N-(cyclopropylmethyl)hydroxylamine | 435270-11-4

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: N-(cyclopropylmethyl)hydroxylamine
• 英文别名: O-cyclopropylmethylhydroxyamine；cyclopropylmethylhydroxylamine
• CAS: 435270-11-4
• 化学式: C₄H₉NO
• 分子量: 87.1216
• InChiKey: MNWYVVFHNHMOQJ-UHFFFAOYSA-N

物化性质

• 沸点：
  162.1±23.0 °C(Predicted)
• 密度：
  1.080±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.1
• 重原子数：
  6
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  32.3
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  三甲基硅基异氰酸酯 、 N-(cyclopropylmethyl)hydroxylamine 以 四氢呋喃 、 1,4-二氧六环 为溶剂， 反应 1.0h， 生成 N-(cyclopropylmethyl)-N-hydroxyurea
  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：

  cyclopropanecarbaldehyde oxime 在 盐酸 、 吡啶硼烷 作用下， 生成 N-(cyclopropylmethyl)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

• Heterocyclic inhibitors of MEK and methods of use thereof
  申请人：Wallace Eli

  公开号：US20050054701A1

  公开（公告）日：2005-03-10

  Disclosed are compounds of the Formula I and pharmaceutically acceptable salts and prodrugs thereof, wherein R 1 , R 2 , R 7 , R 8 , R 9 and R 10 , W and Y are as defined in the specification. Such compounds are MEK inhibitors and useful in the treatment of hyperproliferative diseases, such as cancer and inflammation, in mammals. Also disclosed are methods of using such compounds in the treatment of hyperproliferative diseases in mammals and pharmaceutical compositions containing such compounds.

  揭示了Formula I的化合物及其药用盐和前药，其中R1、R2、R7、R8、R9和R10、W和Y如规范中所定义。这些化合物是MEK抑制剂，在哺乳动物中用于治疗高增殖性疾病，如癌症和炎症。还公开了在哺乳动物中使用这些化合物治疗高增殖性疾病的方法以及含有这些化合物的药物组合物。
• Method of treating hyperproliferative disorders using heterocyclic inhibitors of MEK
  申请人：Wallace Eli

  公开号：US20060189668A1

  公开（公告）日：2006-08-24

  Disclosed are methods of inhibiting MEK activity, comprising administering to a mammal an effective amount of a compound of Formula I or IV or a solvate or pharmaceutically acceptable salt thereof, wherein R 1 , R 2 , R 7 , R 8 , R 9 , R 10 , W and Y are as defined in the specification. Also disclosed are methods of treating hyperproliferative diseases, such as cancer and inflammation, in mammals, said method comprising administering to a mammal an effective amount of a compound of Formula I or IV.

  本发明公开了一种抑制MEK活性的方法，包括向哺乳动物施用化合物I或IV的有效量，或其溶剂或药学上可接受的盐，其中R1、R2、R7、R8、R9、R10、W和Y如规范中所定义。本发明还公开了一种治疗哺乳动物的高增殖性疾病，如癌症和炎症的方法，该方法包括向哺乳动物施用化合物I或IV的有效量。
• Structure−Activity Relationships of <i>N</i>-Hydroxyurea 5-Lipoxygenase Inhibitors
  作者：Andrew O. Stewart、Pramila A. Bhatia、Jonathan G. Martin、James B. Summers、Karen E. Rodriques、Michael B. Martin、James H. Holms、Jimmie L. Moore、Richard A. Craig、Teodozyj Kolasa、James D. Ratajczyk、Hormoz Mazdiyasni、Francis A. J. Kerdesky、Shari L. DeNinno、Robert G. Maki、Jennifer B. Bouska、Patrick R. Young、Carmine Lanni、Randy L. Bell、George W. Carter、Clint D. W. Brooks

  DOI：10.1021/jm9700474

  日期：1997.6.1

  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.