(2S,3S)-2-(9H-Fluoren-9-ylmethoxycarbonylamino)-3-naphthalen-2-yl-butyric acid | 208582-08-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 芴
• 英文名称: (2S,3S)-2-(9H-Fluoren-9-ylmethoxycarbonylamino)-3-naphthalen-2-yl-butyric acid
• 英文别名: (2S,3S)-2-(9H-fluoren-9-ylmethoxycarbonylamino)-3-(2-naphthyl)butanoic acid；(2S,3S)-2-(9H-fluoren-9-ylmethoxycarbonylamino)-3-naphthalen-2-ylbutanoic acid
• CAS: 208582-08-5
• 化学式: C₂₉H₂₅NO₄
• 分子量: 451.522
• InChiKey: JWVGWYBTUATLBK-MYUZEXMDSA-N

物化性质

• 沸点：
  686.1±50.0 °C(Predicted)
• 密度：
  1.272±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  6.2
• 重原子数：
  34
• 可旋转键数：
  7
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  75.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  9-芴甲基-N-琥珀酰亚胺基碳酸酯 、 在 sodium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 (2S,3S)-2-(9H-Fluoren-9-ylmethoxycarbonylamino)-3-naphthalen-2-yl-butyric acid
  参考文献：
  名称：

  Discovery of a Novel Series of Potent and Selective Substrate-Based Inhibitors of p60^c-src Protein Tyrosine Kinase:  Conformational and Topographical Constraints in Peptide Design

  摘要：

  On the basis of the efficient substrate for p60(c-src) protein tyrosine kinase (PTK) YIYGSFK-(NH2 (1) (K-m = 55 mu M) obtained by combinatorial methods, we have designed and synthesized a series of conformationally and topographically constrained substrate-based peptide inhibitors of this enzyme, which showed IC50 values in the low-micromolar range (1-3 mu M). A "rotamer scan" was performed by introducing the four stereoisomers of beta-Me(2')Nal in the postulated interaction site of the peptide inhibitor 23 (IC50 = 1.6 mu M) This substitution led to selective and potent inhibitors of p60(c-src) PTK; however, no substantial difference in potency was observed among them. This and the results;of the "stereochemical scan" performed at residues 2 and 7 of 3 (peptides 19-21), which farm the disulfide bond, may suggest that the enzyme active site does not have rigid topographic requirements and thus is able to achieve important conformational changes to bind the ligand as long as the pharmacophore pattern in the inhibitor is conserved. Two new potent iodo-containing nonphosphorylatable tyrosine analogues were also incorporated into our lead inhibitory sequence 23, producing the most potent inhibitors for p60(c-src) PTK identified thus far in our studies. Compounds 29 and 30 exhibit IC50 values of 0.13 and 0.54 mu M, respectively. Peptide 29 is 420-fold more potent than the parent peptide 1. Selectivity studies of peptides 23-30 toward p60(c-src), Lyn, and Lck PTK showed in general high Lyn/Src and moderate Lck/Src selectivity ratios.We found that the chi(1) space constraints of the specialized amino acids, introduced at position 3 of the peptide lead 23, were not as important as the configuration of the C-alpha, of that residue to recognize the subtle chemical environment surrounding the active site of Src and Lck PTK, as reflected on the obtained Lck/ Src selectivity ratios.

  DOI：

  10.1021/jm9707885