[(4-benzyloxyphenylcarbamoyl)methyl]carbamic acid t-butyl ester | 220741-24-2

• 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: [(4-benzyloxyphenylcarbamoyl)methyl]carbamic acid t-butyl ester
• 英文别名: (p-benzyloxyphenylcarbamoyl)methylcarbamic acid tert-butyl ester；[(4-Benzyloxy-phenylcarbamoyl)-methyl]-carbamic acid tert-butyl ester；tert-butyl N-({[4-(benzyloxy)phenyl]carbamoyl}methyl)carbamate；tert-butyl N-[2-oxo-2-(4-phenylmethoxyanilino)ethyl]carbamate
• CAS: 220741-24-2
• 化学式: C₂₀H₂₄N₂O₄
• mdl: MFCD28052801
• 分子量: 356.422
• InChiKey: NGJTVCBTEPRMSB-UHFFFAOYSA-N

物化性质

• 沸点：
  568.4±40.0 °C(Predicted)
• 密度：
  1.179±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  26
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  76.7
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  [(4-benzyloxyphenylcarbamoyl)methyl]carbamic acid t-butyl ester 在 氢气 、 palladium(II) hydroxide 、 三氟乙酸 作用下， 以 甲醇 、 乙醇 、 二氯甲烷 为溶剂， 20.0 ℃ 、101.33 kPa 条件下， 反应 72.0h， 生成 N-[(4-hydroxyphenylcarbamoyl)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：

  BOC-甘氨酸 以 二氯甲烷 为溶剂， 反应 25.0h， 生成 [(4-benzyloxyphenylcarbamoyl)methyl]carbamic acid t-butyl ester
  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

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。
• Calcium channel blockers
  申请人：——

  公开号：US20010023249A1

  公开（公告）日：2001-09-20

  The present invention provides compounds that block calcium channels having the Formula I shown below. 1 The present invention also provides methods of using the compounds of Formula I to treat stroke, cerebral ischemia, head trauma, or epilepsy and to pharmaceutical compositions that contain the compounds of Formula I.

  本发明提供了具有下面式子I的阻断钙通道的化合物。同时，本发明还提供了使用式子I的化合物治疗中风、脑缺血、头部创伤或癫痫的方法，以及含有式子I的制药组合物。
• PHENYLALANINE DERIVATIVES
  申请人：Arnould Jean-Claude

  公开号：US20080045521A1

  公开（公告）日：2008-02-21

  The present invention relates to compounds that inhibit of a5b1 function, processes for their preparation, pharmaceutical compositions containing them as the active ingredient, to their use as medicaments and to their use in the manufacture of medicaments for use in the treatment in warm-blooded animals such as humans of diseases that have a significant angiogenesis or vascular component such as for treatment of solid tumours. The present invention also relates to a5b1 antagonists that also exhibit appropriate selectivity profile(s) against other integrins.

  本发明涉及抑制a5b1功能的化合物，其制备过程，含有其作为活性成分的制药组合物，以及它们作为药物在温血动物（如人类）中治疗具有明显血管生成或血管成分的疾病，例如固体肿瘤的制药用途。本发明还涉及a5b1拮抗剂，其还表现出对其他整合素的适当选择性特征。
• SERINE RACEMASE INHIBITOR
  申请人：National University Corporation University Of Toyama

  公开号：EP2808014A1

  公开（公告）日：2014-12-03

  A novel serine racemase inhibitor exhibits sufficient activity and specificity. The serine racemase inhibitor includes one or more compounds selected from compounds respectively represented by the following general formulas [MM_1], [DR_1], [DR'_1], [LW_1], and [ED_1] as an active ingredient.

  一种新型丝氨酸消旋酶抑制剂具有足够的活性和特异性。丝氨酸消旋酶抑制剂包括一种或多种选自分别由下列通式[MM_1]、[DR_1]、[DR'_1]、[LW_1]和[ED_1]表示的化合物作为活性成分的化合物。
• 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.