3-(N-methylmethylsulfonamido)-N,N-dipropyl-5-(ethynyl)benzamide | 1314806-88-6

• 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: 3-(N-methylmethylsulfonamido)-N,N-dipropyl-5-(ethynyl)benzamide
• CAS: 1314806-88-6
• 化学式: C₁₇H₂₄N₂O₃S
• 分子量: 336.455
• InChiKey: BESHMDKTIDUPGY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.33
• 重原子数：
  23.0
• 可旋转键数：
  7.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  57.69
• 氢给体数：
  0.0
• 氢受体数：
  3.0

反应信息

• 作为产物：
  描述：

  3-bromo-5-(N-methylmethylsulfonamido)benzoic acid 在 bis-triphenylphosphine-palladium(II) chloride 、 copper(l) iodide 、 四丁基氟化铵 、 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 18.0h， 生成 3-(N-methylmethylsulfonamido)-N,N-dipropyl-5-(ethynyl)benzamide
  参考文献：
  名称：

  Triazole-linked reduced amide isosteres: An approach for the fragment-based drug discovery of anti-Alzheimer’s BACE1 inhibitors

  摘要：

  In the course of a beta-site APP-cleaving enzyme 1 (BACE1) inhibitor discovery project an in situ synthesis/screening protocol was employed to prepare 120 triazole-linked reduced amide isostere inhibitors. Among these compounds, four showed modest (single digit micromolar) BACE1 inhibition. Our ligand design was based on a potent reduced amide isostere 1, wherein the P(2) amide moiety was replaced with an anti-1,2,3-triazole unit. Unfortunately, this replacement resulted in a 1000-fold decrease in potency. Docking studies of triazole-linked reduced amide isostere A3Z10 and potent oxadiazole-linked tertiary carbinamine 2a with BACE1 suggests that the docking poses of A3Z10 and 2a in the active sites are quite similar, with one exception. In the docked structures the placement of the protonated amine that engages D228 differs considerably between 2a and A3Z10. This difference could account for the lower BACE1 inhibition potency of A3Z10 and related compounds relative to 2a. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.05.007