tert-butyl (2S)-3-(5-(4-(sulfamoylamino)butyl)-4,5-dihydroisoxazole-3-carboxamido)-2-((2,4,6-trimethylphenyl)sulfonamido)propanoate | 258845-20-4

• 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)-3-(5-(4-(sulfamoylamino)butyl)-4,5-dihydroisoxazole-3-carboxamido)-2-((2,4,6-trimethylphenyl)sulfonamido)propanoate
• CAS: 258845-20-4
• 化学式: C₂₄H₃₉N₅O₈S₂
• 分子量: 589.734
• InChiKey: CEHRFKNLUKJZOF-IJHRGXPZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.82
• 重原子数：
  39.0
• 可旋转键数：
  13.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  195.35
• 氢给体数：
  4.0
• 氢受体数：
  9.0

反应信息

• 作为反应物：
  描述：

  tert-butyl (2S)-3-(5-(4-(sulfamoylamino)butyl)-4,5-dihydroisoxazole-3-carboxamido)-2-((2,4,6-trimethylphenyl)sulfonamido)propanoate 在 三氟乙酸 作用下， 反应 1.0h， 以76%的产率得到(2S)-3-[[5-[4-(sulfamoylamino)butyl]-4,5-dihydro-1,2-oxazole-3-carbonyl]amino]-2-[(2,4,6-trimethylphenyl)sulfonylamino]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：

  5-(4-Azido-butyl)-4,5-dihydro-isoxazole-3-carboxylic acid 在 N-甲基吗啉 、 ammonium hydroxide 、 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 三苯基膦 、 叔丁醇 作用下， 以 1,4-二氧六环 、 二氯甲烷 为溶剂， 反应 22.0h， 生成 tert-butyl (2S)-3-(5-(4-(sulfamoylamino)butyl)-4,5-dihydroisoxazole-3-carboxamido)-2-((2,4,6-trimethylphenyl)sulfonamido)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