N-[3-[1-(4-bromo-thiophen-2-yl)-cyclohexylamino]-1-(3,5-difluoro-benzyl)-2-hydroxy-propyl]-acetamide | 861859-62-3

• 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: N-[3-[1-(4-bromo-thiophen-2-yl)-cyclohexylamino]-1-(3,5-difluoro-benzyl)-2-hydroxy-propyl]-acetamide
• 英文别名: N-[(2S,3R)-4-[[1-(4-bromothiophen-2-yl)cyclohexyl]amino]-1-(3,5-difluorophenyl)-3-hydroxybutan-2-yl]acetamide
• CAS: 861859-62-3
• 化学式: C₂₂H₂₇BrF₂N₂O₂S
• 分子量: 501.435
• InChiKey: CZAXGWBBJNUJRB-VQTJNVASSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  30
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  89.6
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  N-[3-[1-(4-bromo-thiophen-2-yl)-cyclohexylamino]-1-(3,5-difluoro-benzyl)-2-hydroxy-propyl]-acetamide 、 三丁基(1-丙烯-2-基)锡 在 四(三苯基膦)钯 作用下， 以 DMF (N,N-dimethyl-formamide) 为溶剂， 反应 18.0h， 生成 N-{1-(3,5-difluoro-benzyl)-2-hydroxy-3-[1-(4-isopropenyl-thiophen-2-yl)-cyclohexylamino]-propyl}-acetamide
  参考文献：
  名称：

  [EN] SUBSTITUTED UREA AND CARBAMATE, PHENACYL-2-HYDROXY-3-DIAMINOALKANE, AND BENZAMIDE-2-HYDROXY-3-DIAMINOALKANE ASPARTYL-PROTEASE INHIBITORS
  [FR] UREE ET CARBAMATE SUBSTITUES, PHENACYL-2-HYDROXY-3-DIAMINOALCANE, ET BENZAMIDE-2-HYDROXY-3-DIAMINOALCANE INHIBITEURS D'ASPARTYL-PROTEASE

  摘要：

  这项发明涉及乙酰2-羟基-1,3-二氨基螺环己烷及其衍生物，可用于治疗与淀粉样变性相关的至少一种疾病、紊乱和病况。淀粉样变性指与A-beta蛋白异常沉积相关的一系列疾病、紊乱和病况。

  公开号：

  WO2005087215A1
• 作为产物：
  描述：

  3-amino-1-[1-(4-bromo-thiophen-2-yl)-cyclohexylamino]-4-(3,5-difluoro-phenyl)-butan-2-ol 、 N-甲氧基二乙酰胺 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 18.0h， 生成 N-[3-[1-(4-bromo-thiophen-2-yl)-cyclohexylamino]-1-(3,5-difluoro-benzyl)-2-hydroxy-propyl]-acetamide
  参考文献：
  名称：

  Design and synthesis of hydroxyethylamine (HEA) BACE-1 inhibitors: Structure–activity relationship of the aryl region

  摘要：

  The structure-activity relationship of the prime region of hydroxyethylamine BACE inhibitors is described. Variation in the aryl linker region with 5- and 6-membered heterocycles provided compounds such as 33 with improved permeability and reduced P-gp liability compared to benzyl amine analog 1. (c) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.08.070

文献信息

• [EN] METHODS OF TREATMENT OF AMYLOIDOSIS USING ASPARTYL-PROTEASE INIHIBITORS<br/>[FR] PROCEDES DE TRAITEMENT D'AMYLOIDOSE UTILISANT DES INHIBITEURS DE PROTEASE ASPARTYLE
  申请人：ELAN PHARM INC

  公开号：WO2005070407A1

  公开（公告）日：2005-08-04

  The invention relates to acetyl 2-hydroxy-1,3-diaminospirocyclohexanes and derivatives thereof that are useful in treating diseases, disorders, and conditions associated with amyloidosis. Amyloidosis refers to a collection of diseases, disorders, and conditions associated with abnormal deposition of A-beta protein.

  这项发明涉及乙酰2-羟基-1,3-二氨基螺环己烷及其衍生物，可用于治疗与淀粉样变性相关的疾病、疾病和症状。淀粉样变性是指与A-beta蛋白异常沉积相关的一系列疾病、疾病和症状。
• [EN] SUBSTITUTED UREA AND CARBAMATE, PHENACYL-2-HYDROXY-3-DIAMINOALKANE, AND BENZAMIDE-2-HYDROXY-3-DIAMINOALKANE ASPARTYL-PROTEASE INHIBITORS<br/>[FR] UREE ET CARBAMATE SUBSTITUES, PHENACYL-2-HYDROXY-3-DIAMINOALCANE, ET BENZAMIDE-2-HYDROXY-3-DIAMINOALCANE INHIBITEURS D'ASPARTYL-PROTEASE
  申请人：ELAN PHARM INC

  公开号：WO2005087215A1

  公开（公告）日：2005-09-22

  The invention relates to acetyl 2-hydroxy-1,3-diaminospirocyclohexanes and derivatives thereof that are useful in treating at least one disease, disorder, and condition associated with amyloidosis. Amyloidosis refers to a collection of diseases, disorders, and condition associated with abnormal deposition of A-beta protein.

  这项发明涉及乙酰2-羟基-1,3-二氨基螺环己烷及其衍生物，可用于治疗与淀粉样变性相关的至少一种疾病、紊乱和病况。淀粉样变性指与A-beta蛋白异常沉积相关的一系列疾病、紊乱和病况。
• Design and synthesis of hydroxyethylamine (HEA) BACE-1 inhibitors: Structure–activity relationship of the aryl region
  作者：Gary D. Probst、Simeon Bowers、Jennifer M. Sealy、Brian Stupi、Darren Dressen、Barbara M. Jagodzinska、Jose Aquino、Andrea Gailunas、Anh P. Truong、Luke Tso、Ying-Zi Xu、Roy K. Hom、Varghese John、Jay S. Tung、Michael A. Pleiss、John A. Tucker、Andrei W. Konradi、Hing L. Sham、Jacek Jagodzinski、Gergely Toth、Eric Brecht、Nanhua Yao、Hu Pan、May Lin、Dean R. Artis、Lany Ruslim、Michael P. Bova、Sukanto Sinha、Ted A. Yednock、Shawn Gauby、Wes Zmolek、Kevin P. Quinn、John-Michael Sauer

  DOI：10.1016/j.bmcl.2010.08.070

  日期：2010.10

  The structure-activity relationship of the prime region of hydroxyethylamine BACE inhibitors is described. Variation in the aryl linker region with 5- and 6-membered heterocycles provided compounds such as 33 with improved permeability and reduced P-gp liability compared to benzyl amine analog 1. (c) 2010 Elsevier Ltd. All rights reserved.