(S)-2-Benzyloxycarbonylamino-3-{[1-{5-[4-(tert-butoxycarbonyl-isoquinolin-3-yl-amino)-butyl]-4,5-dihydro-isoxazol-3-yl}-1-hydroxy-meth-(E)-ylidene]-amino}-propionic acid tert-butyl ester | 1028277-87-3

• 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: (S)-2-Benzyloxycarbonylamino-3-{[1-{5-[4-(tert-butoxycarbonyl-isoquinolin-3-yl-amino)-butyl]-4,5-dihydro-isoxazol-3-yl}-1-hydroxy-meth-(E)-ylidene]-amino}-propionic acid tert-butyl ester
• 英文别名: tert-butyl (2S)-3-[[5-[4-[isoquinolin-3-yl-[(2-methylpropan-2-yl)oxycarbonyl]amino]butyl]-4,5-dihydro-1,2-oxazole-3-carbonyl]amino]-2-(phenylmethoxycarbonylamino)propanoate
• CAS: 1028277-87-3
• 化学式: C₃₇H₄₇N₅O₈
• 分子量: 689.809
• InChiKey: QEAULLMRZZCUAG-TXDWVUBVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.8
• 重原子数：
  50
• 可旋转键数：
  18
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  158
• 氢给体数：
  2
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  (S)-2-Benzyloxycarbonylamino-3-{[1-{5-[4-(tert-butoxycarbonyl-isoquinolin-3-yl-amino)-butyl]-4,5-dihydro-isoxazol-3-yl}-1-hydroxy-meth-(E)-ylidene]-amino}-propionic acid tert-butyl ester 在 Pd-BaSO₄ 氢气 作用下， 以 甲醇 为溶剂， 20.0 ℃ 、282.69 kPa 条件下， 反应 15.0h， 以0%的产率得到tert-butyl (2S)-2-amino-3-[[5-[4-[isoquinolin-3-yl-[(2-methylpropan-2-yl)oxycarbonyl]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
• 作为产物：
  描述：

  3-ethoxycarbonyl-5-(4-hydroxybutyl)isoxazoline 在 N-甲基吗啉 、 4-二甲氨基吡啶 、 lithium hydroxide 、 草酰氯 、 三乙酰氧基硼氢化钠 、 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 二甲基亚砜 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 52.75h， 生成 (S)-2-Benzyloxycarbonylamino-3-{[1-{5-[4-(tert-butoxycarbonyl-isoquinolin-3-yl-amino)-butyl]-4,5-dihydro-isoxazol-3-yl}-1-hydroxy-meth-(E)-ylidene]-amino}-propionic acid tert-butyl 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