tert-butyl [(3S)-6-benzyl-1-hydroxy-7-methoxy-2-oxo-1,2,3,4-tetrahydroquinolin-3-yl]carbamate | 1258545-45-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: tert-butyl [(3S)-6-benzyl-1-hydroxy-7-methoxy-2-oxo-1,2,3,4-tetrahydroquinolin-3-yl]carbamate
• 英文别名: tert-butyl N-[(3S)-6-benzyl-1-hydroxy-7-methoxy-2-oxo-3,4-dihydroquinolin-3-yl]carbamate
• CAS: 1258545-45-7
• 化学式: C₂₂H₂₆N₂O₅
• 分子量: 398.459
• InChiKey: WAEFLRDLPPCATK-KRWDZBQOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  29
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  88.1
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  tert-butyl [(3S)-6-benzyl-1-hydroxy-7-methoxy-2-oxo-1,2,3,4-tetrahydroquinolin-3-yl]carbamate 在 盐酸 作用下， 以 甲醇 、 乙醚 、 二氯甲烷 为溶剂， 反应 1.08h， 以85%的产率得到(3S)-3-amino-6-benzyl-1-hydroxy-7-methoxy-3,4-dihydroquinolin-2(1H)-one hydrochloride
  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 、 5%-palladium/activated carbon 、 甲酸铵 、 palladium diacetate 、 copper(ll) bromide 、 锌 作用下， 以 四氢呋喃 、 吡啶 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 54.59h， 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

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。
• 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.