(3S)-3-amino-N-[(2S)-1-amino-1-oxo-3-phenylpropan-2-yl]-4-phenylbutanamide | 839730-17-5

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 肽模拟物
• 英文名称: (3S)-3-amino-N-[(2S)-1-amino-1-oxo-3-phenylpropan-2-yl]-4-phenylbutanamide
• CAS: 839730-17-5
• 化学式: C₁₉H₂₃N₃O₂
• 分子量: 325.411
• InChiKey: LOAUQQLJHDOTCG-IRXDYDNUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  24
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  98.2
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-(4-甲醛基苯基)咪唑 、 (3S)-3-amino-N-[(2S)-1-amino-1-oxo-3-phenylpropan-2-yl]-4-phenylbutanamide 在 3 A molecular sieve 、 sodium cyanoborohydride 作用下， 以 甲醇 为溶剂， 反应 16.0h， 以40%的产率得到(3S)-N-[(2S)-1-amino-1-oxo-3-phenylpropan-2-yl]-3-[(4-imidazol-1-ylphenyl)methylamino]-4-phenylbutanamide
  参考文献：
  名称：

  Solid-phase synthesis and pharmacological evaluation of a library of peptidomimetics as potential farnesyltransferase inhibitors: an approach to new lead compounds

  摘要：

  Oncogenic Ras proteins whose activation is farnesylation by farnesyltransferase have been seen as important targets for novel anticancer drugs. Inhibitors of this enzyme have already been developed as potential anti-cancer drugs, particularly by rational design based on the structure of the CA(1)A(2)X carboxyl terminus of Ras. Synthesis of a peptidomimetics library via solid-phase synthesis using the Multipin (TM) method is described here. The most active hits on cellular assays were resynthesized and enzymatic activity was measured. Compounds A1, A5 and A7 present significant activity on the isolated enzyme (IC50 = 117, 57.3 and 28.5 nM) and their molecular docking in the active site of the enzyme provides details on key interactions with the protein. (c) 2006 Elsevier SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2006.03.017
• 作为产物：
  描述：

  L-苯丙氨酰胺盐酸盐 在 盐酸 、 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 甲醇 、 乙醚 、 二氯甲烷 为溶剂， 反应 22.0h， 生成 (3S)-3-amino-N-[(2S)-1-amino-1-oxo-3-phenylpropan-2-yl]-4-phenylbutanamide
  参考文献：
  名称：

  Solid-phase synthesis and pharmacological evaluation of a library of peptidomimetics as potential farnesyltransferase inhibitors: an approach to new lead compounds

  摘要：

  Oncogenic Ras proteins whose activation is farnesylation by farnesyltransferase have been seen as important targets for novel anticancer drugs. Inhibitors of this enzyme have already been developed as potential anti-cancer drugs, particularly by rational design based on the structure of the CA(1)A(2)X carboxyl terminus of Ras. Synthesis of a peptidomimetics library via solid-phase synthesis using the Multipin (TM) method is described here. The most active hits on cellular assays were resynthesized and enzymatic activity was measured. Compounds A1, A5 and A7 present significant activity on the isolated enzyme (IC50 = 117, 57.3 and 28.5 nM) and their molecular docking in the active site of the enzyme provides details on key interactions with the protein. (c) 2006 Elsevier SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2006.03.017

文献信息

• Synthesis of Chiral α-Amino-diazoketones on Solid Support: An Access to β-Homologated Amino Acid Derivatives
  作者：Jean-Alain Fehrentz、Sonia Cantel、Jean Martinez

  DOI：10.1055/s-2004-835639

  日期：——

  Diazoketone derivatives were obtained on solid support from their corresponding α-amino acids anchored by their N-terminus to the resin. A complete study was performed to optimize the two steps process of this synthesis on solid support: activation of the carboxylic acid function followed by reaction with diazomethane. The obtained diazoketones were then submitted to Wolff rearrangement in the presence of an amine to yield the corresponding ­homologated amides or in the presence of water to yield the corresponding β-homologated amino acids.

  重氮酮衍生物是由相应的δ-氨基酸通过其 N-末端锚定到树脂上而在固体载体上获得的。我们进行了一项完整的研究，以优化在固体载体上合成的两个步骤：先激活羧酸功能，然后与重氮甲烷反应。然后将得到的重氮酮在胺存在下进行沃尔夫重排，得到相应的同源酰胺，或在水存在下得到相应的δ-同源氨基酸。