1'-(5-carboxy-1H-benzimidazol-2-yl)-spiro[isobenzofuran-1,4'-piperidin]-3-one | 1075753-12-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并呋喃
• 英文名称: 1'-(5-carboxy-1H-benzimidazol-2-yl)-spiro[isobenzofuran-1,4'-piperidin]-3-one
• 英文别名: 2-(3-oxo-3H-spiro[isobenzofuran-1,4''-piperidine]-1''-yl)-1H-benzo[d]imidazole-5-carboxylic acid；2-(3-oxospiro[2-benzofuran-1,4'-piperidine]-1'-yl)-3H-benzimidazole-5-carboxylic acid
• CAS: 1075753-12-6
• 化学式: C₂₀H₁₇N₃O₄
• 分子量: 363.373
• InChiKey: UFUKIJYVRWRXGP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  27
• 可旋转键数：
  2
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  95.5
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  在 三氟乙酸 作用下， 生成 1'-(5-carboxy-1H-benzimidazol-2-yl)-spiro[isobenzofuran-1,4'-piperidin]-3-one
  参考文献：
  名称：

  Design, syntheses, and structure–activity relationships of novel NPY Y5 receptor antagonists: 2-{3-Oxospiro[isobenzofuran-1(3H),4′-piperidin]-1′-yl}benzimidazole derivatives

  摘要：

  Design, syntheses, and structure-activity relationships of a novel class of 2-{3-oxospiro[isobenzofuran-1(3H),4'-piperidin]-1'-yl}benzimidazole NPY Y5 receptor antagonists are described. The benzimidazole structures were newly designed based on the urea linkage of our prototype Y5 receptor antagonists (2 and 3). By optimizing substituents on the benzimidazole core part of the lead compound 5a, we were able to develop a potent, orally available, and brain-penetrable Y5 selective antagonist (5k). Crown Copyright (C) 2008 Published by Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2008.08.018

文献信息

• Spiro[isobenzofuran-1,4'-piperidin]-3-ones and 3H-spiroisobenzofuran-1,4'-piperidines
  申请人：NEUROGEN CORPORATION

  公开号：US20030036652A1

  公开（公告）日：2003-02-20

  Substituted spiro[isobenzofuran-1,4′-piperidin]-3-ones and 3H-spiroisobenzofuran-1,4′-piperidines capable of modulating NPY5 receptor activity are provided. Such compounds may be used to modulate ligand binding to NPY5 receptors in vivo or in vitro, and are particularly useful in the treatment of a variety of disorders (e.g., eating disorders such as obesity or bulimia, psychiatric disorders, diabetes and cardiovascular disorders such as hypertension) in humans, domesticated companion animals and livestock animals. Pharmaceutical compositions and methods for treating such disorders are provided, as are methods for using such compounds for detecting NPY5 receptors.

  提供了能够调节NPY5受体活性的替代螺环[异苯并呋喃-1,4′-哌啶]-3-酮和3H-螺环异苯并呋喃-1,4′-哌啶。这些化合物可用于在体内或体外调节NPY5受体的配体结合，并且在治疗各种疾病（例如，肥胖或暴食症等进食障碍、精神障碍、糖尿病和高血压等心血管疾病）方面对人类、驯养的伴侣动物和家畜动物特别有用。提供了用于治疗这些疾病的药物组合物和方法，以及用于检测NPY5受体的这些化合物的方法。
• Spiro[isobenzofuran-1,4'-piperidin]-3-ones and 3h-spiroisobenzofuran-1,4'-piperidines
  申请人：Bakthavatchalam Rajagopal

  公开号：US20050033048A1

  公开（公告）日：2005-02-10

  Substituted spiro[isobenzofuran-1,4′-piperidin]-3-ones and 3H-spiroisobenzofuran-1,4′-piperidines capable of modulating NPY5 receptor activity are provided. Such compounds may be used to modulate ligand binding to NPY5 receptors in vivo or in vitro, and are particularly useful in the treatment of a variety of disorders (e.g., eating disorders such as obesity or bulimia, psychiatric disorders, diabetes and cardiovascular disorders such as hypertension) in humans, domesticated companion animals and livestock animals. Pharmaceutical compositions and method for treating such disorders are provided, as are methods for using such compounds for detecting NPY5 receptors.

  本文提供了能够调节NPY5受体活性的取代的spiro[异苯并呋喃-1,4'-哌啶]-3-酮和3H-spiro异苯并呋喃-1,4'-哌啶。这些化合物可以用于体内或体外调节NPY5受体的配体结合，并且在人类、宠物和家畜动物的多种疾病治疗中特别有用（例如，饮食失调如肥胖症或贪食症、精神障碍、糖尿病和心血管疾病如高血压）。提供了制药组合物和治疗这些疾病的方法，以及使用这些化合物检测NPY5受体的方法。
• Spiro [isobenzofuran-1,4'piperidin]-3-ones and 3H-spiroisobenzofuran-1, 4'-piperidines
  申请人：NEUROGEN CORPORATION

  公开号：EP1695977A2

  公开（公告）日：2006-08-30

  This invention relates generally to substituted spiro[isobenzofuran-1,4'-piperidin]-3-ones and 3H-spiroisobenzofuran-1,4'-piperidines that are modulators of mammalian neuropeptide Y5 (NPY5) receptors, and to the use of such compounds for treating a variety of physiological disorders associated with NPY5 receptor activation, such as feeding disorders, psychiatric disorders and cardiovascular diseases. The invention further relates to the use such compounds as probes for the detection and localization of NPY5 receptors.

  本发明一般涉及取代的螺[异苯并呋喃-1,4'-哌啶]-3-酮和3H-螺异苯并呋喃-1,4'-哌啶，它们是哺乳动物神经肽Y5（NPY5）受体的调节剂，本发明还涉及使用此类化合物治疗与NPY5受体激活有关的各种生理紊乱，如进食紊乱、精神紊乱和心血管疾病。本发明进一步涉及将此类化合物用作检测和定位 NPY5 受体的探针。
• Treatment of circadian rhythm disorders with NPY Y5 receptor antagonist
  申请人：Matos Fatima Francisca

  公开号：US20050119283A1

  公开（公告）日：2005-06-02

  A method for treating circadian rhythm disorders in mammals comprising administering to a mammal an effective amount of an NPY Y5 receptor antagonist. In particular, a method is provided for enhancing the effects of light on circadian rhythm.

  一种治疗哺乳动物昼夜节律紊乱的方法，包括向哺乳动物施用有效量的 NPY Y5 受体拮抗剂。特别是提供了一种增强光对昼夜节律影响的方法。
• Treatment of neurological disorders related to rapid eye movement (REM) sleep disturbances with NPY Y5 receptor antagonists
  申请人：Matos Fatima Francisca

  公开号：US20050119285A1

  公开（公告）日：2005-06-02

  This invention relates to a method for treating and preventing neurological disorders related to rapid-eye-movement (REM) sleep disturbances in a mammal comprising administering to the mammal an amount of an NPY Y5 receptor antagonist which effectively reduces REM sleep.

  本发明涉及一种治疗和预防与哺乳动物快速眼动（REM）睡眠障碍有关的神经系统疾病的方法，该方法包括向哺乳动物施用一定量的 NPY Y5 受体拮抗剂，这种拮抗剂可有效减少快速眼动睡眠。