N-(R)-phenylglycyl-(R)-1-phenylethylamine | 60656-53-3

• 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-(R)-phenylglycyl-(R)-1-phenylethylamine
• 英文别名: (R)-2-amino-2-phenyl-N-((R)-1-phenylethyl)acetamide；(2R)-2-amino-2-phenyl-N-[(1R)-1-phenylethyl]acetamide
• CAS: 60656-53-3
• 化学式: C₁₆H₁₈N₂O
• 分子量: 254.332
• InChiKey: KOTUCVMGXNNUJL-IUODEOHRSA-N

物化性质

• 熔点：
  112-113 °C(Solv: water (7732-18-5))
• 沸点：
  467.5±45.0 °C(Predicted)
• 密度：
  1.120±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  55.1
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  N-(R)-phenylglycyl-(R)-1-phenylethylamine 在 Alkaligenes faecalis penicillin acylase 作用下， 以 1,4-二氧六环 、 氯仿 、 水 为溶剂， 反应 2.0h， 生成 (R)-2-tert-butoxycarbonylamino-2-phenyl-acetic O-ethyl-carbonic anhydride
  参考文献：
  名称：

  An ‘easy-on, easy-off’ protecting group for the enzymatic resolution of (±)-1-phenylethylamine in an aqueous medium

  摘要：

  A new approach has been developed for the biocatalytic resolution of (+/-)-1-phenylethylamine in 100% aqueous medium based on two integrated enzymatic steps: protection and deprotection of the reactive amine enantiomer catalyzed by the same enzyme-penicillin acylase from Alcaligenes faecalis. An 'easy-on, easy-off' protecting group has been introduced using (R)-phenyl-glycine amide as the acyl donor. (R)-Phenylglycyl-substituted (R)-1-phenylethylamine was poorly soluble and precipitated at enzymatic acylation in an alkaline medium (pH 10-11), driving the synthesis towards high yields. Conversely at pH <7.5, its solubility was continuously increasing, which rendered the subsequent deacylation by the same enzyme highly efficient. In contrast to the resolutions, which employ one biocatalytic step, the new approach made it possible to exploit two sequential enantioselective enzymatic reactions implementing a double enantioselectivity control. Effective enzymatic resolution of (+/-)-1-phenylethylamine in an aqueous medium was performed with (R)-phenyl-glycine amide as an acyl donor using the suggested approach. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetasy.2004.06.051
• 作为产物：
  描述：

  tert-butyl ((R)-2-oxo-1-phenyl-2-(((R)-1-phenylethyl)amino)ethyl)carbamate 在 甲醇 、 乙酰氯 作用下， 以89.7%的产率得到N-(R)-phenylglycyl-(R)-1-phenylethylamine
  参考文献：
  名称：

  Small-Molecule Activator of UNC-51-Like Kinase 1 (ULK1) That Induces Cytoprotective Autophagy for Parkinson’s Disease Treatment

  摘要：

  UNC-51-like kinase 1 (ULK1), the yeast Atg1 ortholog, is the sole serine-threonine kinase and initiating 1, enzyme in autophagy, which may be regarded as a target in Parkinson's disease (PD). Herein, we discovered a small molecule 33i (BL-918) as a potent activator of ULK1 by structure-based drug design. Subsequently, some key amino acid residues (Arg18, Lys50, Asn86, and Tyr89) were found to be crucial to the binding pocket between ULK1 and 33i by site-directed mutagenesis. Moreover, we found that 33i induced autophagy via the ULK complex in SH-SYSY cells. Intriguingly, this activator displayed a cytoprotective effect on MPP+-treated SH-SYSY cells, as well as protected against MPTP-induced motor dysfunction and loss of dopaminergic neurons by targeting ULK1-modulated autophagy in mouse models of PD. Together, these results demonstrate the therapeutic potential to target ULK1, and 33i, the novel activator of ULK1, may serve as a candidate drug for future PD treatment.

  DOI：

  10.1021/acs.jmedchem.7b01575

文献信息

• 靶向自噬激动剂及其在神经退行性疾病治疗 药物中的应用
  申请人：四川大学

  公开号：CN106748892B

  公开（公告）日：2018-09-18

  本发明涉及靶向自噬激动剂及其在神经退行性疾病治疗药物中的应用，属于抗神经退行性疾病药学技术领域。本发明解决的技术问题是提供一种作为ULK1激动剂的化合物。该化合物包括如下所示的化合物或其药学上可接受的盐。本发明的化合物或其药学上可接受的盐，可以作为ULK1激动剂，具有一定的抗神经退行性疾病活性。
• [EN] TARGETED AUTOPHAGY AGONIST AND APPLICATION THEREOF IN TREATMENT OF NEURODEGENERATIVE DISEASES<br/>[FR] AGONISTE D'AUTOPHAGIE CIBLÉ ET SON APPLICATION DANS LE TRAITEMENT DE MALADIES NEURODÉGÉNÉRATIVES<br/>[ZH] 靶向自噬激动剂及其在神经退行性疾病治疗药物中的应用
  申请人：UNIV SICHUAN

  公开号：WO2018133756A1

  公开（公告）日：2018-07-26

  本发明涉及靶向自噬激动剂及其在神经退行性疾病治疗药物中的应用，属于抗神经退行性疾病药学技术领域。本发明解决的技术问题是提供一种作为ULK1激动剂的化合物。该化合物包括如（I）（II）的化合物或其药学上可接受的盐。本发明的化合物或其药学上可接受的盐，可以作为ULK1激动剂，具有一定的抗神经退行性疾病活性。
• Small-Molecule Activator of UNC-51-Like Kinase 1 (ULK1) That Induces Cytoprotective Autophagy for Parkinson’s Disease Treatment
  作者：Liang Ouyang、Lan Zhang、Shouyue Zhang、Dahong Yao、Yuqian Zhao、Guan Wang、Leilei Fu、Peng Lei、Bo Liu

  DOI：10.1021/acs.jmedchem.7b01575

  日期：2018.4.12

  UNC-51-like kinase 1 (ULK1), the yeast Atg1 ortholog, is the sole serine-threonine kinase and initiating 1, enzyme in autophagy, which may be regarded as a target in Parkinson's disease (PD). Herein, we discovered a small molecule 33i (BL-918) as a potent activator of ULK1 by structure-based drug design. Subsequently, some key amino acid residues (Arg18, Lys50, Asn86, and Tyr89) were found to be crucial to the binding pocket between ULK1 and 33i by site-directed mutagenesis. Moreover, we found that 33i induced autophagy via the ULK complex in SH-SYSY cells. Intriguingly, this activator displayed a cytoprotective effect on MPP+-treated SH-SYSY cells, as well as protected against MPTP-induced motor dysfunction and loss of dopaminergic neurons by targeting ULK1-modulated autophagy in mouse models of PD. Together, these results demonstrate the therapeutic potential to target ULK1, and 33i, the novel activator of ULK1, may serve as a candidate drug for future PD treatment.
• An ‘easy-on, easy-off’ protecting group for the enzymatic resolution of (±)-1-phenylethylamine in an aqueous medium
  作者：Dorel T. Guranda、Andrey I. Khimiuk、Luuk M. van Langen、Fred van Rantwijk、Roger A. Sheldon、Vytas K. Švedas

  DOI：10.1016/j.tetasy.2004.06.051

  日期：2004.9

  A new approach has been developed for the biocatalytic resolution of (+/-)-1-phenylethylamine in 100% aqueous medium based on two integrated enzymatic steps: protection and deprotection of the reactive amine enantiomer catalyzed by the same enzyme-penicillin acylase from Alcaligenes faecalis. An 'easy-on, easy-off' protecting group has been introduced using (R)-phenyl-glycine amide as the acyl donor. (R)-Phenylglycyl-substituted (R)-1-phenylethylamine was poorly soluble and precipitated at enzymatic acylation in an alkaline medium (pH 10-11), driving the synthesis towards high yields. Conversely at pH <7.5, its solubility was continuously increasing, which rendered the subsequent deacylation by the same enzyme highly efficient. In contrast to the resolutions, which employ one biocatalytic step, the new approach made it possible to exploit two sequential enantioselective enzymatic reactions implementing a double enantioselectivity control. Effective enzymatic resolution of (+/-)-1-phenylethylamine in an aqueous medium was performed with (R)-phenyl-glycine amide as an acyl donor using the suggested approach. (C) 2004 Elsevier Ltd. All rights reserved.