tert-butyl (2S)-2-[(2,4,6-trimethylphenyl)sulfonylamino]-3-[[5-[4-[(1-tritylimidazol-2-yl)amino]butyl]-4,5-dihydro-1,2-oxazole-3-carbonyl]amino]propanoate | 185563-99-9

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: tert-butyl (2S)-2-[(2,4,6-trimethylphenyl)sulfonylamino]-3-[[5-[4-[(1-tritylimidazol-2-yl)amino]butyl]-4,5-dihydro-1,2-oxazole-3-carbonyl]amino]propanoate
• CAS: 185563-99-9
• 化学式: C₄₆H₅₄N₆O₆S
• 分子量: 819.037
• InChiKey: ABJYIRKMMCODRQ-KFNHLEGPSA-N

物化性质

• 密度：
  1.22±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  8.2
• 重原子数：
  59
• 可旋转键数：
  19
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  161
• 氢给体数：
  3
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  tert-butyl (2S)-2-[(2,4,6-trimethylphenyl)sulfonylamino]-3-[[5-[4-[(1-tritylimidazol-2-yl)amino]butyl]-4,5-dihydro-1,2-oxazole-3-carbonyl]amino]propanoate 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 5.0h， 以73%的产率得到(2S)-2-[(2,4,6-trimethylphenyl)sulfonylamino]-3-[[5-[4-[(1-tritylimidazol-2-yl)amino]butyl]-4,5-dihydro-1,2-oxazole-3-carbonyl]amino]propanoic acid
  参考文献：
  名称：

  Isoxazolines as Potent Antagonists of the Integrin α_vβ₃

  摘要：

  Starting with lead compound 2, we sought to increase the selectivity for alpha(v)beta(3)-mediated cell adhesion by examining the effects of structural changes in both the guanidine mimetic and the substituent alpha to the carboxylate. To prepare some of the desired aminoimidazoles, a novel reductive amination utilizing a trityl-protected aminoimidazole was developed. It was found that guanidine mimetics with a wide range of pK(a)'s were potent antagonists of alpha(v)beta(3). In general, it appeared that an acylated 2-aminoimidazole guanidine mimetic imparted excellent selectivity for alpha(v)beta(3)-mediated adhesion versus alpha(IIb)beta(3)-mediated platelet aggregation, with selectivity of approximately 3 orders of magnitude observed for compounds 3g and 3h. It was also found in this series that the alpha-substituent was required for potent activity and that 2,6-disubstituted arylsulfonamides were optimal. In addition, the selective alpha(v)beta(3) antagonist 3h was found to be a potent inhibitor of alpha(v)beta(3)-mediated cell migration.

  DOI：

  10.1021/jm9900321
• 作为产物：
  描述：

  ethyl 5-(4-oxobutyl)isoxazoline-3-carboxylate 在 lithium hydroxide 、 三乙酰氧基硼氢化钠 、 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 三乙胺 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 48.5h， 生成 tert-butyl (2S)-2-[(2,4,6-trimethylphenyl)sulfonylamino]-3-[[5-[4-[(1-tritylimidazol-2-yl)amino]butyl]-4,5-dihydro-1,2-oxazole-3-carbonyl]amino]propanoate
  参考文献：
  名称：

  Isoxazolines as Potent Antagonists of the Integrin α_vβ₃

  摘要：

  Starting with lead compound 2, we sought to increase the selectivity for alpha(v)beta(3)-mediated cell adhesion by examining the effects of structural changes in both the guanidine mimetic and the substituent alpha to the carboxylate. To prepare some of the desired aminoimidazoles, a novel reductive amination utilizing a trityl-protected aminoimidazole was developed. It was found that guanidine mimetics with a wide range of pK(a)'s were potent antagonists of alpha(v)beta(3). In general, it appeared that an acylated 2-aminoimidazole guanidine mimetic imparted excellent selectivity for alpha(v)beta(3)-mediated adhesion versus alpha(IIb)beta(3)-mediated platelet aggregation, with selectivity of approximately 3 orders of magnitude observed for compounds 3g and 3h. It was also found in this series that the alpha-substituent was required for potent activity and that 2,6-disubstituted arylsulfonamides were optimal. In addition, the selective alpha(v)beta(3) antagonist 3h was found to be a potent inhibitor of alpha(v)beta(3)-mediated cell migration.

  DOI：

  10.1021/jm9900321