5-methyl-4-oxo-8-(3,5-dimethyl-1H-pyrazol-4-yl)-1,4-dihydroquinoline-2-carboxylic acid (4-morpholin-4-yl-phenyl)amide | 1206912-68-6

• 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: 5-methyl-4-oxo-8-(3,5-dimethyl-1H-pyrazol-4-yl)-1,4-dihydroquinoline-2-carboxylic acid (4-morpholin-4-yl-phenyl)amide
• 英文别名: 8-(3,5-dimethyl-1H-pyrazol-4-yl)-5-methyl-N-(4-morpholin-4-ylphenyl)-4-oxo-1H-quinoline-2-carboxamide
• CAS: 1206912-68-6
• 化学式: C₂₆H₂₇N₅O₃
• 分子量: 457.532
• InChiKey: VUHQMJMGDDIHTP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  34
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  99.4
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  3,5-二甲基吡唑-4-硼酸频那醇酯 、 8-bromo-5-methyl-4-oxo-1,4-dihydroquinoline-2-carboxylic acid (4-morpholin-4-ylphenyl)amide 在 bis-triphenylphosphine-palladium(II) chloride 、 potassium carbonate 作用下， 以 四氢呋喃 、 乙醇 、 水 为溶剂， 反应 3.0h， 以5%的产率得到5-methyl-4-oxo-8-(3,5-dimethyl-1H-pyrazol-4-yl)-1,4-dihydroquinoline-2-carboxylic acid (4-morpholin-4-yl-phenyl)amide
  参考文献：
  名称：

  De Novo Design of a Picomolar Nonbasic 5-HT_1B Receptor Antagonist

  摘要：

  We describe herein the discovery of novel, de novo designed, 5-HT1B receptor antagonists that lack a basic moiety and that provide improved hERG and in vitro phospholipidosis profiles. We used a known 5-HT1B antagonist template as our starting point and focused on replacing the piperazine moiety. Pyrazole-based ideas were designed and synthesized among a small library of piperazine replacements. To our knowledge, these are the first potent, nonbasic, functionally active antagonists of the 5-HT1B receptor.

  DOI：

  10.1021/jm901200t

文献信息

• De Novo Design of a Picomolar Nonbasic 5-HT_1B Receptor Antagonist
  作者：David A. Nugiel、Jennifer R. Krumrine、Daniel C. Hill、James R. Damewood、Peter R. Bernstein、Cynthia D. Sobotka-Briner、JianWei Liu、Anna Zacco、M. Edward Pierson

  DOI：10.1021/jm901200t

  日期：2010.2.25

  We describe herein the discovery of novel, de novo designed, 5-HT1B receptor antagonists that lack a basic moiety and that provide improved hERG and in vitro phospholipidosis profiles. We used a known 5-HT1B antagonist template as our starting point and focused on replacing the piperazine moiety. Pyrazole-based ideas were designed and synthesized among a small library of piperazine replacements. To our knowledge, these are the first potent, nonbasic, functionally active antagonists of the 5-HT1B receptor.