2-[(1S)-1-amino-2-(4-methoxyphenyl)ethyl]-6-(1H-pyrazol-4-yl)-3H-quinazolin-4-one | 1427310-73-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: 2-[(1S)-1-amino-2-(4-methoxyphenyl)ethyl]-6-(1H-pyrazol-4-yl)-3H-quinazolin-4-one
• CAS: 1427310-73-3
• 化学式: C₂₀H₁₉N₅O₂
• 分子量: 361.403
• InChiKey: IFSJHRROANUFFS-KRWDZBQOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  27
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  105
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  Boc-O-甲基-L-酪氨酸 在 N-甲基吗啉 、 四(三苯基膦)钯 、 potassium carbonate 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 、 三氟乙酸 作用下， 以 乙醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 1.0h， 生成 2-[(1S)-1-amino-2-(4-methoxyphenyl)ethyl]-6-(1H-pyrazol-4-yl)-3H-quinazolin-4-one
  参考文献：
  名称：

  Amino acid derived quinazolines as Rock/PKA inhibitors

  摘要：

  SAR and lead optimization studies for Rock inhibitors based on amino acid-derived quinazolines are described. Studies demonstrated that these amino acid derived quinazolinones were mainly pan-Rock (I & II) inhibitors. While selectivity against other kinases could be achieved, selectivity for most of these compounds against PKA was not achieved. This is distinct from Rock inhibitors based on non-amino acid derived quinazolinones, where high selectivity against PKA could be obtained. 22 The inhibitors presented here in some cases possessed sub-nanomolar inhibition of Rock, nanomolar potency in ppMLC cell based assays, low to fair cytochrome P-450 inhibition, and good human microsomal stability. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.01.109

文献信息

• Amino acid derived quinazolines as Rock/PKA inhibitors
  作者：Sarwat Chowdhury、Yen Ting Chen、Xingang Fang、Wayne Grant、Jennifer Pocas、Michael D. Cameron、Claudia Ruiz、Li Lin、HaJeung Park、Thomas Schröter、Thomas D. Bannister、Philip V. LoGrasso、Yangbo Feng

  DOI：10.1016/j.bmcl.2013.01.109

  日期：2013.3

  SAR and lead optimization studies for Rock inhibitors based on amino acid-derived quinazolines are described. Studies demonstrated that these amino acid derived quinazolinones were mainly pan-Rock (I & II) inhibitors. While selectivity against other kinases could be achieved, selectivity for most of these compounds against PKA was not achieved. This is distinct from Rock inhibitors based on non-amino acid derived quinazolinones, where high selectivity against PKA could be obtained. 22 The inhibitors presented here in some cases possessed sub-nanomolar inhibition of Rock, nanomolar potency in ppMLC cell based assays, low to fair cytochrome P-450 inhibition, and good human microsomal stability. (C) 2013 Elsevier Ltd. All rights reserved.