1-isopropyl-N-(4-piperidinylmethyl)-1H-indazole-3-carboxamide | 214707-91-2

• 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
• 英文别名: 1-isopropyl-1H-indazole-3-carboxylic acid (piperidin-4-ylmethyl)amide；N-(4-piperidinylmethyl)-1-isopropyl-1H-3-indazolecarboxamide；n-(4-Piperidinylmethyl)-1-isopropyl-1h-3 indazolecarboxamide；N-(piperidin-4-ylmethyl)-1-propan-2-ylindazole-3-carboxamide
• CAS: 214707-91-2
• 化学式: C₁₇H₂₄N₄O
• 分子量: 300.404
• InChiKey: CRKKBLJOBGERJR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  22
• 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：
  2
• 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 在 potassium carbonate 作用下， 以 乙醇 为溶剂， 反应 2.0h， 生成 N-[[1-[3-(dimethylamino)propyl]-4-piperidinyl]methyl]-1-isopropyl-1H-indazole-3-carboxamide dimaleic 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-苄基哌啶-4-甲胺 在 盐酸 、 palladium 10% on activated carbon 、 氢气 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 36.0h， 生成 1-isopropyl-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 Preclinical Characterization of Usmarapride (SUVN-D4010): A Potent, Selective 5-HT₄Receptor Partial Agonist for the Treatment of Cognitive Deficits Associated with Alzheimer’s Disease
  作者：Ramakrishna Nirogi、Abdul Rasheed Mohammed、Anil Karbhari Shinde、Shankar Reddy Gagginapally、Durga Malleshwari Kancharla、Srinivasa Rao Ravella、Narsimha Bogaraju、Vanaja Reddy Middekadi、Ramkumar Subramanian、Raghava Choudary Palacharla、Vijay Benade、Nageswararao Muddana、Renny Abraham、Rajesh Babu Medapati、Jagadeesh Babu Thentu、Venkat Reddy Mekala、Surendra Petlu、Bujji Babu Lingavarapu、Sivasekhar Yarra、Narendra Kagita、Vinod Kumar Goyal、Santosh Kumar Pandey、Venkat Jasti

  DOI：10.1021/acs.jmedchem.1c00703

  日期：2021.8.12

  A series of oxadiazole derivatives were synthesized and evaluated as 5-hydroxytryptamine-4 receptor (5-HT4R) partial agonists for the treatment of cognitive deficits associated with Alzheimer’s disease. Starting from a reported 5-HT4R antagonist, a systematic structure–activity relationship was conducted, which led to the discovery of potent and selective 5-HT4R partial agonist 1-isopropyl-3-5-[1-(3-methoxypropyl)

  合成并评估了一系列恶二唑衍生物作为 5-羟色胺-4 受体 (5-HT 4 R) 部分激动剂，用于治疗与阿尔茨海默病相关的认知缺陷。从报道的 5-HT 4 R 拮抗剂开始，进行了系统的构效关系，从而发现了有效和选择性的 5-HT 4 R 部分激动剂 1-异丙基-3-5-[1-(3 -甲氧基丙基）哌啶-4-基]-[1,3,4]恶二唑-2-基}-1H-吲唑草酸盐（Usmarapride，12l）。它在认知模型中表现出平衡的理化-药代动力学特性，具有强大的非临床功效。它还显示出改善疾病的潜力，因为它增加了神经保护性可溶性淀粉样前体蛋白 α 水平，以及剂量依赖性靶标参与和功效与口服暴露的相关性。1 期临床研究已完成，预计有效浓度已达到，没有任何重大安全问题。实现长期安全性研究的第 2 阶段已经完成，无需担心进一步开发。
• [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。
• Use of indazole derivatives for the treatment of neuropathic pain
  申请人：Guglielmotti Angelo

  公开号：US20060183775A1

  公开（公告）日：2006-08-17

  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个碳原子的线性或分支烷基链，具有1至3个碳原子的线性或分支烷氧基链，或卤素原子，当X为N时，R为H，或其与药学上可接受的有机或无机酸的酸加成盐，以制备用于治疗神经病性疼痛的药物组合物。
• 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：EP0975623A2

  公开（公告）日：2000-02-02
• USE OF INDAZOLE DERIVATIVES FOR THE TREATMENT OF NEUROPATHIC PAIN
  申请人：AZIENDE CHIMICHE RIUNITE ANGELINI FRANCESCO A.C.R.A.F. S.p.A.

  公开号：EP1646387B1

  公开（公告）日：2006-11-15