6-(3-bromophenethyl)-1-(4-methoxybenzylamino)-tetrahydro-2-imino-3,6-dimethyl-pyrimidin-4(1H)-one | 951677-52-4

• 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-bromophenethyl)-1-(4-methoxybenzylamino)-tetrahydro-2-imino-3,6-dimethyl-pyrimidin-4(1H)-one
• 英文别名: 6-[2-(3-bromophenyl)ethyl]-2-imino-1-(4-methoxybenzyl)-3,6-dimethyltetrahydropyrimidin-4(1H)-one；6-[2-(3-bromophenyl)ethyl]-2-imino-1-[(4-methoxyphenyl)methyl]-3,6-dimethyl-1,3-diazinan-4-one
• CAS: 951677-52-4
• 化学式: C₂₂H₂₆BrN₃O₂
• 分子量: 444.371
• InChiKey: UDKJZLXTVZLNIH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  28
• 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：
  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-bromophenethyl)-1-(4-methoxybenzylamino)-tetrahydro-2-imino-3,6-dimethyl-pyrimidin-4(1H)-one 在 ammonium cerium(IV) nitrate 、 水 、 Celite 、 碳酸氢钠 作用下， 以 乙腈 、 水 为溶剂， 反应 19.0h， 以90%的产率得到6-(3-bromophenethyl)-2-amino-5,6-dihydro-3,6-dimethylpyrimidin-4(3H)-one
  参考文献：
  名称：

  WO2007/114771

  摘要：

  公开号：
• 作为产物：
  描述：

  (2E)-5-(3-bromophenyl)-N-cyano-N,3-dimethylpent-2-enamide 、 4-甲氧基苄胺 在 crude compound 、 silica gel 、 methanol-dichloromethane 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 以to give 20.45 g of the semi-pure title compound which的产率得到6-(3-bromophenethyl)-1-(4-methoxybenzylamino)-tetrahydro-2-imino-3,6-dimethyl-pyrimidin-4(1H)-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

• WO2007/114771
  申请人：——

  公开号：——

  公开（公告）日：——
• [EN] 2-AMINOPYRIMIDIN-4-ONES AND THEIR USE FOR TREATING OR PREVENTING Aß-RELATED PATHOLOGIES<br/>[FR] 2-AMINOPYRIMIDIN-4-ONES ET LEUR UTILISATION POUR LE TRAITEMENT OU LA PREVENTION DE PATHOLOGIES LIEES A LA PROTEINE Aß
  申请人：ASTRAZENECA AB

  公开号：WO2007114771A1

  公开（公告）日：2007-10-11

  [EN] This invention relates to novel compounds having the structural formula (I) below: [Chemical formula should be inserted here. Please see paper copy] and to their pharmaceutically acceptable salt, compositions and methods of use. These novel compounds provide a treatment or prophylaxis of cognitive impairment, Alzheimer Disease, neurodegeneration and dementia.
  [FR] La présente invention concerne de nouveaux composés de formule structurale (I) : [Insérer ici la formule chimique. Cf. document papier] et leur sel pharmaceutiquement acceptable, ainsi que leurs compositions et leurs procédés d'utilisation. Ces nouveaux composés permettent d'assurer le traitement ou la prophylaxie de troubles cognitifs, de la maladie d'Alzheimer, de la neurodégénérescence et de la démence.
• 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.
• 2-Aminopyrimidin-4-Ones And Their Use For Treating Or Preventing Alpha Beta-Related Pathologies
  申请人：Berg Stefan

  公开号：US20090099217A1

  公开（公告）日：2009-04-16

  This invention relates to novel compounds having the structural formula (I) below: [Chemical formula should be inserted here. Please see paper copy] and to their pharmaceutically acceptable salt, compositions and methods of use. These novel compounds provide a treatment or prophylaxis of cognitive impairment, Alzheimer Disease, neurodegeneration and dementia.

  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。