Boc-D-Trp(N-pentyl)-OH | 862403-26-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: Boc-D-Trp(N-pentyl)-OH
• 英文别名: (R)-2-t-butoxycarbonylamino-3-(1-pentyl-1H-indol-3-yl)propionic acid；D-Tryptophan, N-[(1,1-dimethylethoxy)carbonyl]-1-pentyl-；(2R)-2-[(2-methylpropan-2-yl)oxycarbonylamino]-3-(1-pentylindol-3-yl)propanoic acid
• CAS: 862403-26-7
• 化学式: C₂₁H₃₀N₂O₄
• 分子量: 374.48
• InChiKey: PIFBIBHHHHKNHE-QGZVFWFLSA-N

物化性质

• 沸点：
  559.9±45.0 °C(Predicted)
• 密度：
  1.13±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  27
• 可旋转键数：
  10
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  80.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  Boc-D-Trp(N-pentyl)-OH 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 生成
  参考文献：
  名称：

  Pentapeptides for the treatment of small cell lung cancer: Optimisation by N ind -alkyl modification of the tryptophan side chain

  摘要：

  The pentapeptide, tert-Prenyl4th-NH2 (DMePhe-DTrp-Phe-DTrp(N-tert-prenyl)-Leu-NH2), has recently been reported by our group to exhibit properties of substance P (SP) antagonist G against small cell lung cancer (SCLC). In this study, we undertook a systematic structure activity investigation to optimise this lead compound to improve its in vitro anti-tumour activity and biocompatibility. A series of D-tryptophan (D-Trp) derivatives were synthesised, with a range of aliphatic N-alkyl chains (methyl to pentyl) on the indole nitrogen (N-ind). These were incorporated into the pentapeptide sequence by substitution of the N-ind-tert-prenylated D-Trp 4th residue with the N-ind-alkylated D-Trp derivatives. These pentapeptides were significantly more potent than tert-Prenyl4th-NH2, with the N-ind-butyl modification generating the most cytotoxic peptides. Compared to tert-Prenyl4th-NH2, a single butyl modification on the 4th D-Trp residue (Butyl4th-NH2) showed a similar to 3 fold enhancement in cytotoxicity in either the chemo-naive H69 or the DMS79 (originating from a patient treated with chemotherapeutics and radiation therapy) SCLC cell lines. In addition, the di-butylated sequence on the 2nd and 4th D-Trp residues (Butyl2nd.4th-NH2) gave similar to 4.5 times higher cytotoxicity against the H69 cell line and a similar to 2 fold increase against the DMS79 cell line, compared to tert-Prenyl4th-NH2. The favoured position for butyl modification was the 4th D-Trp residue, as the Butyl2nd-NH2 peptide gave lower cytotoxicity on both cell lines. Butylated peptide sequences, when exposed to neat mouse plasma for 24 h at 37 degrees C, were found to resist degradation with >80% remaining intact compared to similar to 58% for tert-Prenyl4th-NH2. The degradation pathway in plasma occurs via de-amidation of the C-terminus, confirmed by mass spectrometry and RP-HPLC analysis. The butyl modification also conferred resistance to metabolism when tested using S9 liver fraction from mouse. The optimum analogue responsive against the DMS79 cell line was the Butyl4th-NH2 pentapeptide, which revealed a concentration dependent increase in apoptosis: the level of late apoptotic cells rose from similar to 36% at 2 mu M to similar to 96% at 6 mu M, as determined by flow cytometry, compared to the unmodified peptide that showed no such effect. Concluding, the butyl substitutions offered the best perspective for high cytotoxicity, induction of apoptosis and metabolic compatibility thereby comprising an improved broad spectrum SP antagonist candidate for treatment of SCLC. (C) 2017 The Authors. Published by Elsevier Masson SAS.

  DOI：

  10.1016/j.ejmech.2017.05.053
• 作为产物：
  描述：

  Boc-D-Trp(N-pentyl)-O-pentyl 在 水 、 lithium hydroxide 作用下， 以 四氢呋喃 为溶剂， 以81.8%的产率得到Boc-D-Trp(N-pentyl)-OH
  参考文献：
  名称：

  Pentapeptides for the treatment of small cell lung cancer: Optimisation by N ind -alkyl modification of the tryptophan side chain

  摘要：

  The pentapeptide, tert-Prenyl4th-NH2 (DMePhe-DTrp-Phe-DTrp(N-tert-prenyl)-Leu-NH2), has recently been reported by our group to exhibit properties of substance P (SP) antagonist G against small cell lung cancer (SCLC). In this study, we undertook a systematic structure activity investigation to optimise this lead compound to improve its in vitro anti-tumour activity and biocompatibility. A series of D-tryptophan (D-Trp) derivatives were synthesised, with a range of aliphatic N-alkyl chains (methyl to pentyl) on the indole nitrogen (N-ind). These were incorporated into the pentapeptide sequence by substitution of the N-ind-tert-prenylated D-Trp 4th residue with the N-ind-alkylated D-Trp derivatives. These pentapeptides were significantly more potent than tert-Prenyl4th-NH2, with the N-ind-butyl modification generating the most cytotoxic peptides. Compared to tert-Prenyl4th-NH2, a single butyl modification on the 4th D-Trp residue (Butyl4th-NH2) showed a similar to 3 fold enhancement in cytotoxicity in either the chemo-naive H69 or the DMS79 (originating from a patient treated with chemotherapeutics and radiation therapy) SCLC cell lines. In addition, the di-butylated sequence on the 2nd and 4th D-Trp residues (Butyl2nd.4th-NH2) gave similar to 4.5 times higher cytotoxicity against the H69 cell line and a similar to 2 fold increase against the DMS79 cell line, compared to tert-Prenyl4th-NH2. The favoured position for butyl modification was the 4th D-Trp residue, as the Butyl2nd-NH2 peptide gave lower cytotoxicity on both cell lines. Butylated peptide sequences, when exposed to neat mouse plasma for 24 h at 37 degrees C, were found to resist degradation with >80% remaining intact compared to similar to 58% for tert-Prenyl4th-NH2. The degradation pathway in plasma occurs via de-amidation of the C-terminus, confirmed by mass spectrometry and RP-HPLC analysis. The butyl modification also conferred resistance to metabolism when tested using S9 liver fraction from mouse. The optimum analogue responsive against the DMS79 cell line was the Butyl4th-NH2 pentapeptide, which revealed a concentration dependent increase in apoptosis: the level of late apoptotic cells rose from similar to 36% at 2 mu M to similar to 96% at 6 mu M, as determined by flow cytometry, compared to the unmodified peptide that showed no such effect. Concluding, the butyl substitutions offered the best perspective for high cytotoxicity, induction of apoptosis and metabolic compatibility thereby comprising an improved broad spectrum SP antagonist candidate for treatment of SCLC. (C) 2017 The Authors. Published by Elsevier Masson SAS.

  DOI：

  10.1016/j.ejmech.2017.05.053

文献信息

• Hydroxamic Acid Derivative And Age Generation Inhibitor Containing The Derivative
  申请人：Kakuchi Junji

  公开号：US20080132539A1

  公开（公告）日：2008-06-05

  To provide a novel compound which inhibits the generation of AGE and an AGE generation inhibitor containing the compound. A compound represented by the following formula or a pharmaceutically acceptable salt thereof, a medicinal composition containing the compound or such a salt thereof, and an additive composition containing the compound.

  提供一种新化合物，可抑制AGE的生成，并含有该化合物的AGE生成抑制剂。该化合物由以下公式表示或其药学上可接受的盐，药物组合物包含该化合物或其盐，以及含有该化合物的添加剂组合物。
• HYDROXAMIC ACID DERIVATIVE AND AGE GENERATION INHIBITOR CONTAINING THE DERIVATIVE
  申请人：Kureha Corporation

  公开号：EP1707560A1

  公开（公告）日：2006-10-04

  To provide a novel compound which inhibits the generation of AGE and an AGE generation inhibitor containing the compound. A compound represented by the following formula or a pharmaceutically acceptable salt thereof, a medicinal composition containing the compound or such a salt thereof, and an additive composition containing the compound.

  提供一种抑制 AGE 生成的新型化合物和一种含有该化合物的 AGE 生成抑制剂。一种由下式代表的化合物或其药学上可接受的盐、一种含有该化合物或其盐的药物组合物，以及一种含有该化合物的添加剂组合物。
• EP1707560
  申请人：——

  公开号：——

  公开（公告）日：——