6-(3-bromophenyl)-1-(4-methoxybenzylamino)-3,6-dimethyl-5,6-dihydro-3H-pyrimidin-4-one

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 6-(3-bromophenyl)-1-(4-methoxybenzylamino)-3,6-dimethyl-5,6-dihydro-3H-pyrimidin-4-one
• 英文别名: 6-(3-bromo-phenyl)-2-imino-1-(4-methoxy-benzyl)-3,6-dimethyl-tetrahydro-1H-pyrimidin-4-one；6-(3-bromo-phenyl)-1-(4-methoxy-benzylamino)-3,6-dimethyl-5,6-dihydro-3H-pyrimidin-4-one；6-(3-bromophenyl)-2-imino-1-(4-methoxybenzyl)-3,6-dimethyltetrahydropyrimidin-4(1H)-one；6-(3-bromophenyl)-2-imino-1-[(4-methoxyphenyl)methyl]-3,6-dimethyl-1,3-diazinan-4-one
• 化学式: C₂₀H₂₂BrN₃O₂
• 分子量: 416.318
• InChiKey: PCIKJGQMTKYUTG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  26
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  56.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  6-(3-bromophenyl)-1-(4-methoxybenzylamino)-3,6-dimethyl-5,6-dihydro-3H-pyrimidin-4-one 在 ammonium cerium(IV) nitrate 、 碳酸氢钠 作用下， 以 乙腈 为溶剂， 反应 20.0h， 以79%的产率得到2-amino-6-(3-bromophenyl)-3,6-dimethyl-5,6-dihydro-3H-pyrimidin-4-one
  参考文献：
  名称：

  [EN] SUBSTITUTED AMINO-PYRIMIDONES AND USES THEREOF
  [FR] AMINO-PYRIMIDONES SUBSTITUES ET UTILISATION DE CEUX-CI

  摘要：

  这项发明涉及具有下面的结构式Ia或结构式Ib的新化合物：(Ia, Ib)，以及它们的药学上可接受的盐、互变异构体或体内水解前体，以及它们的组合物和使用方法。这些新化合物提供了治疗或预防与Aß相关的病理学，如认知障碍、阿尔茨海默病、神经退行性疾病和痴呆症。

  公开号：

  WO2006041405A1
• 作为产物：
  描述：

  (E)-3-(3-bromo-phenyl)-N-cyano-N-methyl-but-2-enamide 、 4-甲氧基苄胺 在 crude compound 、 二氯甲烷 、 甲醇 、 methanol-dichloromethane 、 crude product 、 乙醚 、 乙酸乙酯 、 甲醇乙酸乙酯 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 以to give 15.48 gram (81% yield) of the title compound的产率得到6-(3-bromophenyl)-1-(4-methoxybenzylamino)-3,6-dimethyl-5,6-dihydro-3H-pyrimidin-4-one
  参考文献：
  名称：

  2-Aminopyrimidin-4-Ones And Their Use For Treating Or Preventing Alpha Beta-Related Pathologies

  摘要：

  本发明涉及具有以下结构式(I)的新化合物：[化学式应插入此处。请参见纸质副本]以及它们的药学上可接受的盐、组合物和使用方法。这些新化合物提供了治疗或预防认知障碍、阿尔茨海默病、神经退行性疾病和痴呆症的方法。

  公开号：

  US20090099217A1

文献信息

• [EN] SUBSTITUTED AMINO-COMPOUNDS AND USES THEREOF<br/>[FR] COMPOSES AMINO SUBSTITUES ET UTILISATION DE CES COMPOSE
  申请人：ASTRAZENECA AB

  公开号：WO2006041404A1

  公开（公告）日：2006-04-20

  This invention relates to novel compounds having the structural formula Ia or formula Ib: Ia Ib and their pharmaceutically acceptable salts, tautomers or in vivo hydrolysable precursors, compositions and methods of use thereof. These novel compounds provide a treatment or prophylaxis of Aβ related pathologies such as cognitive impairment, Alzheimer Disease, neurodegeneration and dementia.

  这项发明涉及具有结构式Ia或结构式Ib的新化合物：Ia Ib及其药用可接受的盐、互变异构体或体内可水解的前体，以及其组合物和使用方法。这些新化合物提供了治疗或预防与Aβ相关的病理学，如认知障碍、阿尔茨海默病、神经退行性疾病和痴呆症的方法。
• Substituted 2-Aminopyrimidine-4-Ones, Their Pharmaceutical Compositions And Their Use In The Treatment And/Or Prevention Of Ab-Related Pathologies
  申请人：Berg Stefan

  公开号：US20090023762A1

  公开（公告）日：2009-01-22

  This invention relates to novel compounds having the structural formula (I) below: and to their pharmaceutically acceptable salt, compositions and methods of use. These novel en compounds provide a treatment or prophylaxis of cognitive impairment, Alzheimer Disease, neurodegeneration and dementia.

  本发明涉及具有下列结构式（I）的新化合物，以及它们的药学上可接受的盐、组合物和使用方法。这些新的化合物提供了治疗或预防认知障碍、阿尔茨海默病、神经退行性疾病和痴呆症的方法。
• Substituted Amino-Compounds and Uses Thereof
  申请人：Albert Jeffrey Scott

  公开号：US20090221579A1

  公开（公告）日：2009-09-03

  This invention relates to novel compounds having the structural formula Ia or formula Ib: Ia Ib and their pharmaceutically acceptable salts, tautomers or in vivo hydrolysable precursors, compositions and methods of use thereof. These novel compounds provide a treatment or prophylaxis of Aβ related pathologies such as cognitive impairment, Alzheimer Disease, neurodegeneration and dementia.

  本发明涉及具有结构式Ia或式Ib的新化合物：Ia Ib及其药学上可接受的盐、互变异构体或体内水解前体，以及其使用的组合物和方法。这些新化合物提供了治疗或预防与Aβ相关的病理学，如认知障碍、阿尔茨海默病、神经退行性和痴呆症的方法。
• Substituted Amino-Pyrimidones and Uses Thereof
  申请人：Albert Jeffrey Scott

  公开号：US20090062282A1

  公开（公告）日：2009-03-05

  This invention relates to novel compounds having the structural formula Ia or formula Ib below: (Ia, Ib), and their pharmaceutically acceptable salts, tautomers or in vivo hydrolysable precursors, compositions and methods of use thereof. These novel compounds provide a treatment or prophylaxis of Aβ related pathologies such as cognitive impairment, Alzheimer Disease, neurodegeneration and dementia.

  本发明涉及具有下列结构式Ia或结构式Ib的新化合物：（Ia，Ib），以及它们的药学上可接受的盐，互变异构体或体内水解前体，以及它们的组合物和使用方法。这些新化合物可用于治疗或预防与Aβ相关的病理学，如认知障碍，阿尔茨海默病，神经退行性和痴呆症。
• Application of Fragment-Based Lead Generation to the Discovery of Novel, Cyclic Amidine β-Secretase Inhibitors with Nanomolar Potency, Cellular Activity, and High Ligand Efficiency
  作者：Philip D. Edwards、Jeffrey S. Albert、Mark Sylvester、David Aharony、Donald Andisik、Owen Callaghan、James B. Campbell、Robin A. Carr、Gianni Chessari、Miles Congreve、Martyn Frederickson、Rutger H. A. Folmer、Stefan Geschwindner、Gerard Koether、Karin Kolmodin、Jennifer Krumrine、Russell C. Mauger、Christopher W. Murray、Lise-Lotte Olsson、Sahil Patel、Nate Spear、Gaochao Tian

  DOI：10.1021/jm070829p

  日期：2007.11.1

  Fragment-based lead generation has led to the discovery of a novel series of cyclic amidine-based inhibitors of beta-secretase (BACE-1). Initial fragment hits with an isocytosine core having millimolar potency were identified via NMR affinity screening. Structure-guided evolution of these fragments using X-ray crystallography together with potency determination using surface plasmon resonance and functional enzyme inhibition assays afforded micromolar inhibitors. Similarity searching around the isocytosine core led to the identification of a related series of inhibitors, the dihydroisocytosines. By leveraging the knowledge of the ligand-BACE-1 recognition features generated from the isocytosines, the dihydroisocytosines were efficiently optimized to submicromolar potency. Compound 29, with an IC50 of 80 nM, a ligand efficiency of 0.37, and cellular activity of 470 nM, emerged as the lead structure for future optimization.