methyl N-(tert-butoxycarbonyl)-2-nitro-5-phenoxy-L-phenylalaninate | 1258545-26-4

• 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: methyl N-(tert-butoxycarbonyl)-2-nitro-5-phenoxy-L-phenylalaninate
• 英文别名: methyl (2S)-2-[(2-methylpropan-2-yl)oxycarbonylamino]-3-(2-nitro-5-phenoxyphenyl)propanoate
• CAS: 1258545-26-4
• 化学式: C₂₁H₂₄N₂O₇
• 分子量: 416.431
• InChiKey: BMYLHLGVSAZSLP-KRWDZBQOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  30
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  120
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  methyl N-(tert-butoxycarbonyl)-2-nitro-5-phenoxy-L-phenylalaninate 在 5%-palladium/activated carbon 作用下， 以 吡啶 为溶剂， 以77%的产率得到tert-butyl [(3S)-1-hydroxy-2-oxo-6-phenoxy-1,2,3,4-tetrahydroquinolin-3-yl]carbamate
  参考文献：
  名称：

  Structure-Based Design of Irreversible Human KAT II Inhibitors: Discovery of New Potency-Enhancing Interactions

  摘要：

  A series of aryl hydroxamates recently have been disclosed as irreversible inhibitors of kynurenine amino transferase II (KAT II), an enzyme that may play a role in schizophrenia and other psychiatric and neurological disorders. The utilization of structure activity relationships (SAR) in conjunction with X-ray crystallography led to the discovery of hydroxamate 4, a disubstituted analogue that has a significant potency enhancement due to a novel interaction with KAT II. The use of k(inact)/K-i to assess potency was critical for understanding the SAR in this series and for identifying compounds with improved pharmacodynamic profiles.

  DOI：

  10.1021/ml300237v
• 作为产物：
  描述：

  2-溴-4-氟-1-硝基苯 在 caesium carbonate 、 锌 作用下， 以 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 81.42h， 生成 methyl N-(tert-butoxycarbonyl)-2-nitro-5-phenoxy-L-phenylalaninate
  参考文献：
  名称：

  Structure-Based Design of Irreversible Human KAT II Inhibitors: Discovery of New Potency-Enhancing Interactions

  摘要：

  A series of aryl hydroxamates recently have been disclosed as irreversible inhibitors of kynurenine amino transferase II (KAT II), an enzyme that may play a role in schizophrenia and other psychiatric and neurological disorders. The utilization of structure activity relationships (SAR) in conjunction with X-ray crystallography led to the discovery of hydroxamate 4, a disubstituted analogue that has a significant potency enhancement due to a novel interaction with KAT II. The use of k(inact)/K-i to assess potency was critical for understanding the SAR in this series and for identifying compounds with improved pharmacodynamic profiles.

  DOI：

  10.1021/ml300237v

文献信息

• Bicyclic And Tricyclic Compounds As KAT II Inhibitors
  申请人：Claffey Michelle M.

  公开号：US20100324043A1

  公开（公告）日：2010-12-23

  Compounds of Formula X: wherein A, X, Y, Z, R 5 , R 6a , and R 6b are as defined herein, and pharmaceutically acceptable salts thereof, are described as useful for the treatment of cognitive deficits associated with schizophrenia and other neurodegenerative and/or neurological disorders in mammals, including humans.

  化合物X的结构如下：其中A、X、Y、Z、R5、R6a和R6b的定义如本文所述，并且其药用盐被描述为用于治疗与精神分裂症及其他哺乳动物，包括人类，相关的认知缺陷的化合物，以及其他神经退行性和/或神经系统疾病。
• Bicyclic and tricyclic compounds as KAT II inhibitors
  申请人：Pfizer Inc.

  公开号：US08183238B2

  公开（公告）日：2012-05-22

  Compounds of Formula X: wherein A, X, Y, Z, R5, R6a, and R6b are as defined herein, and pharmaceutically acceptable salts thereof, are described as useful for the treatment of cognitive deficits associated with schizophrenia and other neurodegenerative and/or neurological disorders in mammals, including humans.

  化合物X的公式：其中A、X、Y、Z、R5、R6a和R6b的定义如本文所述，并且其药学上可接受的盐，被描述为用于治疗哺乳动物，包括人类，中与精神分裂症和其他神经退行性和/或神经性疾病相关的认知缺陷有关的有用化合物。
• BICYCLIC AND TRICYCLIC COMPOUNDS AS KAT II INHIBITORS
  申请人：Pfizer Inc.

  公开号：EP2443092B1

  公开（公告）日：2015-04-08
• US8183238B2
  申请人：——

  公开号：US8183238B2

  公开（公告）日：2012-05-22
• Structure-Based Design of Irreversible Human KAT II Inhibitors: Discovery of New Potency-Enhancing Interactions
  作者：Jamison B. Tuttle、Marie Anderson、Bruce M. Bechle、Brian M. Campbell、Cheng Chang、Amy B. Dounay、Edelweiss Evrard、Kari R. Fonseca、Xinmin Gan、Somraj Ghosh、Weldon Horner、Larry C. James、Ji-Young Kim、Laura A. McAllister、Jayvardhan Pandit、Vinod D. Parikh、Brian J. Rago、Michelle A. Salafia、Christine A. Strick、Laura E. Zawadzke、Patrick R. Verhoest

  DOI：10.1021/ml300237v

  日期：2013.1.10

  A series of aryl hydroxamates recently have been disclosed as irreversible inhibitors of kynurenine amino transferase II (KAT II), an enzyme that may play a role in schizophrenia and other psychiatric and neurological disorders. The utilization of structure activity relationships (SAR) in conjunction with X-ray crystallography led to the discovery of hydroxamate 4, a disubstituted analogue that has a significant potency enhancement due to a novel interaction with KAT II. The use of k(inact)/K-i to assess potency was critical for understanding the SAR in this series and for identifying compounds with improved pharmacodynamic profiles.