tert-butyl (R)-(2-oxo-1-phenyl-2-(o-tolylamino)ethyl)carbamate | 672959-76-1

• 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: tert-butyl (R)-(2-oxo-1-phenyl-2-(o-tolylamino)ethyl)carbamate
• 英文别名: (R)-tert-butyl [1-(2-methylphenylcarbamoyl)-1-phenyl-methyl]-carbamate；tert-butyl N-[(1R)-2-(2-methylanilino)-2-oxo-1-phenylethyl]carbamate
• CAS: 672959-76-1
• 化学式: C₂₀H₂₄N₂O₃
• 分子量: 340.422
• InChiKey: WGAJTISXJGXFRG-QGZVFWFLSA-N

物化性质

• 沸点：
  533.7±50.0 °C(Predicted)
• 密度：
  1.153±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  25
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  67.4
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  tert-butyl (R)-(2-oxo-1-phenyl-2-(o-tolylamino)ethyl)carbamate 在 甲醇 、 乙酰氯 作用下， 以 1,2-二氯乙烷 为溶剂， 反应 4.0h， 生成 (R)-2-((naphthalen-1-ylmethyl)amino)-2-phenyl-N-(o-tolyl)acetamide
  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
• 作为产物：
  描述：

  二碳酸二叔丁酯 在 N-甲基吗啉 、 sodium hydroxide 、 氯甲酸异丁酯 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 4.5h， 生成 tert-butyl (R)-(2-oxo-1-phenyl-2-(o-tolylamino)ethyl)carbamate
  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

• [EN] ARYLGLYCINE DERIVATIVES FOR USE AS GLYCINE TRANSPORT INHIBITORS<br/>[FR] DERIVES D'ARYLGLYCINE UTILISABLES COMME INHIBITEURS DE TRANSPORT DE GLYCINE
  申请人：NPS ALLELIX CORP

  公开号：WO2004022534A1

  公开（公告）日：2004-03-18

  The present invention relates to compounds of Formula (I) and salts solvates and hydrates thereof. The invention further relates to pharmaceutical compositions containing said compounds and methods of treating neurological and neuropsychistric disorders using said compounds.

  本发明涉及式(I)的化合物及其盐、溶剂化物和水合物。该发明进一步涉及含有所述化合物的药物组合物，以及使用所述化合物治疗神经和神经精神障碍的方法。
• Design, synthesis, and insecticidal activities of novel diamide derivatives with alpha‐amino acid subunits
  作者：Rui‐Jia Chen、Jun‐Jie Wang、Li Han、Yu‐Cheng Gu、Zhi‐Ping Xu、Jia‐Gao Cheng、Xu‐Sheng Shao、Xiao‐Yong Xu、Zhong Li

  DOI：10.1002/jhet.4268

  日期：2021.7

  A series of diamide derivatives containing α-amino acids were designed and synthesized. These compounds were evaluated for their insecticidal activities against Plutella xylostella, Mythimna separate, Myzus persicae, and Tetranychus cinnabarinus. Most of the title compounds containing an l-phenylglycine skeleton were endowed with good activities at the concentration of 500 mg·L−1. Compounds (R)-A6

  设计并合成了一系列含有α-氨基酸的二酰胺衍生物。评估了这些化合物对小菜蛾、单独的 Mythimna、桃蚜和红叶螨的杀虫活性。大多数含有l-苯基甘氨酸骨架的标题化合物在500 mg·L -1的浓度下具有良好的活性。化合物( R)-A6显示出作为杀虫先导物的进一步优化的潜在价值，LC 50值为86.8 mg·L -1。
• [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。