inhibition after oral administration was optimized by identification of structural features in the proximity of the N-hydroxyurea which correlated to low in vitro glucuronidation rates. Furthermore, the rate of in vitro glucuronidation was shown to be stereoselective for certain analogs. (R)-N-[3-[5-(4-Fluorophenoxy)-2-furyl]-1-methyl-2-propynyl]-N-hy- droxyurea (17c) was identified and selected for clinical development.

  DOI：

  10.1021/jm9700474

文献信息

• RIP1 Inhibitors
  申请人：SIRONAX LTD

  公开号：US20210284598A1

  公开（公告）日：2021-09-16

  The invention provides amides that inhibit cellular necrosis including corresponding sulfonamides, prodrugs and pharmaceutically acceptable salts, hydrates and stereoisomers thereof. The compounds are employed in pharmaceutical compositions, and methods of making and use, including treating a person in need thereof with an effective amount of the compound or composition, and detecting a resultant improvement in the person's health or condition.