Boc-L-Phe-L-His-(3S,4S)-Sta-L-Leu-OCH3 | 87700-33-2

• 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: Boc-L-Phe-L-His-(3S,4S)-Sta-L-Leu-OCH3
• 英文别名: methyl (2S)-2-[[(3S,4S)-3-hydroxy-4-[[(2S)-3-(1H-imidazol-5-yl)-2-[[(2S)-2-[(2-methylpropan-2-yl)oxycarbonylamino]-3-phenylpropanoyl]amino]propanoyl]amino]-6-methylheptanoyl]amino]-4-methylpentanoate
• CAS: 87700-33-2
• 化学式: C₃₅H₅₄N₆O₈
• 分子量: 686.849
• InChiKey: QMIBNDIYLIGQGY-ZIUUJSQJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.56
• 重原子数：
  49.0
• 可旋转键数：
  18.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  200.84
• 氢给体数：
  6.0
• 氢受体数：
  9.0

反应信息

• 作为反应物：
  描述：

  Boc-L-Phe-L-His-(3S,4S)-Sta-L-Leu-OCH3 在 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 tert-butyl N-[(2S)-1-[[(2S)-1-[[(3S,4S)-1-[[(2S)-1-[2-(diaminomethylideneamino)ethylamino]-4-methyl-1-oxopentan-2-yl]amino]-3-hydroxy-6-methyl-1-oxoheptan-4-yl]amino]-3-(1H-imidazol-5-yl)-1-oxopropan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]carbamate
  参考文献：
  名称：

  Renin inhibitors containing hydrophilic groups. Tetrapeptides with enhanced aqueous solubility and nanomolar potency

  摘要：

  Nineteen tetrapeptides containing statine (Sta) and 4-amino-5-cyclohexyl-3-hydroxypentanoic acid (ACHPA) were prepared. Solubility measurements of these compounds were carried out in H2O and in pH 7.4 phosphate buffer solution, and their partition coefficients were determined in a 1:1 1-octanol/sodium phosphate-citric acid buffer system. The tetrapeptides were tested in vitro for their ability to inhibit porcine, canine, and human plasma renins. Four compounds, 6, 12, 14, and 20, were potent inhibitors against all renins tested (IC50 = 10(-9) M). Compound 12 was administered orally to dogs and substantially inhibited plasma renin activity for up to 5 h. The addition of polar groups to the C-terminus of Sta- and ACHPA-containing tetrapeptides renders them soluble in aqueous milieu and provides a valuable tool with which to examine the role of the renin-angiotensin system in physiological and pathological circumstances.

  DOI：

  10.1021/jm00118a009

文献信息

• Renin inhibitors. Statine-containing tetrapeptides with varied hydrophobic carboxy termini
  作者：Mark G. Bock、Robert M. DiPardo、Ben E. Evans、Kenneth E. Rittle、Joshua Boger、Martin Poe、Bruce I. LaMont、Robert J. Lynch、Edgar H. Ulm

  DOI：10.1021/jm00393a029

  日期：1987.10

  A series of statine-containing tetrapeptides, systematically modified at the carboxy terminus with various hydrophobic aromatic groups, is described. These compounds were tested in vitro for their ability to inhibit porcine, human plasma, and purified human kidney renins. These analogues help to define optimal binding aspects in a region of the enzyme that appears to be specific for spatial arrangement of aromatic groups. Replacement of the metabolically labile Phe amide with nonpeptidal groups proved possible while achieving inhibitory potency in the nanomolar range vs. porcine kidney renin. For the compounds 6i, 6m, and 6o, a large discrepancy in potency between the human plasma and the purified human kidney renin assays was observed. This disparity does not appear to be a consequence of a previously proposed plasma binding component.