N-[4-(benzyloxy)phenyl]glycinamide | 938337-87-2

• 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-(benzyloxy)phenyl]glycinamide
• 英文别名: 2-amino-N-(4-phenylmethoxyphenyl)acetamide
• CAS: 938337-87-2
• 化学式: C₁₅H₁₆N₂O₂
• mdl: MFCD00598834
• 分子量: 256.304
• InChiKey: YJPUATSIKWOSST-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  19
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.133
• 拓扑面积：
  64.4
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N-[4-(benzyloxy)phenyl]glycinamide 、 1-Imidazol-1-yl-2-(3-methylphenoxy)ethanone 以 二氯甲烷 为溶剂， 反应 24.0h， 生成 N-[(4-benzyloxyphenylcarbamoyl)methyl]-2-m-tolyloxyacetamide
  参考文献：
  名称：

  In silico and pharmacological screenings identify novel serine racemase inhibitors

  摘要：

  D-Serine is a coagonist of the N-methyl-D-aspartate (NMDA)-type glutamate receptor and its biosynthesis is catalyzed by serine racemase (SR). The overactivation of the NMDA receptor has been implicated in the development of neurodegenerative diseases, strokes, and epileptic seizures, thus, the inhibitors of SR have potential against these pathological states. Here, we have developed novel inhibitors of SR by in silico screening and in vitro enzyme assay. The newly developed inhibitors have lower IC50 value comparing with that of malonate, one of the standard SR inhibitor. The structural features of novel inhibitors suggest the importance of central amide structure having a phenoxy substituent in their structure for the SR inhibitory activity. The present findings suggest the importance and rational development of new drugs for diseases of NMDAR overactivation.

  DOI：

  10.1016/j.bmcl.2014.07.003
• 作为产物：
  描述：

  4-苄氧基苯胺 在 N,N'-羰基二咪唑 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 36.0h， 生成 N-[4-(benzyloxy)phenyl]glycinamide
  参考文献：
  名称：

  A novel serine racemase inhibitor suppresses neuronal over-activation in vivo

  摘要：

  Serine racemase (SRR) is an enzyme that produces o-serine from L-serine. D-Serine acts as an endogenous coagonist of NMDA-type glutamate receptors (NMDARs), which regulate many physiological functions. Over-activation of NMDARs induces excitotoxicity, which is observed in many neurodegenerative disorders and epilepsy states. In our previous works on the generation of SRR gene knockout (Srr-KO) mice and its protective effects against NMDA- and A beta peptide-induced neurodegeneration, we hypothesized that the regulation of NMDARs' over-activation by inhibition of SRR activity is one such therapeutic strategy to combat these disease states. In the previous study, we performed in silico screening to identify four compounds with inhibitory activities against recombinant SRR. Here, we synthesized 21 derivatives of candidate 1, one of four hit compounds, and performed screening by in vitro evaluations. The derivative 13J showed a significantly lower IC50 value in vitro, and suppressed neuronal over-activation in vivo. (C) 2017 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2017.05.011

文献信息

• Synthesis of glutamic acid analogs as potent inhibitors of leukotriene A4 hydrolase
  作者：Thomas A. Kirkland、Marc Adler、John G. Bauman、Ming Chen、Jesper Z. Haeggström、Beverly King、Monica J. Kochanny、Amy M. Liang、Lisa Mendoza、Gary B. Phillips、Marjolein Thunnissen、Lan Trinh、Marc Whitlow、Bin Ye、Hong Ye、John Parkinson、William J. Guilford

  DOI：10.1016/j.bmc.2008.03.042

  日期：2008.5

  Leukotriene B(4) (LTB(4)) is a potent pro-inflammatory mediator that has been implicated in the pathogenesis of multiple diseases, including psoriasis, inflammatory bowel disease, multiple sclerosis and asthma. As a method to decrease the level of LTB(4) and possibly identify novel treatments, inhibitors of the LTB(4) biosynthetic enzyme, leukotriene A(4) hydrolase (LTA(4)-h), have been explored. Here

  白三烯B（4）（LTB（4））是一种有效的促炎介质，已与多种疾病的发病机制有关，包括牛皮癣，炎症性肠病，多发性硬化症和哮喘。作为降低LTB（4）水平并可能确定新疗法的方法，已探索了LTB（4）生物合成酶白三烯A（4）水解酶（LTA（4）-h）的抑制剂。在这里，我们从相应的甘氨酰胺2开始，描述了一种有效的LTA（4）-h抑制剂-谷氨酸4f的芳基酰胺的发现。然后介绍了4f的类似物，重点研究在全血中既有活性又稳定的化合物。这项工作最终确定了符合这些标准的氨基醇12a和氨基酯6b。
• REGULATED BIOCIRCUIT SYSTEMS
  申请人：Obsidian Therapeutics, Inc.

  公开号：US20190192691A1

  公开（公告）日：2019-06-27

  The present invention provides regulatable biocircuit systems. Such systems provide modular and tunable protein expression systems in support of the discovery and development of therapeutic modalities.
• In silico and pharmacological screenings identify novel serine racemase inhibitors
  作者：Hisashi Mori、Ryogo Wada、Jie Li、Tetsuya Ishimoto、Mineyuki Mizuguchi、Takayuki Obita、Hiroaki Gouda、Shuichi Hirono、Naoki Toyooka

  DOI：10.1016/j.bmcl.2014.07.003

  日期：2014.8

  D-Serine is a coagonist of the N-methyl-D-aspartate (NMDA)-type glutamate receptor and its biosynthesis is catalyzed by serine racemase (SR). The overactivation of the NMDA receptor has been implicated in the development of neurodegenerative diseases, strokes, and epileptic seizures, thus, the inhibitors of SR have potential against these pathological states. Here, we have developed novel inhibitors of SR by in silico screening and in vitro enzyme assay. The newly developed inhibitors have lower IC50 value comparing with that of malonate, one of the standard SR inhibitor. The structural features of novel inhibitors suggest the importance of central amide structure having a phenoxy substituent in their structure for the SR inhibitory activity. The present findings suggest the importance and rational development of new drugs for diseases of NMDAR overactivation.
• A novel serine racemase inhibitor suppresses neuronal over-activation in vivo
  作者：Hisashi Mori、Ryogo Wada、Satoyuki Takahara、Yoshikazu Horino、Hironori Izumi、Tetsuya Ishimoto、Tomoyuki Yoshida、Mineyuki Mizuguchi、Takayuki Obita、Hiroaki Gouda、Shuichi Hirono、Naoki Toyooka

  DOI：10.1016/j.bmc.2017.05.011

  日期：2017.7

  Serine racemase (SRR) is an enzyme that produces o-serine from L-serine. D-Serine acts as an endogenous coagonist of NMDA-type glutamate receptors (NMDARs), which regulate many physiological functions. Over-activation of NMDARs induces excitotoxicity, which is observed in many neurodegenerative disorders and epilepsy states. In our previous works on the generation of SRR gene knockout (Srr-KO) mice and its protective effects against NMDA- and A beta peptide-induced neurodegeneration, we hypothesized that the regulation of NMDARs' over-activation by inhibition of SRR activity is one such therapeutic strategy to combat these disease states. In the previous study, we performed in silico screening to identify four compounds with inhibitory activities against recombinant SRR. Here, we synthesized 21 derivatives of candidate 1, one of four hit compounds, and performed screening by in vitro evaluations. The derivative 13J showed a significantly lower IC50 value in vitro, and suppressed neuronal over-activation in vivo. (C) 2017 Elsevier Ltd. All rights reserved.