1-isopropyl-N-(4-piperidinylmethyl)-1H-indazole-3-carboxamide hydrochloride | 214707-77-4

• 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-(4-piperidinylmethyl)-1H-indazole-3-carboxamide hydrochloride
• 英文别名: 1-isopropyl-N-(piperidin-4-ylmethyl)-1H-indazol-3-carboxamide hydrochloride；N-(piperidin-4-ylmethyl)-1-propan-2-ylindazole-3-carboxamide;hydrochloride
• CAS: 214707-77-4
• 化学式: C₁₇H₂₄N₄O*ClH
• 分子量: 336.865
• InChiKey: FZKNVYOUIUTVNM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.77
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  59
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-isopropyl-N-(4-piperidinylmethyl)-1H-indazole-3-carboxamide hydrochloride 、 4-(2-溴乙基)苯甲酸乙酯 在 三乙胺 、 potassium iodide 作用下， 以 丁酮 为溶剂， 反应 4.5h， 生成 ethyl 4-[2-[4-[[[(1-isopropyl-1H-indazol-3-yl)carbonyl]amino]-methyl]-1-piperidinyl]ethyl]benzoate
  参考文献：
  名称：

  [EN] DRUG ACTIVE IN NEUROPATHIC PAIN
  [FR] MÉDICAMENT ACTIF DANS LA DOULEUR NEUROPATHIQUE

  摘要：

  本发明涉及一种化合物的公式（I）：其中：R是含有1至3个碳原子的直链或支链烷基基团，Y是CH或N，p是介于0和3之间的整数，最好是0和1之间，以及其盐，即与药学上可接受的有机酸或矿物酸形成的酸盐，或与药学上可接受的有机碱或矿物碱形成的碱盐。本发明还涉及一种制备公式（I）化合物的方法，以及包含该化合物的药物组合物。本发明还涉及使用吲唑啉制备对神经病性疼痛治疗有效的药物组合物。

  公开号：

  WO2009062883A1
• 作为产物：
  描述：

  1-isopropyl-N-(4-piperidinylmethyl)-1H-indazole-3-carboxamide 在 盐酸 作用下， 以 乙醇 为溶剂， 以1 g的产率得到1-isopropyl-N-(4-piperidinylmethyl)-1H-indazole-3-carboxamide hydrochloride
  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

• INDAZOLE AMIDE COMPOUNDS AS SEROTONINERGIC AGENTS
  申请人：AZIENDE CHIMICHE RIUNITE ANGELINI FRANCESCO A.C.R.A.F. S.p.A.

  公开号：EP0975623B1

  公开（公告）日：2002-06-19
• DRUG ACTIVE IN NEUROPATHIC PAIN
  申请人：Aziende Chimiche Riunite Angelini Francesco A.C.R.A.F. S.p.A.

  公开号：EP2207776A1

  公开（公告）日：2010-07-21
• US6197769B1
  申请人：——

  公开号：US6197769B1

  公开（公告）日：2001-03-06
• US8455519B2
  申请人：——

  公开号：US8455519B2

  公开（公告）日：2013-06-04
• 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.