N^α-Boc-Phe-N^α-benzylglycine ethyl ester | 211506-73-9

• 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: N^α-Boc-Phe-N^α-benzylglycine ethyl ester
• 英文别名: Boc-Phe-Nphe-OEt；ethyl 2-[benzyl-[(2S)-2-[(2-methylpropan-2-yl)oxycarbonylamino]-3-phenylpropanoyl]amino]acetate
• CAS: 211506-73-9
• 化学式: C₂₅H₃₂N₂O₅
• 分子量: 440.539
• InChiKey: SZWCQVCYUWIVKY-NRFANRHFSA-N

物化性质

• 沸点：
  600.8±55.0 °C(Predicted)
• 密度：
  1.143±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  32
• 可旋转键数：
  12
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  84.9
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N^α-Boc-Phe-N^α-benzylglycine ethyl ester 在 盐酸 、 lithium aluminium tetrahydride 、 TEA 、 potassium carbonate 、 三氟乙酸 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 二氯甲烷 、 乙腈 为溶剂， 反应 49.0h， 生成 1-(4-tert-butyl-3'-hydroxybenzhydryl)-2,4-dibenzylpiperazine dihydrochloride
  参考文献：
  名称：

  Exploring the Structure−Activity Relationships of [1-(4-tert-Butyl-3‘-hydroxy)benzhydryl-4-benzylpiperazine] (SL-3111), A High-Affinity and Selective δ-Opioid Receptor Nonpeptide Agonist Ligand

  摘要：

  SL-3111 [1-(4-tert-butyl-3'-hydroxy)benzhydryl-4-benzylpiperazine] is a de novo designed, high-affinity and selective nonpeptide peptidomimetic agonist of the delta-opioid receptor. In a previous report we had described the unique biological characteristics of this ligand and also a need for further structural evaluation(6). To pursue this, we have introduced a completely different heterocyclic template (2 and 3), which, based on molecular modeling studies, may present the required structural features to properly orient the pharmacophore groups. We also have made more subtle changes to the original piperazine scaffold (5 and 11). The biological activities of these compounds revealed an important participation of the scaffold in the ligand-receptor interaction. To further explore functional diversity on the scaffold, we have maintained the original piperazine ring and introduced four different functionalities at position 2 of the heterocyclic ring (15a-d; a = CH2-O-CH2-Ph; b = Me; c = CH2Ph; d = CH2OH). The biological activities observed for these compounds showed a very interesting trend in terms of the steric effects of the groups introduced at this position. A decrease of almost 2000-fold in affinity and potency at the delta-receptor was observed for 15c compared with 15b. This difference may be explained if we postulate that the bioactive conformation of these peptidomimetics is close to the minimal energy conformations calculated in our study. On the basis of these findings we have realized the importance of this position to further explore and simplify the structure of future generations of peptidomimetic ligands.

  DOI：

  10.1021/jm990337f
• 作为产物：
  描述：

  N-苄基甘氨酸乙酯 、 BOC-L-苯丙氨酸 在 bromo-tris(1-pyrrolidinyl)phosphonium hexafluorophosphate 作用下， 生成 N^α-Boc-Phe-N^α-benzylglycine ethyl ester
  参考文献：
  名称：

  设计，合成和生物活性的有效和选择性生长抑素类似物并入新的类肽残基。

  摘要：

  我们报告了与默克环六肽c [Pro6-Phe7-d-Trp8-Lys9-Thr10-Phe11]，L-363,301相关的化合物的合成，生物活性和构效关系研究（序列中的编号指的是天然生长抑素中残基的位置）。该化合物中的Pro残基被芳烷基类肽残基取代。我们提出一种利用β-甲基手性取代约束类肽侧链构象的新颖方法。我们的研究导致分子显示出对hsst2受体的强力结合和更高的选择性（与L-363，301相比，与hsst3和hsst5受体的结合更弱）。在体内，这些类肽类似物选择性抑制生长激素的释放，但对胰岛素的抑制没有作用。包括与两个独立实验室中的五个重组人生长抑素受体结合的生物测定以及体内抑制生长激素和胰岛素的生物学测定提供了对生长抑素类似物的结构与生物学活性之间关系的了解。我们的研究结果对其他肽类激素和神经递质的研究具有重要意义。

  DOI：

  10.1021/jm970393l

文献信息

• Synthesis and SAR of potent and selective tetrahydropyrazinoisoquinolinone 5-HT2C receptor agonists
  作者：Guohua Zhao、Chet Kwon、Sharon N. Bisaha、Philip D. Stein、Karen A. Rossi、Xueying Cao、Thao Ung、Ginger Wu、Chen-Pin Hung、Sarah E. Malmstrom、Ge Zhang、Qinling Qu、Jinping Gan、William J. Keim、Mary Jane Cullen、Kenneth W. Rohrbach、James Devenny、Mary Ann Pelleymounter、Keith J. Miller、Jeffrey A. Robl

  DOI：10.1016/j.bmcl.2013.04.061

  日期：2013.7

  The 5-HT2C receptor has been implicated as a critical regulator of appetite. Small molecule activation of the 5-HT2C receptor has been shown to affect food intake and regulate body weight gain in rodent models and more recently in human clinical trials. Therefore, 5-HT2C is a well validated target for anti-obesity therapy. The synthesis and structure-activity relationships of a series of novel tetrahydropyrazinoisoquinolinone 5-HT2C receptor agonists are presented. Several members of this series were identified as potent 5-HT2C receptor agonists with high functional selectivity against the 5-HT2A and 5-HT2B receptors and reduced food intake in an acute rat feeding model upon oral dosing. (c) 2013 Elsevier Ltd. All rights reserved.