N^α-(tert-butyloxycarbonyl)-L-glutamic acid α-tert-butyl ester dicyclohexylamine salt | 86810-13-1

• 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: N^α-(tert-butyloxycarbonyl)-L-glutamic acid α-tert-butyl ester dicyclohexylamine salt
• 英文别名: Boc-L-Glu-OBu^t*DCHA；N-cyclohexylcyclohexanamine;(4S)-5-[(2-methylpropan-2-yl)oxy]-4-[(2-methylpropan-2-yl)oxycarbonylamino]-5-oxopentanoic acid
• CAS: 86810-13-1
• 化学式: C₁₂H₂₃N*C₁₄H₂₅NO₆
• 分子量: 484.677
• InChiKey: BLKCYTWKXOGZPX-FVGYRXGTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.33
• 重原子数：
  34.0
• 可旋转键数：
  7.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.88
• 拓扑面积：
  113.96
• 氢给体数：
  3.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  N^α-(tert-butyloxycarbonyl)-L-glutamic acid α-tert-butyl ester dicyclohexylamine salt 在 氰基磷酸二乙酯 、 1-羟基苯并三唑 、 N,N-二异丙基乙胺 、 间氯过氧苯甲酸 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 54.0h， 生成 N-α--L-prolyl>-L-phenylalanyl>-N^α-methyl-L-histidyl>-5(S)-amino-6-cyclohexyl-4(S)-hydroxy-2(S)-isopropylhexanoyl>-L-isoleucyl>(1-oxo-2-pyridyl)methylamine
  参考文献：
  名称：

  Renin inhibitory peptides. Incorporation of polar, hydrophilic end groups into an active renin inhibitory peptide template and their evaluation in a human renin-infused rat model and in conscious sodium-depleted monkeys

  摘要：

  We previously reported that Boc-Pro-Phe-N-MeHis-Leu-psi[CHOHCH2]?? -Ile-Amp (1) is a potent and specific inhibitor of human renin in vitro. It was shown to resist degradation by selected proteases and a rat liver homogenate. It was shown to inhibit plasma renin activity and to reduce blood pressure in renin-dependent-animal models both by the intravenous and by the oral routes using dilute citric acid as vehicle. In an effort to discover compounds with improved pharmacological efficacy, we set out to modify the physical characteristics of this highly lipophilic renin inhibitor by incorporation of hydrophilic end groups. We report here a variety of water-solubilizing groups and the resulting structure-activity relationship of these compounds. They all maintain an extremely high level of enzyme inhibitory activity in vitro. Evaluation of these potent renin inhibitors in a human renin infused rat model suggests that some of these compounds exhibit improved pharmacological efficacy in vivo. This observation was further confirmed in the conscious sodium-depleted cynomolgus monkey. Importantly, the oral efficacy was demonstrated in a water vehicle in the absence of citric acid.

  DOI：

  10.1021/jm00106a026

文献信息

• Phosphinyl and Phosphinothioyl Amino Acids and Peptides. VII. The Use of the Dimethylphosphinothioyl Group as a Thiol-protecting Group of Cysteine
  作者：Masaaki Ueki、Kozo Shinozaki

  DOI：10.1246/bcsj.56.1187

  日期：1983.4

  The use of the dimethylphosphinothioyl (Mpt) group for the protection of the thiol function in the cysteine side-chain was studied. N,S-Bis(Mpt)-L-cysteine was obtained directly by means of a Schotten-Baumann-type reaction of Mpt–Cl with L-cysteine. The S–Mpt group was stable under acidic conditions, except for HBr in acetic acid, and it could be removed by treatment with AgNO3 or Hg(OAc)2 in an aqueous

  研究了二甲基膦硫酰基 (Mpt) 基团用于保护半胱氨酸侧链中的硫醇功能的用途。N,S-Bis(Mpt)-L-半胱氨酸通过 Mpt-Cl 与 L-半胱氨酸的 Schotten-Baumann 型反应直接获得。S-Mpt 基团在酸性条件下是稳定的，除了乙酸中的 HBr，它可以通过在水性介质中用 AgNO3 或 Hg(OAc)2 处理来去除。谷胱甘肽是通过利用新的 S-保护基团合成的。
• Synthesis and Structure Activity Relationships of a Novel Antifungal Agent, Azoxybacilin.
  作者：Jun OHWADA、Isao UMEDA、Hitomi ONTSUKA、Yuhko AOKI、Nobuo SHIMMA

  DOI：10.1248/cpb.42.1703

  日期：——

  A new antifungal substance, azoxybacilin (an unusual amino acid with an azoxy moiety) and its derivatives have been synthesized from Boc-L-Asp-OtBu utilizing the Moss procedure for the preparation of the azoxy moiety. The ester derivative, Ro 09-1824, showed more potent antifungal activity and a broader antifungal spectrum than azoxybacilin did.

  一种新的抗真菌物质，阿唑氧巴西林（一种带有阿唑氧基部分的不规则氨基酸）及其衍生物已通过Moss方法从Boc-L-Asp-OtBu合成，旨在制备阿唑氧基部分。酯衍生物Ro 09-1824显示出比阿唑氧巴西林更强的抗真菌活性和更广泛的抗真菌谱。