(2S,2'R,5'R,1''S)-3-[5'-(1''-Benzyloxycarbonylamino-4''-guanidinobutyl)tetrahydrofuran-2'-carbamoyl]-2-benzyloxycarbonylaminopropionic acid trifluoroacetate

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (2S,2'R,5'R,1''S)-3-[5'-(1''-Benzyloxycarbonylamino-4''-guanidinobutyl)tetrahydrofuran-2'-carbamoyl]-2-benzyloxycarbonylaminopropionic acid trifluoroacetate
• 英文别名: [(4S)-4-[(2R,5R)-5-[[(2S)-2-carboxy-2-(phenylmethoxycarbonylamino)ethyl]carbamoyl]oxolan-2-yl]-4-(phenylmethoxycarbonylamino)butyl]-(diaminomethylidene)azanium;2,2,2-trifluoroacetate
• 化学式: C₂HF₃O₂*C₂₉H₃₈N₆O₈
• 分子量: 712.68
• InChiKey: AQYGATFGGRIJQY-ZODOTUICSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.24
• 重原子数：
  50
• 可旋转键数：
  17
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  258
• 氢给体数：
  7
• 氢受体数：
  13

反应信息

• 作为产物：
  描述：

  N-苄氧羰基-N’-叔丁氧羰基-L-鸟氨酸 在 lithium hydroxide 、 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 58.25h， 生成 (2S,2'R,5'R,1''S)-3-[5'-(1''-Benzyloxycarbonylamino-4''-guanidinobutyl)tetrahydrofuran-2'-carbamoyl]-2-benzyloxycarbonylaminopropionic 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

文献信息

• Synthesis and Biological Evaluation of Integrin Antagonists Containingtrans- andcis-2,5-Disubstituted THF Rings
  作者：Frank Osterkamp、Burkhard Ziemer、Ulrich Koert、Matthias Wiesner、Peter Raddatz、Simon L. Goodman

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

  日期：2000.2.18

  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).