methyl 3-benzyl-N-(tert-butoxycarbonyl)-O-methyl-6-nitro-L-tyrosinate | 1258545-43-5

• 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 3-benzyl-N-(tert-butoxycarbonyl)-O-methyl-6-nitro-L-tyrosinate
• 英文别名: methyl (2S)-3-(5-benzyl-4-methoxy-2-nitrophenyl)-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoate
• CAS: 1258545-43-5
• 化学式: C₂₃H₂₈N₂O₇
• 分子量: 444.485
• InChiKey: IOCVGLRMNLHGJT-SFHVURJKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  32
• 可旋转键数：
  10
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.39
• 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 3-benzyl-N-(tert-butoxycarbonyl)-O-methyl-6-nitro-L-tyrosinate 在 5%-palladium/activated carbon 、 甲酸铵 作用下， 以 吡啶 为溶剂， 反应 18.0h， 以27%的产率得到tert-butyl [(3S)-6-benzyl-1-hydroxy-7-methoxy-2-oxo-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：

  5-溴-4-甲氧基-2-硝基苯胺 在 SPhos 、 亚硝酸特丁酯 、 palladium diacetate 、 copper(ll) bromide 、 锌 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 36.59h， 生成 methyl 3-benzyl-N-(tert-butoxycarbonyl)-O-methyl-6-nitro-L-tyrosinate
  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：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