1-[4-[[(2S)-2-amino-3-hydroxy-2-methylpropoxy]methyl]-3-methylphenyl]-4-(4-methylphenyl)butan-1-one

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 1-[4-[[(2S)-2-amino-3-hydroxy-2-methylpropoxy]methyl]-3-methylphenyl]-4-(4-methylphenyl)butan-1-one
• 化学式: C₂₃H₃₁NO₃
• 分子量: 369.504
• InChiKey: QPGZCVGPJBNTHP-QHCPKHFHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  27
• 可旋转键数：
  10
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  72.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-[4-[[(2S)-2-amino-3-hydroxy-2-methylpropoxy]methyl]-3-methylphenyl]-4-(4-methylphenyl)butan-1-one 在 盐酸 作用下， 以 1,4-二氧六环 、 乙醇 为溶剂， 反应 1.0h， 生成 1-(4-{[(2S)-2-amino-3-hydroxy-2-methylpropoxy]methyl}-3-methylphenyl)-4-(4-methylphenyl)butan-1-one hydrochloride
  参考文献：
  名称：

  Synthesis and SAR studies of benzyl ether derivatives as potent orally active S1P1 agonists

  摘要：

  We report herein the synthesis and structure-activity relationships (SAR) of a series of benzyl ether compounds as an S1P₁ receptor modulator. From our SAR studies, the installation of substituents onto the central benzene ring of 2a was revealed to potently influence the S1P₁ and S1P₃ agonistic activities, in particular, an ethyl group on the 2-position afforded satisfactory S1P₁/S1P₃ selectivity. These changes of the S1P₁ and S1P₃ agonistic activities caused by the alteration of substituents on the 2-position were reasonably explained by a docking study using an S1P₁ X-ray crystal structure and S1P₃ homology modeling. We found that compounds 2b and 2e had a potent in vivo immunosuppressive efficacy along with acceptable S1P₁/S1P₃ selectivity, and confirmed that these compounds had less in vivo bradycardia risk through the evaluation of heart rate change after oral administration of the compounds (30 mg/kg, p.o.) in rats.

  DOI：

  10.1016/j.bmc.2014.05.035
• 作为产物：
  描述：

  4-溴-1-(溴甲基)-2-甲基苯 在 正丁基锂 、 sodium hydride 、 对甲苯磺酸 、 potassium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 正己烷 、 水 、 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 12.67h， 生成 1-[4-[[(2S)-2-amino-3-hydroxy-2-methylpropoxy]methyl]-3-methylphenyl]-4-(4-methylphenyl)butan-1-one
  参考文献：
  名称：

  Synthesis and SAR studies of benzyl ether derivatives as potent orally active S1P1 agonists

  摘要：

  We report herein the synthesis and structure-activity relationships (SAR) of a series of benzyl ether compounds as an S1P₁ receptor modulator. From our SAR studies, the installation of substituents onto the central benzene ring of 2a was revealed to potently influence the S1P₁ and S1P₃ agonistic activities, in particular, an ethyl group on the 2-position afforded satisfactory S1P₁/S1P₃ selectivity. These changes of the S1P₁ and S1P₃ agonistic activities caused by the alteration of substituents on the 2-position were reasonably explained by a docking study using an S1P₁ X-ray crystal structure and S1P₃ homology modeling. We found that compounds 2b and 2e had a potent in vivo immunosuppressive efficacy along with acceptable S1P₁/S1P₃ selectivity, and confirmed that these compounds had less in vivo bradycardia risk through the evaluation of heart rate change after oral administration of the compounds (30 mg/kg, p.o.) in rats.

  DOI：

  10.1016/j.bmc.2014.05.035