1-isopropyl-N-[[1-[2-(4-hydroxyphenyl)ethyl]-4-piperidinyl]-methyl]-1H-indazole-3-carboxamide | 845713-45-3

• 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-isopropyl-N-[[1-[2-(4-hydroxyphenyl)ethyl]-4-piperidinyl]-methyl]-1H-indazole-3-carboxamide
• 英文别名: N-[[1-[2-(4-hydroxyphenyl)ethyl]piperidin-4-yl]methyl]-1-propan-2-ylindazole-3-carboxamide
• CAS: 845713-45-3
• 化学式: C₂₅H₃₂N₄O₂
• 分子量: 420.555
• InChiKey: SMPAXQNASQVLJD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  31
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  70.4
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-isopropyl-N-[[1-[2-(4-hydroxyphenyl)ethyl]-4-piperidinyl]-methyl]-1H-indazole-3-carboxamide 在 盐酸 作用下， 以 乙醇 为溶剂， 生成 N((1-(2-(4-hydroxyphenyl)ethyl)-4-piperidinyl)methyl)-1-isopropyl-1H-indazole-3-carboxamide hydrochloride
  参考文献：
  名称：

  [EN] USE OF INDAZOLE DERIVATIVES FOR THE TREATMENT OF NEUROPATHIC PAIN
  [FR] DERIVES D'INDAZOL UTILISES POUR TRAITER LES DOULEURS NEUROPATHIQUES

  摘要：

  使用公式（I）的化合物，其中X为CH或N，当X为CH时，R为H，OH，具有1至3个碳原子的直链或支链烷基链，具有1至3个碳原子的直链或支链烷氧基链或卤素原子，当X为N时，R为H或其与药用可接受的有机或无机酸的酸加盐，用于制备治疗神经病性疼痛的药物组合物。

  公开号：

  WO2005013989A1
• 作为产物：
  描述：

  1-苄基哌啶-4-甲胺 在 盐酸 、 palladium 10% on activated carbon 、 氢气 、 potassium carbonate 作用下， 以 乙醇 、 溶剂黄146 、 甲苯 为溶剂， 20.0 ℃ 、241.32 kPa 条件下， 反应 38.0h， 生成 1-isopropyl-N-[[1-[2-(4-hydroxyphenyl)ethyl]-4-piperidinyl]-methyl]-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

• [EN] USE OF INDAZOLE DERIVATIVES FOR THE TREATMENT OF NEUROPATHIC PAIN<br/>[FR] DERIVES D'INDAZOL UTILISES POUR TRAITER LES DOULEURS NEUROPATHIQUES
  申请人：ACRAF

  公开号：WO2005013989A1

  公开（公告）日：2005-02-17

  Use of a compound of formula (I), wherein X is CH or N, and when X is CH, R is H, OH, a linear or branched alkyl chain having from 1 to 3 carbon atoms, a linear or branched alkoxy chain having from 1 to 3 carbon atoms, or a halogen atom, and when X is N, R is H, or an acid addition salt thereof with a pharmaceutically acceptable organic or inorganic acid, to prepare a pharmaceutical composition active in the treatment of neuropathic pain.

  使用公式（I）的化合物，其中X为CH或N，当X为CH时，R为H，OH，具有1至3个碳原子的直链或支链烷基链，具有1至3个碳原子的直链或支链烷氧基链或卤素原子，当X为N时，R为H或其与药用可接受的有机或无机酸的酸加盐，用于制备治疗神经病性疼痛的药物组合物。
• 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.