(2S,3S)-1-[(2S)-2-amino-3-phenylpropanoyl]-3-phenylpyrrolidine-2-carboxamide | 1443120-69-1

• 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,3S)-1-[(2S)-2-amino-3-phenylpropanoyl]-3-phenylpyrrolidine-2-carboxamide
• CAS: 1443120-69-1
• 化学式: C₂₀H₂₃N₃O₂
• 分子量: 337.422
• InChiKey: MDHXNDICWFLLQE-BZSNNMDCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  25
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  89.4
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  Fmoc-L-苯丙氨酸 、 1,2-Pyrrolidinedicarboxylic acid, 3-phenyl-, 1-(9H-fluoren-9-ylmethyl) ester, cis-(9CI) 在 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 N,N-二异丙基乙胺 、 哌啶 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以42%的产率得到(2S,3S)-1-[(2S)-2-amino-3-phenylpropanoyl]-3-phenylpyrrolidine-2-carboxamide
  参考文献：
  名称：

  Constrained H-Phe-Phe-NH₂ Analogues with High Affinity to the Substance P 1–7 Binding Site and with Improved Metabolic Stability and Cell Permeability

  摘要：

  We recently reported the discovery, of H-Phe-Phe-NH2 as a small and high affinity ligand for the substance P 1-7 (SP1-7, H-Arg-Pro-Lys-Pro-Gln-Gln-Phe-OH) specific binding site and its intriguing ability to reduce neuropathic pain. With the overall aim to develop stable and orally bioavailable SP1-7 mimetics, the dipeptide was chosen as a lead compound. Herein the structure activity relationship (SAR) of a set of modified H-Phe-Phe-NH2 analogues is presented together with their potential active uptake by PEPT1 transporter, intestinal permeability, and metabolic stability. Local constraints via peptide backbone methylation or preparation of cyclized analogues based on pyrrolidine were evaluated and were shown to significantly improve the in vitro pharmacokinetic properties. The SAR was rationalized by deriving a plausible binding pose for the high affinity ligands. Rigidification using a 3-phenylpyrrolidine moiety in the C-terminal of H-Phe-Phe-NH2 resulted in high affinity and improved intrinsic clearance and intestinal epithelial permeability.

  DOI：

  10.1021/jm400209h