1-(3-Bromophenyl)-2-[1-(2-trimethylsilylethoxymethyl)pyrazol-4-yl]ethane-1,2-dione | 918487-24-8

• 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: 1-(3-Bromophenyl)-2-[1-(2-trimethylsilylethoxymethyl)pyrazol-4-yl]ethane-1,2-dione
• CAS: 918487-24-8
• 化学式: C₁₇H₂₁BrN₂O₃Si
• 分子量: 409.355
• InChiKey: LQALUNZYRBDCOL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.02
• 重原子数：
  24
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  61.2
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-(3-Bromophenyl)-2-[1-(2-trimethylsilylethoxymethyl)pyrazol-4-yl]ethane-1,2-dione 在 盐酸 、 四(三苯基膦)钯 、 水 、 sodium hydride 、 sodium carbonate 作用下， 以 1,4-二氧六环 、 甲醇 、 乙醇 、 水 为溶剂， 生成 2-Amino-5-[3-(2-fluoropyridin-3-yl)phenyl]-5-(1-isobutyl-1H-pyrazol-4-yl)-3-methyl-3,5-dihydro-4H-imidazol-4-one
  参考文献：
  名称：

  New pyrazolyl and thienyl aminohydantoins as potent BACE1 inhibitors: Exploring the S2′ region

  摘要：

  The proteolytic enzyme beta-secretase (BACE1) plays a central role in the synthesis of the pathogenic beta-amyloid in Alzheimer's disease. SAR studies of the S2' region of the BACE1 ligand binding pocket with pyrazolyl and thienyl P2' side chains are reported. These analogs exhibit low nanomolar potency for BACE1, and demonstrate >50-to 100-fold selectivity for the structurally related aspartyl proteases BACE2 and cathepsin D. Small groups attached at the nitrogen of the P2' pyrazolyl moiety, together with the P3 pyrimidine nucleus projecting into the S3 region of the binding pocket, are critical components to ligand's potency and selectivity. P2' thiophene side chain analogs are highly potent BACE1 inhibitors with excellent selectivity against cathepsin D, but only modest selectivity against BACE2. The cell-based activity of these new analogs tracked well with their increased molecular binding with EC50 values of 0.07-0.2 mu M in the ELISA assay for the most potent analogs. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.07.057
• 作为产物：
  描述：

  2-[[4-[2-(3-Bromophenyl)ethynyl]pyrazol-1-yl]methoxy]ethyl-trimethylsilane 在 potassium permanganate 、 水 、 碳酸氢钠 、 magnesium sulfate 作用下， 以 丙酮 为溶剂， 生成 1-(3-Bromophenyl)-2-[1-(2-trimethylsilylethoxymethyl)pyrazol-4-yl]ethane-1,2-dione
  参考文献：
  名称：

  New pyrazolyl and thienyl aminohydantoins as potent BACE1 inhibitors: Exploring the S2′ region

  摘要：

  The proteolytic enzyme beta-secretase (BACE1) plays a central role in the synthesis of the pathogenic beta-amyloid in Alzheimer's disease. SAR studies of the S2' region of the BACE1 ligand binding pocket with pyrazolyl and thienyl P2' side chains are reported. These analogs exhibit low nanomolar potency for BACE1, and demonstrate >50-to 100-fold selectivity for the structurally related aspartyl proteases BACE2 and cathepsin D. Small groups attached at the nitrogen of the P2' pyrazolyl moiety, together with the P3 pyrimidine nucleus projecting into the S3 region of the binding pocket, are critical components to ligand's potency and selectivity. P2' thiophene side chain analogs are highly potent BACE1 inhibitors with excellent selectivity against cathepsin D, but only modest selectivity against BACE2. The cell-based activity of these new analogs tracked well with their increased molecular binding with EC50 values of 0.07-0.2 mu M in the ELISA assay for the most potent analogs. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.07.057

文献信息

• New pyrazolyl and thienyl aminohydantoins as potent BACE1 inhibitors: Exploring the S2′ region
  作者：Michael S. Malamas、Jim Erdei、Iwan Gunawan、Keith Barnes、Yu Hui、Matthew Johnson、Albert Robichaud、Ping Zhou、Yinfa Yan、William Solvibile、Jim Turner、Kristi Yi Fan、Rajiv Chopra、Jonathan Bard、Menelas N. Pangalos

  DOI：10.1016/j.bmcl.2011.07.057

  日期：2011.9

  The proteolytic enzyme beta-secretase (BACE1) plays a central role in the synthesis of the pathogenic beta-amyloid in Alzheimer's disease. SAR studies of the S2' region of the BACE1 ligand binding pocket with pyrazolyl and thienyl P2' side chains are reported. These analogs exhibit low nanomolar potency for BACE1, and demonstrate >50-to 100-fold selectivity for the structurally related aspartyl proteases BACE2 and cathepsin D. Small groups attached at the nitrogen of the P2' pyrazolyl moiety, together with the P3 pyrimidine nucleus projecting into the S3 region of the binding pocket, are critical components to ligand's potency and selectivity. P2' thiophene side chain analogs are highly potent BACE1 inhibitors with excellent selectivity against cathepsin D, but only modest selectivity against BACE2. The cell-based activity of these new analogs tracked well with their increased molecular binding with EC50 values of 0.07-0.2 mu M in the ELISA assay for the most potent analogs. (C) 2011 Elsevier Ltd. All rights reserved.