tert-butyl N-[(1S)-1-(5-ethynyl-6-oxo-1H-pyrimidin-2-yl)-2-phenylethyl]carbamate | 1428732-48-2

• 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 N-[(1S)-1-(5-ethynyl-6-oxo-1H-pyrimidin-2-yl)-2-phenylethyl]carbamate
• CAS: 1428732-48-2
• 化学式: C₁₉H₂₁N₃O₃
• 分子量: 339.394
• InChiKey: ZEKOAYASSFSVOG-HNNXBMFYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  25
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  79.8
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  tert-butyl N-[(1S)-1-(5-ethynyl-6-oxo-1H-pyrimidin-2-yl)-2-phenylethyl]carbamate 在 三氟乙酸 作用下， 以 甲醇 、 二氯甲烷 、 二甲基亚砜 为溶剂， 生成 6-chloro-N-[(1S)-1-furo[2,3-d]pyrimidin-2-yl-2-phenylethyl]-3,3-dimethyl-2,4-dihydroisoquinolin-1-imine
  参考文献：
  名称：

  Structure-based design of novel dihydroisoquinoline BACE-1 inhibitors that do not engage the catalytic aspartates

  摘要：

  The structure-activity relationship of a series of dihydroisoquinoline BACE-1 inhibitors is described. Application of structure-based design to screening hit 1 yielded sub-micromolar inhibitors. Replacement of the carboxylic acid of 1 was guided by X-ray crystallography, which allowed the replacement of a key water-mediated hydrogen bond. This work culminated in compounds such as 31, which possess good BACE-1 potency, excellent permeability and a low P-gp efflux ratio. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.01.103
• 作为产物：
  描述：

  tert-butyl N-[(1S)-1-(5-iodo-6-oxo-1H-pyrimidin-2-yl)-2-phenylethyl]carbamate 在 甲醇 、 bis-triphenylphosphine-palladium(II) chloride 、 copper(l) iodide 、 potassium carbonate 、 三乙胺 作用下， 反应 0.33h， 生成 tert-butyl N-[(1S)-1-(5-ethynyl-6-oxo-1H-pyrimidin-2-yl)-2-phenylethyl]carbamate
  参考文献：
  名称：

  Structure-based design of novel dihydroisoquinoline BACE-1 inhibitors that do not engage the catalytic aspartates

  摘要：

  The structure-activity relationship of a series of dihydroisoquinoline BACE-1 inhibitors is described. Application of structure-based design to screening hit 1 yielded sub-micromolar inhibitors. Replacement of the carboxylic acid of 1 was guided by X-ray crystallography, which allowed the replacement of a key water-mediated hydrogen bond. This work culminated in compounds such as 31, which possess good BACE-1 potency, excellent permeability and a low P-gp efflux ratio. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.01.103

文献信息

• Structure-based design of novel dihydroisoquinoline BACE-1 inhibitors that do not engage the catalytic aspartates
  作者：Simeon Bowers、Ying-zi Xu、Shendong Yuan、Gary D. Probst、Roy K. Hom、Wayman Chan、Andrei W. Konradi、Hing L. Sham、Yong L. Zhu、Paul Beroza、Hu Pan、Eric Brecht、Nanhua Yao、Julie Lougheed、Danny Tam、Zhao Ren、Lany Ruslim、Michael P. Bova、Dean R. Artis

  DOI：10.1016/j.bmcl.2013.01.103

  日期：2013.4

  The structure-activity relationship of a series of dihydroisoquinoline BACE-1 inhibitors is described. Application of structure-based design to screening hit 1 yielded sub-micromolar inhibitors. Replacement of the carboxylic acid of 1 was guided by X-ray crystallography, which allowed the replacement of a key water-mediated hydrogen bond. This work culminated in compounds such as 31, which possess good BACE-1 potency, excellent permeability and a low P-gp efflux ratio. (C) 2013 Elsevier Ltd. All rights reserved.