(2S,2'S,5'R,1''S)-3-[5'-(1''-Benzyloxycarbonylamino-4''-[N2''',N3'''-bis(tert-butoxycarbonyl)guanidino]butyl)tetrahydrofuran-2'-carbamoyl]-2-butylsulfonylamino methyl propionate | 264198-00-7

• 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: (2S,2'S,5'R,1''S)-3-[5'-(1''-Benzyloxycarbonylamino-4''-[N2''',N3'''-bis(tert-butoxycarbonyl)guanidino]butyl)tetrahydrofuran-2'-carbamoyl]-2-butylsulfonylamino methyl propionate
• 英文别名: (2S,2'S,5'R,1''S)-3-[5'-(1''-Benzyloxycarbonylamino-4''-[N²''',N³'''-bis(tert-butoxycarbonyl)guanidino]butyl)tetrahydrofuran-2'-carbamoyl]-2-butylsulfonylamino methyl propionate
• CAS: 264198-00-7
• 化学式: C₃₆H₅₈N₆O₁₂S
• 分子量: 798.956
• InChiKey: AUYTUZGJJQHKFS-BPXGVECKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.39
• 重原子数：
  55.0
• 可旋转键数：
  17.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  238.15
• 氢给体数：
  5.0
• 氢受体数：
  12.0

反应信息

• 作为反应物：
  描述：

  (2S,2'S,5'R,1''S)-3-[5'-(1''-Benzyloxycarbonylamino-4''-[N2''',N3'''-bis(tert-butoxycarbonyl)guanidino]butyl)tetrahydrofuran-2'-carbamoyl]-2-butylsulfonylamino methyl propionate 在 lithium hydroxide 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 2.33h， 生成 (2S,2'S,5'R,1''S)-3-[5'-(1''-Benzyloxycarbonylamino-4''-guanidinobutyl)tetrahydrofuran-2'-carbamoyl]-2-butylsulfonylaminopropionic acid trifluoroacetate
  参考文献：
  名称：

  Synthesis and Biological Evaluation of Integrin Antagonists Containingtrans- andcis-2,5-Disubstituted THF Rings

  摘要：

  The synthesis of a series of RGD mimetics is described. All compounds consist of a central 2,5-disubstituted tetrahydrofuran core, a variable linker to a guanidino group, and a beta-amino alanine unit to mimic the carboxylic acid. Three types of linkers were investigated: a simple four-atom methylene chain (type A, compounds 14, 15, 16, and 17), a four-atom methylene chain with an additional chiral center, and a nitrogen substituent (type B, compounds 38, 39, and 40), and an amide linker of different length with an additional chiral center (type C, compounds 59, 60, 61 and 62). A variety of compounds were tested as potential integrin antagonists in a receptor binding assay (alpha(IIb)beta(3), alpha(v)beta(3), and alpha(v)beta(5)). The relative and absolute configuration of the chiral centers at the THF ring had a pronounced effect on the binding activity and selectivity Compound 14 proved to be a selective inhibitor of to be a selective inhibitor of to be a selective inhibitor of alpha(IIb)beta(3) (IC50 = 20nM), whereas compound 40 exhibited high activity for binding of alpha(IIb)beta(3) (IC50 = 67 nM) and alpha(v)beta(3) (IC50 = 52 nM).

  DOI：

  10.1002/(sici)1521-3765(20000218)6:4<666::aid-chem666>3.0.co;2-z
• 作为产物：
  描述：

  N-苄氧羰基-N’-叔丁氧羰基-L-鸟氨酸 在 sodium chlorite 、 sodium dihydrogenphosphate 、 草酰氯 、 4-甲基苯磺酸吡啶 、 L-Selectride 、 1-羟基苯并三唑 、 magnesium 、 二甲基亚砜 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 三乙胺 、 N,N-二异丙基乙胺 、 间氯过氧苯甲酸 、 三氟乙酸 、 mercury dichloride 、 N,N'-二异丙基碳二亚胺 作用下， 以 四氢呋喃 、 乙醚 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 叔丁醇 为溶剂， 反应 59.42h， 生成 (2S,2'S,5'R,1''S)-3-[5'-(1''-Benzyloxycarbonylamino-4''-[N2''',N3'''-bis(tert-butoxycarbonyl)guanidino]butyl)tetrahydrofuran-2'-carbamoyl]-2-butylsulfonylamino methyl propionate
  参考文献：
  名称：

  Synthesis and Biological Evaluation of Integrin Antagonists Containingtrans- andcis-2,5-Disubstituted THF Rings

  摘要：

  The synthesis of a series of RGD mimetics is described. All compounds consist of a central 2,5-disubstituted tetrahydrofuran core, a variable linker to a guanidino group, and a beta-amino alanine unit to mimic the carboxylic acid. Three types of linkers were investigated: a simple four-atom methylene chain (type A, compounds 14, 15, 16, and 17), a four-atom methylene chain with an additional chiral center, and a nitrogen substituent (type B, compounds 38, 39, and 40), and an amide linker of different length with an additional chiral center (type C, compounds 59, 60, 61 and 62). A variety of compounds were tested as potential integrin antagonists in a receptor binding assay (alpha(IIb)beta(3), alpha(v)beta(3), and alpha(v)beta(5)). The relative and absolute configuration of the chiral centers at the THF ring had a pronounced effect on the binding activity and selectivity Compound 14 proved to be a selective inhibitor of to be a selective inhibitor of to be a selective inhibitor of alpha(IIb)beta(3) (IC50 = 20nM), whereas compound 40 exhibited high activity for binding of alpha(IIb)beta(3) (IC50 = 67 nM) and alpha(v)beta(3) (IC50 = 52 nM).

  DOI：

  10.1002/(sici)1521-3765(20000218)6:4<666::aid-chem666>3.0.co;2-z