6-methyl-N-[6-[(2-chloro-3-pyridinyl)oxy]-3-pyridinyl]-1H-indole-3-carboxamide | 1190847-01-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 6-methyl-N-[6-[(2-chloro-3-pyridinyl)oxy]-3-pyridinyl]-1H-indole-3-carboxamide
• 英文别名: 6-methyl-1H-indole-3-carboxylic acid [6-(2-chloro-pyridine-3-yloxy)-pyridine-3-yl]-amide；6-Methyl-1h-indole-3-carboxylic acid[6-(2-chloro-pyridine-3-yloxy)-pyridine-3-yl]-amide；N-[6-(2-chloropyridin-3-yl)oxypyridin-3-yl]-6-methyl-1H-indole-3-carboxamide
• CAS: 1190847-01-8
• 化学式: C₂₀H₁₅ClN₄O₂
• 分子量: 378.818
• InChiKey: KMFWYMVCBRGXIR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  27
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.05
• 拓扑面积：
  79.9
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  6-甲基吲哚 在 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 三乙胺 、 sodium hydroxide 作用下， 以 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 15.0h， 生成 6-methyl-N-[6-[(2-chloro-3-pyridinyl)oxy]-3-pyridinyl]-1H-indole-3-carboxamide
  参考文献：
  名称：

  [EN] NOVEL INDOL CARBOXYLIC ACID BISPYRIDYL CARBOXAMIDE DERIVATIVES, PHARMACEUTICALLY ACCEPTABLE SALT THEREOF, PREPARATION METHOD AND COMPOSITION CONTAINING THE SAME AS AN ACTIVE INGREDIENT
  [FR] NOUVEAUX DÉRIVÉS DE BISPYRIDYL CARBOXAMIDE D'ACIDE INDOLE CARBOXYLIQUE, LEURS SELS PHARMACEUTIQUEMENT ACCEPTABLES, PROCÉDÉ DE PRÉPARATION ET COMPOSITION LES CONTENANT EN TANT D'INGRÉDIENT ACTIF

  摘要：

  公开号：

  WO2009125923A3

文献信息

• NOVEL INDOL CARBOXYLIC ACID BISPYRIDYL CARBOXAMIDE DERIVATIVES, PHARMACEUTICALLY ACCEPTABLE SALT THEREOF, PREPARATION METHOD AND COMPOSITION CONTAINING THE SAME AS AN ACTIVE INGREDIENT
  申请人：SEONG Churlmin

  公开号：US20090258876A1

  公开（公告）日：2009-10-15

  Disclosed herein are a new indole carboxylic acid bispyridyl carboxamide derivative, a preparation method thereof, and a composition for prevention or treatment of obesity, urinary disorders, and CNS disorders, containing the same as an active ingredient. Because the indole carboxylic acid bispyridyl carboxamide derivatives according to the present invention have high affinity for 5-HT 2c receptors, act selectively on the 5-HT 2c receptors, the derivatives rarely have adverse effects caused by other receptors. Because the derivatives effectively inhibit serotonin activity, they may be useful for treatment or prevention of obesity; urinary disorders such as urinary incontinence, premature ejaculation, erectile dysfunction, and prostatic hyperplasia; CNS disorders such as depression, anxiety, concern, panic disorder, epilepsy, obsessive-compulsive disorder, migraine, sleep disorder, withdrawal from drug abuse, Alzheimer's disease, and schizophrenia, associated with 5-HT 2c receptors.

  本公开涉及一种新的吲哚羧酸双吡啶羧酰胺衍生物，其制备方法，以及包含该衍生物作为活性成分的用于预防或治疗肥胖、泌尿系统疾病和中枢神经系统疾病的组合物。根据本发明的吲哚羧酸双吡啶羧酰胺衍生物具有高亲和力5-HT2c受体，对5-HT2c受体选择性作用，这些衍生物很少出现由其他受体引起的不良反应。由于这些衍生物有效抑制5-羟色胺活性，它们可能对治疗或预防肥胖；泌尿系统疾病，如尿失禁、早泄、勃起功能障碍和前列腺增生；以及与5-HT2c受体相关的中枢神经系统疾病，如抑郁症、焦虑症、关注症、恐慌症、癫痫、强迫症、偏头痛、睡眠障碍、戒毒、阿尔茨海默病和精神分裂症可能有用。
• Synthesis and Evaluation of Pyridyloxypyridyl Indole Carboxamides as Potential PET Imaging Agents for 5-HT_2C Receptors
  作者：Fanxing Zeng、Jonathon A. Nye、Ronald J. Voll、Leonard Howell、Mark M. Goodman

  DOI：10.1021/acsmedchemlett.7b00443

  日期：2018.3.8

  synthesized by palladium-catalyzed coupling reaction between pinacolboranate 16 and [11C]CH3I with an average radiochemical yield of 27 ± 4% (n = 8, decay-corrected from end of [11C]CH3I synthesis). MicroPET imaging studies in rhesus monkeys showed regional uptake of [11C]8 in the choroid plexus, whereas the bindings in all other brain regions were low. The specific binding in the choroid plexus was

  合成了九种吡啶氧基氧基吡啶基吲哚羧酰胺，它们显示出对5-HT2C受体的高亲和力和对5-HT2A和5-HT2B的高选择性。其中，6-甲基-N- [6-[（2-甲基-3-吡啶基）氧基] -3-吡啶基] 1H-吲哚-3-羧酰胺（8）表现出最高的5-HT2C结合亲和力（Ki = 1.3 nM）和对5-HT2A（〜1000倍）和5-HT2B（〜140倍）的高选择性。[11C] 8是通过频哪醇硼酸酯16与[11C] CH3I之间的钯催化偶联反应合成的，平均放射化学产率为27±4％（n = 8，从[11C] CH3I合成结束时进行衰减校正）。在恒河猴中的MicroPET成像研究显示脉络丛中[11C] 8的区域摄取，而在所有其他脑区域中的结合均很低。通过给予0的阻断剂量可以确认脉络丛中的特异性结合。
• Indol carboxylic acid bispyridyl carboxamide derivatives, pharmaceutically acceptable salt thereof, preparation method and composition containing the same as an active ingredient
  申请人：Korea Research Institute of Chemical Technology

  公开号：US08324246B2

  公开（公告）日：2012-12-04

  Disclosed herein are a new indole carboxylic acid bispyridyl carboxamide derivative, a preparation method thereof, and a composition for prevention or treatment of obesity, urinary disorders, and CNS disorders, containing the same as an active ingredient. Because the indole carboxylic acid bispyridyl carboxamide derivatives according to the present invention have high affinity for 5-HT2c receptors, act selectively on the 5-HT2c receptors, the derivatives rarely have adverse effects caused by other receptors. Because the derivatives effectively inhibit serotonin activity, they may be useful for treatment or prevention of obesity; urinary disorders such as urinary incontinence, premature ejaculation, erectile dysfunction, and prostatic hyperplasia; CNS disorders such as depression, anxiety, concern, panic disorder, epilepsy, obsessive-compulsive disorder, migraine, sleep disorder, withdrawal from drug abuse, Alzheimer's disease, and schizophrenia, associated with 5-HT2c receptors.

  本发明公开了一种新的吲哚羧酸双吡啶基羧酰胺衍生物、其制备方法以及一种包含该衍生物作为活性成分的用于预防或治疗肥胖症、泌尿系统疾病和中枢神经系统疾病的组合物。由于本发明中的吲哚羧酸双吡啶基羧酰胺衍生物具有对5-HT2c受体的高亲和力，选择性地作用于5-HT2c受体，因此衍生物很少产生其他受体引起的不良反应。由于该衍生物能够有效抑制5-HT2c受体的血清素活性，因此可能对治疗或预防肥胖症、泌尿系统疾病（如尿失禁、早泄、勃起功能障碍和前列腺增生）以及与5-HT2c受体相关的中枢神经系统疾病（如抑郁症、焦虑症、担心症、惊恐障碍、癫痫、强迫症、偏头痛、睡眠障碍、药物滥用戒断、阿尔茨海默病和精神分裂症）有用。
• Novel indol carboxylic acid bispyridyl carboxamide derivatives as 5-HT2c receptor antagonists
  申请人：KOREA RESEARCH INSTITUTE OF CHEMICAL TECHNOLOGY

  公开号：EP2108649B1

  公开（公告）日：2013-04-24
• US8324246B2
  申请人：——

  公开号：US8324246B2

  公开（公告）日：2012-12-04