nicotinoyl-Pro-Tyr-Lys(Boc) cholesteryl ester | 214596-55-1

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 类固醇和类固醇衍生物
• 英文名称: nicotinoyl-Pro-Tyr-Lys(Boc) cholesteryl ester
• 英文别名: [(3S,8S,9S,10R,13R,14S,17R)-10,13-dimethyl-17-[(2R)-6-methylheptan-2-yl]-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-3-yl] (2S)-2-[[(2S)-3-(4-hydroxyphenyl)-2-[[(2S)-1-(pyridine-3-carbonyl)pyrrolidine-2-carbonyl]amino]propanoyl]amino]-6-[(2-methylpropan-2-yl)oxycarbonylamino]hexanoate
• CAS: 214596-55-1
• 化学式: C₅₈H₈₅N₅O₈
• 分子量: 980.342
• InChiKey: ABJRIDQUXXHZPM-UOHCQKOXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  11.9
• 重原子数：
  71
• 可旋转键数：
  22
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.69
• 拓扑面积：
  176
• 氢给体数：
  4
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  硫酸二甲酯 、 nicotinoyl-Pro-Tyr-Lys(Boc) cholesteryl ester 以 乙醚 为溶剂， 以91.84%的产率得到trigonellyl-Pro-Tyr-Lys(Boc) cholesteryl ester
  参考文献：
  名称：

  Strategies To Target Kyotorphin Analogues to the Brain

  摘要：

  The design, synthesis, and pharmacological evaluation of brain-targeted chemical delivery systems (CDS) for a kyotorphin analogue (Tyr-Lys) are described. The brain-targeted compound contains the active peptide in a packaged, disguised form, flanked between the lipophilic cholesteryl ester on the C-terminus and the 1,4-dihydrotrigonellyl redox targetor, attached to the N-terminus through strategically selected L-amino acid(s) spacer. It was found that for successful brain targeting, the epsilon-amine of Lys needs to be also converted to a Lipophilic function. Through sequential enzymatic bioactivation, the Tyr-Lys dipeptide is released in a sustained manner, producing significant and prolonged analgesic activity as demonstrated by the rat tail latency test. An alternate strategy was also employed. Lys was replaced by a redox amino acid pair, Nys(+) <-> Nys, the nicotinamide <-> 1,4-dihydronicotinamide analogues of Lys (Nys(+) is 2-amino-6-(3-carbamoyl-1-pyridiniumyl)hexanoic acid). The Nys form is lipophilic and facilitates delivery in addition to the C- and N-terminal lipophilic functions, Enzymatic oxidation to Nys(+) provides the lock-in, followed by removal;of the lipophilic groups, releasing Tyr-Nys(+) from the brain-targeted analogue (BTRA). Nys(+) was shown to be an effective substitution for Arg or Lys. The activities of the CDS and BTRA, respectively,were antagonized by naloxone, supporting the designed brain-targeted processes. The mst potent compound is the two-proline spacer containing CDS (CDS-PP), followed by the BTRA.

  DOI：

  10.1021/jm970715l
• 作为产物：
  描述：

  Fmoc-L-酪氨酸 在 哌啶 、 1-羟基苯并三唑 、 N,N'-二环己基碳二亚胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 121.0h， 生成 nicotinoyl-Pro-Tyr-Lys(Boc) cholesteryl ester
  参考文献：
  名称：

  Strategies To Target Kyotorphin Analogues to the Brain

  摘要：

  The design, synthesis, and pharmacological evaluation of brain-targeted chemical delivery systems (CDS) for a kyotorphin analogue (Tyr-Lys) are described. The brain-targeted compound contains the active peptide in a packaged, disguised form, flanked between the lipophilic cholesteryl ester on the C-terminus and the 1,4-dihydrotrigonellyl redox targetor, attached to the N-terminus through strategically selected L-amino acid(s) spacer. It was found that for successful brain targeting, the epsilon-amine of Lys needs to be also converted to a Lipophilic function. Through sequential enzymatic bioactivation, the Tyr-Lys dipeptide is released in a sustained manner, producing significant and prolonged analgesic activity as demonstrated by the rat tail latency test. An alternate strategy was also employed. Lys was replaced by a redox amino acid pair, Nys(+) <-> Nys, the nicotinamide <-> 1,4-dihydronicotinamide analogues of Lys (Nys(+) is 2-amino-6-(3-carbamoyl-1-pyridiniumyl)hexanoic acid). The Nys form is lipophilic and facilitates delivery in addition to the C- and N-terminal lipophilic functions, Enzymatic oxidation to Nys(+) provides the lock-in, followed by removal;of the lipophilic groups, releasing Tyr-Nys(+) from the brain-targeted analogue (BTRA). Nys(+) was shown to be an effective substitution for Arg or Lys. The activities of the CDS and BTRA, respectively,were antagonized by naloxone, supporting the designed brain-targeted processes. The mst potent compound is the two-proline spacer containing CDS (CDS-PP), followed by the BTRA.

  DOI：

  10.1021/jm970715l

文献信息

• Strategies To Target Kyotorphin Analogues to the Brain
  作者：Pei Chen、Nicholas Bodor、Whei-Mei Wu、Laszlo Prokai

  DOI：10.1021/jm970715l

  日期：1998.9.1

  The design, synthesis, and pharmacological evaluation of brain-targeted chemical delivery systems (CDS) for a kyotorphin analogue (Tyr-Lys) are described. The brain-targeted compound contains the active peptide in a packaged, disguised form, flanked between the lipophilic cholesteryl ester on the C-terminus and the 1,4-dihydrotrigonellyl redox targetor, attached to the N-terminus through strategically selected L-amino acid(s) spacer. It was found that for successful brain targeting, the epsilon-amine of Lys needs to be also converted to a Lipophilic function. Through sequential enzymatic bioactivation, the Tyr-Lys dipeptide is released in a sustained manner, producing significant and prolonged analgesic activity as demonstrated by the rat tail latency test. An alternate strategy was also employed. Lys was replaced by a redox amino acid pair, Nys(+) <-> Nys, the nicotinamide <-> 1,4-dihydronicotinamide analogues of Lys (Nys(+) is 2-amino-6-(3-carbamoyl-1-pyridiniumyl)hexanoic acid). The Nys form is lipophilic and facilitates delivery in addition to the C- and N-terminal lipophilic functions, Enzymatic oxidation to Nys(+) provides the lock-in, followed by removal;of the lipophilic groups, releasing Tyr-Nys(+) from the brain-targeted analogue (BTRA). Nys(+) was shown to be an effective substitution for Arg or Lys. The activities of the CDS and BTRA, respectively,were antagonized by naloxone, supporting the designed brain-targeted processes. The mst potent compound is the two-proline spacer containing CDS (CDS-PP), followed by the BTRA.