2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-3-(4-(2-(2-((tert-butyldimethylsilyl)oxy)ethylsulfinyl)ethoxy)phenyl)propanoic acid | 1443132-13-5

• 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: 2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-3-(4-(2-(2-((tert-butyldimethylsilyl)oxy)ethylsulfinyl)ethoxy)phenyl)propanoic acid
• 英文别名: (2S)-3-[4-[2-[2-[tert-butyl(dimethyl)silyl]oxyethylsulfinyl]ethoxy]phenyl]-2-(9H-fluoren-9-ylmethoxycarbonylamino)propanoic acid
• CAS: 1443132-13-5
• 化学式: C₃₄H₄₃NO₇SSi
• 分子量: 637.869
• InChiKey: ABZFEMRBQBIJRL-OAKQUNKWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.37
• 重原子数：
  44
• 可旋转键数：
  16
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  130
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-3-(4-(2-((2-((tert-butyldimethylsilyl)oxy)ethyl)thio)ethoxy)phenyl)-propanoic acid 在 叔丁基过氧化氢 、 二氧化硫脲 作用下， 以 癸烷 、 二氯甲烷 为溶剂， 反应 72.0h， 以74%的产率得到2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-3-(4-(2-(2-((tert-butyldimethylsilyl)oxy)ethylsulfinyl)ethoxy)phenyl)propanoic acid
  参考文献：
  名称：

  Interfacial Cavity Filling To Optimize CD4–Mimetic Miniprotein Interactions with HIV-1 Surface Glycoprotein

  摘要：

  Ligand affinities can be optimized by interfacial cavity filling. A hollow (Phe43 cavity) between HIV-1 surface glycoprotein (gp120) and cluster of differentiation 4 (CD4) receptor extends beyond residue phenylalanine 43 of CD4 and cannot be fully accessed by natural amino acids. To increase HIV-1 gp120 affinity for a family of CD4-mimetic miniproteins (miniCD4s), we targeted the gp120 Phe43 cavity with 11 nonnatural phenylalanine derivatives, introduced into a miniCD4 named M48 (1). The best derivative, named M48U12 (13), bound HIV-1 YU2 gp120 with 8 pM affinity and showed potent HIV-1 neutralization. It contained a methylcyclohexyl derivative of 4-aminophenylalanine, and its cocrystal structure. with gp120 revealed the cyclohexane ring buried within the gp120 hydrophobic core but able to assume multiple orientations in the binding pocket, and the aniline nitrogen potentially providing a focus for further improvement Altogether, the results provide a framework for filling the interfacial Phe43 cavity to enhance miniCD4 affinity.

  DOI：

  10.1021/jm4002988