(Z)-3-(4-(4-methylpiperazin-1-yl)phenyl)-2-phenylacrylonitrile | 1361503-89-0

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 二苯乙烯类
• 英文名称: (Z)-3-(4-(4-methylpiperazin-1-yl)phenyl)-2-phenylacrylonitrile
• 英文别名: (Z)-3-[4-(4-methylpiperazin-1-yl)phenyl]-2-phenylprop-2-enenitrile
• CAS: 1361503-89-0
• 化学式: C₂₀H₂₁N₃
• 分子量: 303.407
• InChiKey: NORAHHUELCHSJN-XDJHFCHBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  23
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  30.3
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  N-甲基哌嗪 在 四氢吡咯 、 potassium carbonate 作用下， 以 甲醇 、 二甲基亚砜 为溶剂， 生成 (Z)-3-(4-(4-methylpiperazin-1-yl)phenyl)-2-phenylacrylonitrile
  参考文献：
  名称：

  (Z)-2-(2-Bromophenyl)-3-{[4-(1-methyl-piperazine)amino]phenyl}acrylonitrile (DG172): An Orally Bioavailable PPARβ/δ-Selective Ligand with Inverse Agonistic Properties

  摘要：

  The ligand-regulated nuclear receptor peroxisome proliferator-activated receptor beta/delta (PPAR beta/delta) is a potential pharmacological target due to its role in disease-related biological processes. We used TR-FRET-based competitive ligand binding and coregulator interaction assays to screen 2693 compounds of the Open Chemical Repository of the NCl/NIH Developmental Therapeutics Program for inhibitory PPAR beta/delta ligands. One compound, (Z)-3-(4-dimethylamino-phenyl)-2-phenyl-acrylonitrile, was used for a systematic SAR study. This led to the design of derivative 37, (Z)-2-(2-bromopheny1)-3-{[4-(1-methyl-piperazine)amino]phenyl}acrylonitrile (DG172), a novel PPAR beta/delta-selective ligand showing high binding affinity (IC50 = 27 nM) and potent inverse agonistic properties. 37 selectively inhibited the agonist-induced activity of PPAR beta/delta, enhanced transcriptional corepressor recruitment, and down-regulated transcription of the PPAR beta/delta target gene Angptl4 in mouse myoblasts (IC50 = 9.5 nM). Importantly, 37 was bioavailable after oral application to mice with peak plasma levels in the concentration range of its maximal inhibitory potency, suggesting that 37 will be an invaluable tool to elucidate the functions and therapeutic potential of PPAR beta/delta.

  DOI：

  10.1021/jm2017122

文献信息

• [DE] STILBEN-VERBINDUNGEN ALS PPAR BETA/DELTA INHIBITOREN FÜR DIE BEHANDLUNG VON PPAR BETA/DELTA-VERMITTELTEN ERKRANKUNGEN<br/>[EN] STILBENE COMPOUNDS AS PPAR BETA/DELTA INHIBITORS FOR TREATING PPAR BETA/DELTA TRANSMITTED ILLNESSES<br/>[FR] COMPOSÉS DE STILBÈNE EN TANT QU'INHIBITEURS DE PPAR BÊTA/DELTA POUR LE TRAITEMENT DE MALADIES MÉDIÉES PAR LES PPRAR BÊTA/DELTA
  申请人：UNIV MARBURG PHILIPPS

  公开号：WO2013072390A2

  公开（公告）日：2013-05-23

  Die vorliegende Erfindung betrifft Substanzen, die als selektive Liganden von nukleären Rezeptoren des PPAR beta/delta-Subtyps wirken und für die Behandlung von PPAR beta/delta-vermittelten Erkrankungen verwendet werden können. Die erfindungsgemäßen Substanzen wirken als Inhibitoren des PPAR beta/delta Rezeptors.
• (<i>Z</i>)-2-(2-Bromophenyl)-3-{[4-(1-methyl-piperazine)amino]phenyl}acrylonitrile (DG172): An Orally Bioavailable PPARβ/δ-Selective Ligand with Inverse Agonistic Properties
  作者：Sonja Lieber、Frithjof Scheer、Wolfgang Meissner、Simone Naruhn、Till Adhikary、Sabine Müller-Brüsselbach、Wibke E. Diederich、Rolf Müller

  DOI：10.1021/jm2017122

  日期：2012.3.22

  The ligand-regulated nuclear receptor peroxisome proliferator-activated receptor beta/delta (PPAR beta/delta) is a potential pharmacological target due to its role in disease-related biological processes. We used TR-FRET-based competitive ligand binding and coregulator interaction assays to screen 2693 compounds of the Open Chemical Repository of the NCl/NIH Developmental Therapeutics Program for inhibitory PPAR beta/delta ligands. One compound, (Z)-3-(4-dimethylamino-phenyl)-2-phenyl-acrylonitrile, was used for a systematic SAR study. This led to the design of derivative 37, (Z)-2-(2-bromopheny1)-3-[4-(1-methyl-piperazine)amino]phenyl}acrylonitrile (DG172), a novel PPAR beta/delta-selective ligand showing high binding affinity (IC50 = 27 nM) and potent inverse agonistic properties. 37 selectively inhibited the agonist-induced activity of PPAR beta/delta, enhanced transcriptional corepressor recruitment, and down-regulated transcription of the PPAR beta/delta target gene Angptl4 in mouse myoblasts (IC50 = 9.5 nM). Importantly, 37 was bioavailable after oral application to mice with peak plasma levels in the concentration range of its maximal inhibitory potency, suggesting that 37 will be an invaluable tool to elucidate the functions and therapeutic potential of PPAR beta/delta.