[5-(3-methoxybenzyl)-3-methyl-6-oxo-6H-pyridazin-1-yl]acetic acid | 1184304-26-4

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: [5-(3-methoxybenzyl)-3-methyl-6-oxo-6H-pyridazin-1-yl]acetic acid
• 英文别名: 2-[5-[(3-Methoxyphenyl)methyl]-3-methyl-6-oxopyridazin-1-yl]acetic acid
• CAS: 1184304-26-4
• 化学式: C₁₅H₁₆N₂O₄
• 分子量: 288.303
• InChiKey: BKSVTXHTUKSRHI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  21
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  79.2
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  [5-(3-methoxybenzyl)-3-methyl-6-oxo-6H-pyridazin-1-yl]acetic acid 、 对三氟甲氧基苯胺 在 三乙胺 、 氯甲酸乙酯 作用下， 以 四氢呋喃 为溶剂， 反应 13.0h， 以87%的产率得到2-[5-(3-methoxybenzyl)-3-methyl-6-oxo-6H-pyridazin-1-yl]-N-(4-trifluoromethoxyphenyl)-acetamide
  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 在 potassium carbonate 、 sodium hydroxide 作用下， 以 乙腈 为溶剂， 生成 [5-(3-methoxybenzyl)-3-methyl-6-oxo-6H-pyridazin-1-yl]acetic acid
  参考文献：
  名称：

  新型基于哒嗪酮的硫代衍生物作为甲酰肽受体（FPR）激动剂的合成及药理评价

  摘要：

  临床前研究

  DOI：

  10.1002/ddr.21076

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.
• Synthesis and Pharmacological Evaluation of New Pyridazin-Based Thioderivatives as Formyl Peptide Receptor (FPR) Agonists
  作者：Letizia Crocetti、Claudia Vergelli、Agostino Cilibrizzi、Alessia Graziano、Andrei I. Khlebnikov、Liliya N. Kirpotina、Igor A. Schepetkin、Mark T. Quinn、Maria Paola Giovannoni

  DOI：10.1002/ddr.21076

  日期：2013.6

  Preclinical Research

  临床前研究