(S)-11-(((9H-fluoren-9-yl)methoxy)carbonyl)-12-isopropyl-2,5,8-trioxa-11-azatridecan-13-oic acid | 1446700-09-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 芴
• 英文名称: (S)-11-(((9H-fluoren-9-yl)methoxy)carbonyl)-12-isopropyl-2,5,8-trioxa-11-azatridecan-13-oic acid
• CAS: 1446700-09-9
• 化学式: C₂₇H₃₅NO₇
• 分子量: 485.577
• InChiKey: ZNCJKXBDVTYKES-VWLOTQADSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.03
• 重原子数：
  35.0
• 可旋转键数：
  14.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  94.53
• 氢给体数：
  1.0
• 氢受体数：
  6.0

反应信息

• 作为产物：
  描述：

  2-[2-(2-甲氧基乙氧基)乙氧基]乙醛 在 sodium cyanoborohydride 、 溶剂黄146 、 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 生成 (S)-11-(((9H-fluoren-9-yl)methoxy)carbonyl)-12-isopropyl-2,5,8-trioxa-11-azatridecan-13-oic acid
  参考文献：
  名称：

  Tackling Lipophilicity of Peptide Drugs: Replacement of the Backbone N-Methyl Group of Cilengitide by N-Oligoethylene Glycol (N-OEG) Chains

  摘要：

  Cilengitide is an RGD-peptide of sequence cyclo[RGDfNMeV] that was was developed as a highly active and selective ligand for the αvβ3 and αvβ5 integrin receptors. We describe the synthesis of three analogues of this peptide in which the N-Me group has been replaced by N-oligoethylene glycol (N-OEG) chains of increasing size: namely N-OEG2, N-OEG11, and N-OEG23, which are respectively composed of 2, 11, and 23 ethylene oxide monomer units. The different N-OEG cyclopeptides and the original peptide were compared with respect to lipophilicity and biological activity. The N-OEG2 analogue was straightforward to synthesize in solid phase using an Fmoc-N-OEG2 building block. The syntheses of the N-OEG11 and N-OEG23 cyclopeptides are hampered by the increased steric hindrance of the N-substituent, and could only be achieved by segment coupling, which takes place with epimerization and thus requires extensive product purification. All the N-OEG analogues were found to be more hydrophobic than the parent peptide, and their hydrophobicity was systematically enhanced upon increasing the length of the OEG chain. The N-OEG2 cyclopeptide displayed the same capacity as Cilengitide to inhibit the integrin-mediated adhesion of HUVEC endothelial, DAOY gliobastoma, and HT-29 colon cancer cells to their ligands vitronectin and fibrinogen. The N-OEG11 and N-OEG23 analogues also inhibited cell adhesion to these immobilized ligands, but their IC50 values dropped by 1 order of magnitude with respect to the parent peptide. These results indicate that replacement of the backbone N-Me group of Cilengitide by a short N-OEG chain provides a more lipophilic analogue with a similar biological activity. Upon increasing the size of the N-OEG chain, liophilicity is enhanced, but synthetic yields drop and the longer polymer chains may impede targeted binding.

  DOI：

  10.1021/bc4003844