1-benzyl-5-bromo-2-methoxy-4-nitrobenzene | 1258545-41-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 1-benzyl-5-bromo-2-methoxy-4-nitrobenzene
• CAS: 1258545-41-3
• 化学式: C₁₄H₁₂BrNO₃
• 分子量: 322.158
• InChiKey: WUYBRIGBHUMFDU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  55
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-benzyl-5-bromo-2-methoxy-4-nitrobenzene 在 5%-palladium/activated carbon 、 甲酸铵 、 锌 作用下， 以 吡啶 、 N,N-二甲基甲酰胺 为溶剂， 反应 36.42h， 生成 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 作用下， 以 四氢呋喃 、 乙腈 为溶剂， 反应 18.17h， 生成 1-benzyl-5-bromo-2-methoxy-4-nitrobenzene
  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。
• [EN] TRICYCLIC COMPOUNDS AS KAT II INHIBITORS<br/>[FR] COMPOSÉS TRICYCLIQUES EN TANT QU'INHIBITEURS DE KAT II
  申请人：PFIZER

  公开号：WO2013186666A1

  公开（公告）日：2013-12-19

  Compounds of Formula (I), wherein R1, R 2, X1, Y1, Z1, and Z2 are as defined herein, and pharmaceutically acceptable salts thereof, are described as useful for the treatment of cognitive deficits associated with schizophrenia and other psychiatric, neurodegenerative and/or neurological disorders in mammals, including humans.

  该文描述了式(I)的化合物及其药学上可接受的盐，其中R1、R2、X1、Y1、Z1和Z2的定义如本文所述，可用于治疗哺乳动物，包括人类中与精神分裂症和其他精神、神经退行性和/或神经性疾病相关的认知缺陷。
• TRICYCLIC COMPOUNDS AS KAT II INHIBITORS
  申请人：PFIZER INC.

  公开号：US20150175603A1

  公开（公告）日：2015-06-25

  Compounds of Formula (I), wherein R 1 , R 2 , X 1 , Y 1 , Z 1 , and Z 2 are as defined herein, and pharmaceutically acceptable salts thereof, are described as useful for the treatment of cognitive deficits associated with schizophrenia and other psychiatric, neurodegenerative and/or neurological disorders in mammals, including humans.

  公式（I）的化合物，其中R1，R2，X1，Y1，Z1和Z2如此定义，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，患有精神分裂症和其他精神、神经退行性和/或神经系统疾病相关的认知缺陷的有用化合物。
• 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