1-methyl-N-(4-piperidinylmethyl)-1H-indazole-3-carboxamide | 1404057-54-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡唑类
• 英文名称: 1-methyl-N-(4-piperidinylmethyl)-1H-indazole-3-carboxamide
• 英文别名: 1-methyl-N-(piperidin-4-ylmethyl)indazole-3-carboxamide
• CAS: 1404057-54-0
• 化学式: C₁₅H₂₀N₄O
• 分子量: 272.35
• InChiKey: OKEQVVIGLLFCKW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  59
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-methyl-N-(4-piperidinylmethyl)-1H-indazole-3-carboxamide 在 potassium carbonate 作用下， 以 乙醇 为溶剂， 反应 2.0h， 生成 1-methyl-N-[[1-(4-phenylbutyl)piperidin-4-yl]methyl]indazole-3-carboxamide;oxalic acid
  参考文献：
  名称：

  Discovery and Pharmacological Profile of New 1H-Indazole-3-carboxamide and 2H-Pyrrolo[3,4-c]quinoline Derivatives as Selective Serotonin 4 Receptor Ligands

  摘要：

  Since the discovery of the serotonin 4 receptor (5-HT4R), a large number of receptor ligands have been studied. The safety concerns and the lack of market success of these ligands have mainly been attributed to their lack of selectivity. In this study we describe the discovery of N-[(4- piperidinyl)methyl]-1H-indazole-3-carboxamide and 4-[(4-piperidinyl)methoxy]-2H-pyrrolo[3,4-c]quinoline derivatives as new 5-HT4R ligands endowed with high selectivity over the serotonin 2A receptor and human ether-a-go-go-related gene potassium ion channel. Within these series, two molecules (11ab and 12g) were identified as potent and selective 5-HT4R antagonists with good in vitro pharmacokinetic properties. These compounds were evaluated for their antinociceptive action in two analgesia animal models. 12g showed a significant antinociceptive effect in both models and is proposed as an interesting lead compound as a 5-HT4R antagonist with analgesic action.

  DOI：

  10.1021/jm300573d
• 作为产物：
  描述：

  1-甲基-1H-吲唑-3-甲酰氯 在 palladium 10% on activated carbon 、 氢气 作用下， 以 乙醇 、 溶剂黄146 、 甲苯 为溶剂， 20.0 ℃ 、193.06 kPa 条件下， 反应 36.0h， 生成 1-methyl-N-(4-piperidinylmethyl)-1H-indazole-3-carboxamide
  参考文献：
  名称：

  Discovery and Pharmacological Profile of New 1H-Indazole-3-carboxamide and 2H-Pyrrolo[3,4-c]quinoline Derivatives as Selective Serotonin 4 Receptor Ligands

  摘要：

  Since the discovery of the serotonin 4 receptor (5-HT4R), a large number of receptor ligands have been studied. The safety concerns and the lack of market success of these ligands have mainly been attributed to their lack of selectivity. In this study we describe the discovery of N-[(4- piperidinyl)methyl]-1H-indazole-3-carboxamide and 4-[(4-piperidinyl)methoxy]-2H-pyrrolo[3,4-c]quinoline derivatives as new 5-HT4R ligands endowed with high selectivity over the serotonin 2A receptor and human ether-a-go-go-related gene potassium ion channel. Within these series, two molecules (11ab and 12g) were identified as potent and selective 5-HT4R antagonists with good in vitro pharmacokinetic properties. These compounds were evaluated for their antinociceptive action in two analgesia animal models. 12g showed a significant antinociceptive effect in both models and is proposed as an interesting lead compound as a 5-HT4R antagonist with analgesic action.

  DOI：

  10.1021/jm300573d

文献信息

• Discovery and Pharmacological Profile of New 1<i>H</i>-Indazole-3-carboxamide and 2<i>H</i>-Pyrrolo[3,4-<i>c</i>]quinoline Derivatives as Selective Serotonin 4 Receptor Ligands
  作者：Guido Furlotti、Maria Alessandra Alisi、Claudia Apicella、Alessandra Capezzone de Joannon、Nicola Cazzolla、Roberta Costi、Giuliana Cuzzucoli Crucitti、Beatrice Garrone、Alberto Iacovo、Gabriele Magarò、Giorgina Mangano、Gaetano Miele、Rosella Ombrato、Luca Pescatori、Lorenzo Polenzani、Federica Rosi、Marco Vitiello、Roberto Di Santo

  DOI：10.1021/jm300573d

  日期：2012.11.26

  Since the discovery of the serotonin 4 receptor (5-HT4R), a large number of receptor ligands have been studied. The safety concerns and the lack of market success of these ligands have mainly been attributed to their lack of selectivity. In this study we describe the discovery of N-[(4- piperidinyl)methyl]-1H-indazole-3-carboxamide and 4-[(4-piperidinyl)methoxy]-2H-pyrrolo[3,4-c]quinoline derivatives as new 5-HT4R ligands endowed with high selectivity over the serotonin 2A receptor and human ether-a-go-go-related gene potassium ion channel. Within these series, two molecules (11ab and 12g) were identified as potent and selective 5-HT4R antagonists with good in vitro pharmacokinetic properties. These compounds were evaluated for their antinociceptive action in two analgesia animal models. 12g showed a significant antinociceptive effect in both models and is proposed as an interesting lead compound as a 5-HT4R antagonist with analgesic action.