N-(4-bromobenzyl)tryptophan methyl ester

• 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-(4-bromobenzyl)tryptophan methyl ester
• 英文别名: methyl (2S)-2-[(4-bromophenyl)methylamino]-3-(1H-indol-3-yl)propanoate
• 化学式: C₁₉H₁₉BrN₂O₂
• 分子量: 387.276
• InChiKey: VMXNVRVLZAHVPY-SFHVURJKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  24
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  54.1
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N-(4-bromobenzyl)tryptophan methyl ester 在 氨 、 三乙胺 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 55.0h， 生成 N-(4-bromobenzyl)-6-((1H-indol-3-yl)methyl)piperazine-2,5-dione
  参考文献：
  名称：

  Design, synthesis, and characterization of piperazinedione-based dual protein inhibitors for both farnesyltransferase and geranylgeranyltransferase-I

  摘要：

  Farnesyltransferase (FTase) and geranylgeranyltransferase type-I (GGTase-I) both catalyze the prenylation of protein substrate containing a typical -CAAX motif at the carboxyl terminus. The inhibitors for these two enzymes have been widely studied as potential cancer chemotherapeutic agents. In the present study, various piperazinedione derivatives were designed and synthesized as a new type of peptide mimetic compounds, which were characterized and found to be dual protein inhibitors for both FTase and GGTase-l. These compounds have similar chemical and physical properties to -CAAX motif of the protein substrate, which may facilitate their transfer to appropriate drug target in vivo. The best inhibitor compound 26b was found to occupy both isoprenoid and peptide substrate binding sites through kinetics and computer molecular docking studies. (C) 2011 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2011.03.007
• 作为产物：
  描述：

  对溴苯甲醛 在 sodium cyanoborohydride 、 N,N-二异丙基乙胺 作用下， 以 1,2-二氯乙烷 为溶剂， 反应 36.0h， 生成 N-(4-bromobenzyl)tryptophan methyl ester
  参考文献：
  名称：

  Synthesis of 2-Thiohydantoins as Somatostatin Subtype 4 Receptor Ligands

  摘要：

  研究人员制备了一系列 2-硫代海因作为体生长抑素亚型 4（sst4）配体。在三乙胺存在下，N-取代-L-色氨酸甲酯与异硫氰酸盐反应，很容易得到目标化合物。在表达体生长抑素受体亚型 2A (sst2A) 和 4 (sst4) 的细胞系中，对 2-thiohydantoins 的结合亲和力进行了评估。与硫脲 NNC-26-9100 (3)相比，所有 2-thiohydantoins 与 sst4 的结合亲和力都较低。将硫脲分子掺入硬度更高的 2-thiohydantoin 核中会导致构象自由度的丧失，从而妨碍与 sst4 的最佳相互作用。

  DOI：

  10.2174/157018012801319445

文献信息

• Design, synthesis, and characterization of piperazinedione-based dual protein inhibitors for both farnesyltransferase and geranylgeranyltransferase-I
  作者：Yuqin Qiao、Jinbo Gao、Yongge Qiu、Long Wu、Fei Guo、Kenneth Kam-Wing Lo、Ding Li

  DOI：10.1016/j.ejmech.2011.03.007

  日期：2011.6

  Farnesyltransferase (FTase) and geranylgeranyltransferase type-I (GGTase-I) both catalyze the prenylation of protein substrate containing a typical -CAAX motif at the carboxyl terminus. The inhibitors for these two enzymes have been widely studied as potential cancer chemotherapeutic agents. In the present study, various piperazinedione derivatives were designed and synthesized as a new type of peptide mimetic compounds, which were characterized and found to be dual protein inhibitors for both FTase and GGTase-l. These compounds have similar chemical and physical properties to -CAAX motif of the protein substrate, which may facilitate their transfer to appropriate drug target in vivo. The best inhibitor compound 26b was found to occupy both isoprenoid and peptide substrate binding sites through kinetics and computer molecular docking studies. (C) 2011 Elsevier Masson SAS. All rights reserved.
• Synthesis of 2-Thiohydantoins as Somatostatin Subtype 4 Receptor Ligands
  作者：Xin Wang、David Mealer、Lacey Rodgers、Karin Sandoval、Ken Witt、Carsten Stidsen、Michael Ankersen、A. Michael Crider

  DOI：10.2174/157018012801319445

  日期：2012.6.1

  A series of 2-thiohydantoins were prepared as somatostatin subtype 4 (sst4) ligands. Reaction of a Nsubstituted- L-tryptophan methyl ester with an isothiocyanate in the presence of triethylamine readily afforded the target compounds. The 2-thiohydantoins were evaluated for binding affinities in cell lines expressing somatostatin receptor subtypes 2A (sst2A) and 4 (sst4). Compared to the thiourea NNC-26-9100 (3), all 2-thiohydantoins demonstrated lower binding affinities at sst4. Incorporation of the thiourea moiety into the more rigid 2-thiohydantoin nucleus leads to a loss of conformational freedom and may prevent optimal interaction with sst4.

  研究人员制备了一系列 2-硫代海因作为体生长抑素亚型 4（sst4）配体。在三乙胺存在下，N-取代-L-色氨酸甲酯与异硫氰酸盐反应，很容易得到目标化合物。在表达体生长抑素受体亚型 2A (sst2A) 和 4 (sst4) 的细胞系中，对 2-thiohydantoins 的结合亲和力进行了评估。与硫脲 NNC-26-9100 (3)相比，所有 2-thiohydantoins 与 sst4 的结合亲和力都较低。将硫脲分子掺入硬度更高的 2-thiohydantoin 核中会导致构象自由度的丧失，从而妨碍与 sst4 的最佳相互作用。