3-[5-(3-methoxybenzyl)-3-methyl-6-oxo-6H-pyridazin-1-yl]-propionic acid ethyl ester | 1184304-40-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 3-[5-(3-methoxybenzyl)-3-methyl-6-oxo-6H-pyridazin-1-yl]-propionic acid ethyl ester
• 英文别名: Ethyl 3-[5-[(3-methoxyphenyl)methyl]-3-methyl-6-oxopyridazin-1-yl]propanoate
• CAS: 1184304-40-2
• 化学式: C₁₈H₂₂N₂O₄
• 分子量: 330.384
• InChiKey: MMZNZCVFONNJMH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  24
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  68.2
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3-[5-(3-methoxybenzyl)-3-methyl-6-oxo-6H-pyridazin-1-yl]-propionic acid ethyl ester 在 sodium hydroxide 、 盐酸 作用下， 以 乙醇 、 水 为溶剂， 以96%的产率得到3-[5-[(3-Methoxyphenyl)methyl]-3-methyl-6-oxopyridazin-1-yl]propanoic acid
  参考文献：
  名称：

  6-Methyl-2,4-Disubstituted Pyridazin-3(2H)-ones: A Novel Class of Small-Molecule Agonists for Formyl Peptide Receptors

  摘要：

  Following a ligand-based drug design approach, a potent mixed formyl peptide receptor I (FPR1) and formyl peptide receptor-like I (FPRL1) agonist (14a) and a potent and specific FPRL1 agonist (14x) were identified. These compounds belong to a large series of pyridazin-3(2H)-one derivatives substituted with methyl group at position 6 and a methoxy benzyl at position 4. At position 2, an acetamide side chain is essential for activity. Likewise, the presence of lipophilic and/or electronegative substituents in the position para to the aryl group at the end of the chain plays a critical role for activity. Affinity for FPR1 receptors was evaluated by measuring intracellular calcium flux in HL-60 cells transfected with FPR1, FPRL1, and FPRL2, Agonists were able to activate intracellular calcium mobilization and chemotaxis in human neutrophils. The most potent chemotactic agent (EC50 = 0.6 mu M) was the mixed FPR/FPRL1 agonist 14h.

  DOI：

  10.1021/jm900592h
• 作为产物：
  描述：

  4-(3-methoxybenzyl)-6-methylpyridazin-3(2H)-one 、 alkaline earth salt of/the/ methylsulfuric acid 在 potassium carbonate 作用下， 以 乙腈 为溶剂， 反应 3.0h， 以86%的产率得到3-[5-(3-methoxybenzyl)-3-methyl-6-oxo-6H-pyridazin-1-yl]-propionic acid ethyl ester
  参考文献：
  名称：

  6-Methyl-2,4-Disubstituted Pyridazin-3(2H)-ones: A Novel Class of Small-Molecule Agonists for Formyl Peptide Receptors

  摘要：

  Following a ligand-based drug design approach, a potent mixed formyl peptide receptor I (FPR1) and formyl peptide receptor-like I (FPRL1) agonist (14a) and a potent and specific FPRL1 agonist (14x) were identified. These compounds belong to a large series of pyridazin-3(2H)-one derivatives substituted with methyl group at position 6 and a methoxy benzyl at position 4. At position 2, an acetamide side chain is essential for activity. Likewise, the presence of lipophilic and/or electronegative substituents in the position para to the aryl group at the end of the chain plays a critical role for activity. Affinity for FPR1 receptors was evaluated by measuring intracellular calcium flux in HL-60 cells transfected with FPR1, FPRL1, and FPRL2, Agonists were able to activate intracellular calcium mobilization and chemotaxis in human neutrophils. The most potent chemotactic agent (EC50 = 0.6 mu M) was the mixed FPR/FPRL1 agonist 14h.

  DOI：

  10.1021/jm900592h

文献信息

• 6-Methyl-2,4-Disubstituted Pyridazin-3(<i>2H</i>)-ones: A Novel Class of Small-Molecule Agonists for Formyl Peptide Receptors
  作者：Agostino Cilibrizzi、Mark T. Quinn、Liliya N. Kirpotina、Igor A. Schepetkin、Jeff Holderness、Richard D. Ye、Marie-Josephe Rabiet、Claudio Biancalani、Nicoletta Cesari、Alessia Graziano、Claudia Vergelli、Stefano Pieretti、Vittorio Dal Piaz、Maria Paola Giovannoni

  DOI：10.1021/jm900592h

  日期：2009.8.27

  Following a ligand-based drug design approach, a potent mixed formyl peptide receptor I (FPR1) and formyl peptide receptor-like I (FPRL1) agonist (14a) and a potent and specific FPRL1 agonist (14x) were identified. These compounds belong to a large series of pyridazin-3(2H)-one derivatives substituted with methyl group at position 6 and a methoxy benzyl at position 4. At position 2, an acetamide side chain is essential for activity. Likewise, the presence of lipophilic and/or electronegative substituents in the position para to the aryl group at the end of the chain plays a critical role for activity. Affinity for FPR1 receptors was evaluated by measuring intracellular calcium flux in HL-60 cells transfected with FPR1, FPRL1, and FPRL2, Agonists were able to activate intracellular calcium mobilization and chemotaxis in human neutrophils. The most potent chemotactic agent (EC50 = 0.6 mu M) was the mixed FPR/FPRL1 agonist 14h.