[2-氨基-2-(2-甲氧基-苯基)-乙基]-氨基甲酸叔丁酯盐酸盐 | 939760-42-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 中文名称: [2-氨基-2-(2-甲氧基-苯基)-乙基]-氨基甲酸叔丁酯盐酸盐
• 英文名称: 1,1-dimethylethyl{2-amino-2-[2-(methyloxy)phenyl]ethyl}carbamate
• 英文别名: Tert-butyl 2-amino-2-(2-methoxyphenyl)ethylcarbamate；tert-butyl N-[2-amino-2-(2-methoxyphenyl)ethyl]carbamate
• CAS: 939760-42-6
• 化学式: C₁₄H₂₂N₂O₃
• 分子量: 266.34
• InChiKey: WFJDFZYEBDJNDS-UHFFFAOYSA-N

物化性质

• 沸点：
  416.7±45.0 °C(Predicted)
• 密度：
  1.084±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  19
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  73.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  [2-氨基-2-(2-甲氧基-苯基)-乙基]-氨基甲酸叔丁酯盐酸盐 在 盐酸 、 N,N-二异丙基乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 24.0h， 生成
  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：

  邻甲氧基-2-溴苯乙酮 在 吡啶 、 乌洛托品 、 palladium 10% on activated carbon 、 盐酸羟胺 、 氢气 、 碳酸氢钠 、 sodium iodide 作用下， 以 甲醇 、 乙醇 为溶剂， 反应 49.0h， 生成 [2-氨基-2-(2-甲氧基-苯基)-乙基]-氨基甲酸叔丁酯盐酸盐
  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

• WO2007/76423
  申请人：——

  公开号：——

  公开（公告）日：——
• [EN] INHIBITORS OF Akt ACTIVITY<br/>[FR] INHIBITEURS D'ACTIVITE Akt
  申请人：SMITHKLINE BEECHAM CORP

  公开号：WO2007076423A2

  公开（公告）日：2007-07-05

  [EN] Invented are novel thiophene compounds, the use of such compounds as inhibitors of protein kinase B activity and in the treatment of cancer and arthritis.
  [FR] La présente invention concerne des composés de thiophène atypiques, l'utilisation de tels composés comme inhibiteurs de l'activité de la protéine kinase B et pour le traitement du cancer et de l'arthrite.
• 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.