(1E,4E)-1-(4-aminophenyl)-5-(4-bromophenyl)penta-1,4-dien-3-one | 1285534-38-4

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 肉桂酸及其衍生物
• 英文名称: (1E,4E)-1-(4-aminophenyl)-5-(4-bromophenyl)penta-1,4-dien-3-one
• CAS: 1285534-38-4
• 化学式: C₁₇H₁₄BrNO
• 分子量: 328.208
• InChiKey: CEXATJAZTLESNF-YDWXAUTNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  43.1
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (1E,4E)-1-(4-aminophenyl)-5-(4-bromophenyl)penta-1,4-dien-3-one 在 四(三苯基膦)钯 、 三正丁基氢锡 、 盐酸 、 sodium iodide 、 双氧水 作用下， 以 甲苯 、 水 为溶剂， 反应 10.0h， 生成 C₁₇H₁₄⁽¹²⁵⁾INO
  参考文献：
  名称：

  Synthesis and Structure−Affinity Relationships of Novel Dibenzylideneacetone Derivatives as Probes for β-Amyloid Plaques

  摘要：

  A new and extensive set of dibenzylideneacetone derivatives was synthesized and screened for affinity toward A beta(1-42) aggregates. Structure-activity relationships revealed the binding of dibenzylideneacetones to be affected by various substituents. The introduction of a substituent group in the ortho position reduced or abolished the binding. However, the para position was highly tolerant of sterically demanding substitutions. Three radioiodinated ligands (6, 70, and 71) and two F-18 fluoro-pegylated (FPEG) ligands (83 and 85) were prepared, all of which displayed high affinity folr A beta(1-42) aggregates (K-i ranging from 0.9 to 7.0 nM). In biodistribution experiments, they exhibited good initial penetration (1.59, 4.68, 4.56, 4.13, and 5.15% ID/g, respectively, at 2 min) of and fast clearance from the brain. Autoradiography with sections of postmortem AD brain and transgenic mouse brain confirmed the high affinity of these tracers. These preliminary results strongly suggest the dibenzylideneacetone structure to be a potential new scaffold for beta-amyloid imaging probes.

  DOI：

  10.1021/jm101404k
• 作为产物：
  描述：

  对硝基苄叉丙酮 在 盐酸 、 sodium methylate 、 tin(ll) chloride 作用下， 以 甲醇 、 乙醇 、 水 为溶剂， 反应 14.0h， 生成 (1E,4E)-1-(4-aminophenyl)-5-(4-bromophenyl)penta-1,4-dien-3-one
  参考文献：
  名称：

  Synthesis and Structure−Affinity Relationships of Novel Dibenzylideneacetone Derivatives as Probes for β-Amyloid Plaques

  摘要：

  A new and extensive set of dibenzylideneacetone derivatives was synthesized and screened for affinity toward A beta(1-42) aggregates. Structure-activity relationships revealed the binding of dibenzylideneacetones to be affected by various substituents. The introduction of a substituent group in the ortho position reduced or abolished the binding. However, the para position was highly tolerant of sterically demanding substitutions. Three radioiodinated ligands (6, 70, and 71) and two F-18 fluoro-pegylated (FPEG) ligands (83 and 85) were prepared, all of which displayed high affinity folr A beta(1-42) aggregates (K-i ranging from 0.9 to 7.0 nM). In biodistribution experiments, they exhibited good initial penetration (1.59, 4.68, 4.56, 4.13, and 5.15% ID/g, respectively, at 2 min) of and fast clearance from the brain. Autoradiography with sections of postmortem AD brain and transgenic mouse brain confirmed the high affinity of these tracers. These preliminary results strongly suggest the dibenzylideneacetone structure to be a potential new scaffold for beta-amyloid imaging probes.

  DOI：

  10.1021/jm101404k

文献信息

• Design, Synthesis and Biological Evaluation of Hybrid Molecules Containing Conjugated Styryl Ketone and α-Bromoacryloyl Moieties
  作者：Romeo Romagnoli、Pier Giovanni Baraldi、Olga Cruz-Lopez、Maria Kimatrai Salvador、Delia Preti、Mojgan Aghazadeh Tabrizi、Jan Balzarini、Alessandro Canella、Enrica Fabbri、Roberto Gambari

  DOI：10.2174/157018012799079842

  日期：2012.2.1

  There was a major interest in the last years in the design of anticancer agents containing the 1,5-diaryl-3-oxo- 1,4-pentadienyl system. The modification of this pharmacophore by the introduction of an additional Michael acceptor represents a strategy to obtain novel potential antiproliferative agents. In a continuing study of hybrid compounds containing the α-bromoacryloyl moiety as potential anticancer drugs, we synthesized two novel series of hybrids 3a-i and 4a-i, in which this moiety was linked to the 1,5-diaryl-1,4-pentadien-3-one system. Many of the conjugates prepared (3b, 3c and 3g) demonstrated pronounced antiproliferative activity against five cancer cell lines, being more active than the reference compound Melphalan. Compounds 3e and 4b were also examined for their effects on the cell cycle progression of K562 cells. The detection of a sub-G1 peak upon incubation with these compounds suggested that 3e and 4b also exert their growth inhibiting effects by induction of apoptosis.

  近年来，人们对设计含有 1,5-二芳基-3-氧代-1,4-戊二烯体系的抗癌剂产生了浓厚的兴趣。通过引入额外的迈克尔受体对这一药理体系进行修饰，是获得新型潜在抗增殖药物的一种策略。在继续研究含有 α-溴丙烯酰基的杂化化合物作为潜在抗癌药物的过程中，我们合成了两个新系列的杂化化合物 3a-i 和 4a-i，其中该基团与 1,5-二芳基-1,4-戊二烯-3-酮体系相连。所制备的许多共轭物（3b、3c 和 3g）对五种癌细胞株具有明显的抗增殖活性，其活性高于参考化合物美法仑。还研究了化合物 3e 和 4b 对 K562 细胞周期进展的影响。在与这两种化合物一起孵育时检测到了亚 G1 峰，这表明 3e 和 4b 还通过诱导细胞凋亡来发挥其抑制生长的作用。
• Synthesis and Structure−Affinity Relationships of Novel Dibenzylideneacetone Derivatives as Probes for β-Amyloid Plaques
  作者：Mengchao Cui、Masahiro Ono、Hiroyuki Kimura、Boli Liu、Hideo Saji

  DOI：10.1021/jm101404k

  日期：2011.4.14

  A new and extensive set of dibenzylideneacetone derivatives was synthesized and screened for affinity toward A beta(1-42) aggregates. Structure-activity relationships revealed the binding of dibenzylideneacetones to be affected by various substituents. The introduction of a substituent group in the ortho position reduced or abolished the binding. However, the para position was highly tolerant of sterically demanding substitutions. Three radioiodinated ligands (6, 70, and 71) and two F-18 fluoro-pegylated (FPEG) ligands (83 and 85) were prepared, all of which displayed high affinity folr A beta(1-42) aggregates (K-i ranging from 0.9 to 7.0 nM). In biodistribution experiments, they exhibited good initial penetration (1.59, 4.68, 4.56, 4.13, and 5.15% ID/g, respectively, at 2 min) of and fast clearance from the brain. Autoradiography with sections of postmortem AD brain and transgenic mouse brain confirmed the high affinity of these tracers. These preliminary results strongly suggest the dibenzylideneacetone structure to be a potential new scaffold for beta-amyloid imaging probes.