4-{2-[4-({[(1-isopropyl-1H-indazol-3-yl)carbonyl]-amino}methyl)piperidin-1-yl]ethyl}benzoic acid | 1152431-13-4

• 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: 4-{2-[4-({[(1-isopropyl-1H-indazol-3-yl)carbonyl]-amino}methyl)piperidin-1-yl]ethyl}benzoic acid
• 英文别名: 4-[2-[4-[[(1-Propan-2-ylindazole-3-carbonyl)amino]methyl]piperidin-1-yl]ethyl]benzoic acid
• CAS: 1152431-13-4
• 化学式: C₂₆H₃₂N₄O₃
• 分子量: 448.565
• InChiKey: IIDIAHIVYVSCHD-UHFFFAOYSA-N

物化性质

• 熔点：
  180-182 °C
• 沸点：
  680.2±40.0 °C(predicted)
• 密度：
  1.25±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  33
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  87.5
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  1-苄基哌啶-4-甲胺 在 盐酸 、 palladium 10% on activated carbon 、 氢气 、 三乙胺 、 sodium hydroxide 作用下， 以 四氢呋喃 、 乙醇 、 溶剂黄146 、 甲苯 、 丁酮 为溶剂， 20.0 ℃ 、241.32 kPa 条件下， 反应 84.0h， 生成 4-{2-[4-({[(1-isopropyl-1H-indazol-3-yl)carbonyl]-amino}methyl)piperidin-1-yl]ethyl}benzoic 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

文献信息

• [EN] DRUG ACTIVE IN NEUROPATHIC PAIN<br/>[FR] MÉDICAMENT ACTIF DANS LA DOULEUR NEUROPATHIQUE
  申请人：ACRAF

  公开号：WO2009062883A1

  公开（公告）日：2009-05-22

  The present invention relates to a compound of formula (I): in which: R is a linear or branched alkyl group containing between 1 and 3 carbon atoms, Y is CH or N, and p is an integer between 0 and 3 and preferably 0 and 1, and salts thereof, either acid-addition salts with a pharmaceutically acceptable organic or mineral acid, or base-addition salts with a pharmaceutically acceptable organic or mineral base. The invention also relates to a process for preparing the compound of formula (I), and to a pharmaceutical composition comprising it. The invention also relates to the use of an indazole for preparing a pharmaceutical composition that is active in the treatment of neuropathic pain.

  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。
• 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
• 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.