tert-Butyl [2-(hydroxyimino)-2-phenylethyl]carbamate | 912762-45-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: tert-Butyl [2-(hydroxyimino)-2-phenylethyl]carbamate
• 英文别名: tert-butyl N-(2-hydroxyimino-2-phenylethyl)carbamate
• CAS: 912762-45-9
• 化学式: C₁₃H₁₈N₂O₃
• 分子量: 250.298
• InChiKey: OYCHXXYYNVNOEE-UHFFFAOYSA-N

物化性质

• 沸点：
  405.0±28.0 °C(Predicted)
• 密度：
  1.10±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  18
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  70.9
• 氢给体数：
  2
• 氢受体数：
  4

安全信息

• 海关编码：
  2928000090

反应信息

• 作为反应物：
  描述：

  tert-Butyl [2-(hydroxyimino)-2-phenylethyl]carbamate 在 palladium 10% on activated carbon 、 氢气 作用下， 以 甲醇 为溶剂， 反应 5.0h， 以90%的产率得到(2-氨基-2-苯基乙基)-氨基甲酸叔丁酯
  参考文献：
  名称：

  Hit-to-lead evaluation of a novel class of sphingosine 1-phosphate lyase inhibitors

  摘要：

  Inhibition of sphingosine-1-phosphate lyase has recently been proposed as a potential treatment option for inflammatory disorders such as multiple sclerosis, rheumatoid arthritis, and inflammatory bowel disease. In this report we describe our hit-to-lead evaluation of the isoxazolecarboxamide 6, a high-throughput screening hit (in vitro IC50 = 1.0 mu M, cell IC50 = 1.8 mu M), as a novel S1P lyase inhibitor. We were able to establish basic structure-activity relationships around 6 and succeeded in obtaining X-ray structural information which enabled structure-based design. With the discovery of 28, enzyme activity was quickly improved to IC50 = 120 nM and cell potency to IC50 = 230 nM. The main liability in the established isoxazolecarboxamide hit series was determined to be metabolic stability. In particular we identified that future lead-optimization efforts to overcome this problem should focus on blocking the N-dealkylation on the secondary amine. (C) 2016 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2016.03.043
• 作为产物：
  描述：

  (2-氧代-2-苯乙基)-氨基甲酸叔丁酯 在 吡啶 、 盐酸羟胺 作用下， 以 乙醇 为溶剂， 反应 3.0h， 以66%的产率得到tert-Butyl [2-(hydroxyimino)-2-phenylethyl]carbamate
  参考文献：
  名称：

  Hit-to-lead evaluation of a novel class of sphingosine 1-phosphate lyase inhibitors

  摘要：

  Inhibition of sphingosine-1-phosphate lyase has recently been proposed as a potential treatment option for inflammatory disorders such as multiple sclerosis, rheumatoid arthritis, and inflammatory bowel disease. In this report we describe our hit-to-lead evaluation of the isoxazolecarboxamide 6, a high-throughput screening hit (in vitro IC50 = 1.0 mu M, cell IC50 = 1.8 mu M), as a novel S1P lyase inhibitor. We were able to establish basic structure-activity relationships around 6 and succeeded in obtaining X-ray structural information which enabled structure-based design. With the discovery of 28, enzyme activity was quickly improved to IC50 = 120 nM and cell potency to IC50 = 230 nM. The main liability in the established isoxazolecarboxamide hit series was determined to be metabolic stability. In particular we identified that future lead-optimization efforts to overcome this problem should focus on blocking the N-dealkylation on the secondary amine. (C) 2016 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2016.03.043

文献信息

• Hit-to-lead evaluation of a novel class of sphingosine 1-phosphate lyase inhibitors
  作者：Jurgen Dinges、Christopher M. Harris、Grier A. Wallace、Maria A. Argiriadi、Kara L. Queeney、Denise C. Perron、Eric Dominguez、Tegest Kebede、Kelly E. Desino、Hetal Patel、Anil Vasudevan

  DOI：10.1016/j.bmcl.2016.03.043

  日期：2016.5

  Inhibition of sphingosine-1-phosphate lyase has recently been proposed as a potential treatment option for inflammatory disorders such as multiple sclerosis, rheumatoid arthritis, and inflammatory bowel disease. In this report we describe our hit-to-lead evaluation of the isoxazolecarboxamide 6, a high-throughput screening hit (in vitro IC50 = 1.0 mu M, cell IC50 = 1.8 mu M), as a novel S1P lyase inhibitor. We were able to establish basic structure-activity relationships around 6 and succeeded in obtaining X-ray structural information which enabled structure-based design. With the discovery of 28, enzyme activity was quickly improved to IC50 = 120 nM and cell potency to IC50 = 230 nM. The main liability in the established isoxazolecarboxamide hit series was determined to be metabolic stability. In particular we identified that future lead-optimization efforts to overcome this problem should focus on blocking the N-dealkylation on the secondary amine. (C) 2016 Elsevier Ltd. All rights reserved.