5-[3-(2-Acetylamino-3H-imidazol-4-yl)-propyl]-4,5-dihydro-isoxazole-3-carboxylic acid ethyl ester | 258845-23-7

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: 5-[3-(2-Acetylamino-3H-imidazol-4-yl)-propyl]-4,5-dihydro-isoxazole-3-carboxylic acid ethyl ester
• CAS: 258845-23-7
• 化学式: C₁₄H₂₀N₄O₄
• 分子量: 308.337
• InChiKey: PRTTZICTUYHTNC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  22.0
• 可旋转键数：
  7.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  105.67
• 氢给体数：
  2.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  5-[3-(2-Acetylamino-3H-imidazol-4-yl)-propyl]-4,5-dihydro-isoxazole-3-carboxylic acid ethyl ester 在 sodium hydroxide 作用下， 以 乙醇 为溶剂， 生成 5-[3-(2-acetylaminoimidazol-4-yl)propyl]isoxazoline-3-carboxylic 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：

  4-(3-ethoxycarbonylisoxazolin-5-yl)butyric acid chloride 在 氢溴酸 作用下， 以 乙醚 、 N,N-二甲基甲酰胺 为溶剂， 反应 98.0h， 生成 5-[3-(2-Acetylamino-3H-imidazol-4-yl)-propyl]-4,5-dihydro-isoxazole-3-carboxylic acid ethyl ester
  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