1-[6-(4-fluorophenyl)pyridin-3-yl]-3-(4-piperidin-1-ylbutyl)urea | 1204607-09-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 1-[6-(4-fluorophenyl)pyridin-3-yl]-3-(4-piperidin-1-ylbutyl)urea
• 英文别名: WYE-103914；SEN34625；1-[6-(4-Fluoro-phenyl)-pyridin-3-yl]-3-(4-piperidin-1-yl-butyl)-urea
• CAS: 1204607-09-9
• 化学式: C₂₁H₂₇FN₄O
• 分子量: 370.47
• InChiKey: LMGUUVWYFJIKCD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  27
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  57.3
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-[6-(4-fluorophenyl)pyridin-3-yl]-3-(4-piperidin-1-ylbutyl)urea 在 盐酸 作用下， 以 乙醚 、 二氯甲烷 为溶剂， 以80%的产率得到1-[6-(4-Fluoro-phenyl)-pyridin-3-yl]-3-(4-piperidin-1-yl-butyl)-urea hydrochloride
  参考文献：
  名称：

  ALPHA7 NICOTINIC ACETYLCHOLINE RECEPTOR INHIBITORS

  摘要：

  本发明提供了化合物和组合物，制备它们的方法，以及利用它们调节α7烟碱乙酰胆碱受体和/或治疗各种疾病、疾病和症状的方法。提供的化合物可以影响神经系统、精神病和/或炎症系统等方面。

  公开号：

  US20100016598A1
• 作为产物：
  描述：

  1-(6-bromo-pyridin-3-yl)-3-(4-piperidin-1-yl-butyl)-urea hydrochloride 、 4-氟苯硼酸 在 bis-triphenylphosphine-palladium(II) chloride potassium carbonate 作用下， 以 乙醇 为溶剂， 以92%的产率得到1-[6-(4-fluorophenyl)pyridin-3-yl]-3-(4-piperidin-1-ylbutyl)urea
  参考文献：
  名称：

  ALPHA7 NICOTINIC ACETYLCHOLINE RECEPTOR INHIBITORS

  摘要：

  本发明提供了化合物和组合物，制备它们的方法，以及利用它们调节α7烟碱乙酰胆碱受体和/或治疗各种疾病、疾病和症状的方法。提供的化合物可以影响神经系统、精神病和/或炎症系统等方面。

  公开号：

  US20100016598A1

文献信息

• SELECTIVE ALPHA-7 NICOTINIC RECEPTOR AGONISTS AND METHODS FOR MAKING AND USING THEM
  申请人：THE REGENTS OF THE UNIVERSITY OF CALIFORNIA

  公开号：US20180244653A1

  公开（公告）日：2018-08-30

  In alternative embodiments, provided are selective agonists having a high affinity for the alpha7 nicotinic acetylcholine receptor (α7 nAChR), assays for selectivity of nicotinic receptor subtype and ligand-gated ion channel subtype based on receptor occupation and response, behavioral assessments for reversing cognitive impairment after scopolamine treatment, enhancing memory retention over time, pharmaceutical compositions and formulations and devices comprising them, and methods for making and using them, including characterizing and efficiently assaying them for receptor subtype selectivity. In alternative embodiments, provided are substituted anti 1,2,3-triazoles compounds with high affinity, and selective binding, for the alpha7 nicotine acetylcholine receptor (α7 nAChR), as exemplified by 5-(1-(2-(Piperidin-1-yl)ethyl)-1H-1,2,3-triazol-4-yl)-1H-indole (“IND1”), 5-((quinuclid-3-yl)-1H-1,2,3-triazol-4-yl)-1H-indole (“IND8”) and 3-(4-hydroxyphenyl-1,2,3-triazol-1-yl) quinuclidine (“QND8”). In alternative embodiments, provided are products of manufacture such as pumps, devices, syringes and the like comprising a compound, pharmaceutical composition or formulation as provided herein.

  在另一种实施方式中，提供了对α7尼古丁乙酰胆碱受体（α7 nAChR）具有高亲和力的选择性激动剂，基于受体占据和响应的选择性尼古丁受体亚型和配体门控离子通道亚型的筛选方法，行为评估用于在施用东莨菪碱后逆转认知障碍，随时间增强记忆保留，包括表征和高效筛选受体亚型选择性的制备和使用方法的制药组合物和配方以及包括它们的装置，提供了具有高亲和力和选择性结合的替代抗1,2,3-三唑化合物，例如5-（1-（2-（哌啶-1-基）乙基）-1H-1,2,3-三唑-4-基）-1H-吲哚（“IND1”），5-（（喹啉-3-基）-1H-1,2,3-三唑-4-基）-1H-吲哚（“IND8”）和3-（4-羟基苯基-1,2,3-三唑-1-基）喹啉（“QND8”）。在另一种实施方式中，提供了制造产品，例如泵、装置、注射器等，其中包括本文提供的化合物、制药组合物或配方。
• Selective alpha-7 nicotinic receptor agonists and methods for making and using them
  申请人：The Regents of the University of California

  公开号：US10308638B2

  公开（公告）日：2019-06-04

  In alternative embodiments, provided are selective agonists having a high affinity for the alpha7 nicotinic acetylcholine receptor (α7 nAChR), assays for selectivity of nicotinic receptor subtype and ligand-gated ion channel subtype based on receptor occupation and response, behavioral assessments for reversing cognitive impairment after scopolamine treatment, enhancing memory retention over time, pharmaceutical compositions and formulations and devices comprising them, and methods for making and using them, including characterizing and efficiently assaying them for receptor subtype selectivity. In alternative embodiments, provided are substituted anti 1,2,3-triazoles compounds with high affinity, and selective binding, for the alpha7 nicotine acetylcholine receptor (α7 nAChR), as exemplified by 5-(1-(2-(Piperidin-1-yl)ethyl)-1H-1,2,3-triazol-4-yl)-1H-indole (“IND1”), 5-((quinuclid-3-yl)-1H-1,2,3-triazol-4-yl)-1H-indole (“IND8”) and 3-(4-hydroxyphenyl-1,2,3-triazol-1-yl) quinuclidine (“QND8”). In alternative embodiments, provided are products of manufacture such as pumps, devices, syringes and the like comprising a compound, pharmaceutical composition or formulation as provided herein.

  在另一个实施方案中，提供了对α7烟碱乙酰胆碱受体（α7 nAChR）具有高亲和力的选择性激动剂、基于受体占据和反应的烟碱受体亚型和配体门控离子通道亚型选择性的检测方法、在东莨菪碱治疗后逆转认知障碍的行为评估、随时间增强记忆保持、药物组合物和制剂及包含它们的装置，以及制造和使用它们的方法，包括表征和有效测定它们的受体亚型选择性。在另一种实施方案中，提供了对α7 尼古丁乙酰胆碱受体（α7 nAChR）具有高亲和力和选择性结合的取代抗 1,2,3-三唑化合物、例如 5-(1-(2-(哌啶-1-基)乙基)-1H-1,2,3-三唑-4-基)-1H-吲哚（"IND1"）、5-((奎宁环-3-基)-1H-1,2,3-三唑-4-基)-1H-吲哚（"IND8"）和 3-(4-羟基苯基-1,2,3-三唑-1-基)奎宁环（"QND8"）。在另一种实施方案中，提供了包含本文所提供的化合物、药物组合物或制剂的制造产品，如泵、装置、注射器等。
• Biomarkers predictive of responsiveness to alpha 7 nicotinic acetylcholine receptor activator treatment
  申请人：Novartis AG

  公开号：US11359241B2

  公开（公告）日：2022-06-14

  The invention provides methods for predicting therapeutic responsiveness of a subject suffering from cognitive impairments or dysfunctions, psychotic and/or neurodegenerative disorders to an alpha 7 nicotinic acetylcholine receptor activator treatment.

  本发明提供了预测患有认知障碍或功能障碍、精神病和/或神经退行性疾病的受试者对α7烟碱乙酰胆碱受体激活剂治疗反应性的方法。
• Novel Alpha-7 Nicotinic Acetylcholine Receptor Agonists Containing a Urea Moiety: Identification and Characterization of the Potent, Selective, and Orally Efficacious Agonist 1-[6-(4-Fluorophenyl)pyridin-3-yl]-3-(4-piperidin-1-ylbutyl) Urea (SEN34625/WYE-103914)
  作者：Chiara Ghiron、Simon N. Haydar、Suzan Aschmies、Hendrick Bothmann、Cristiana Castaldo、Giuseppe Cocconcelli、Thomas A. Comery、Li Di、John Dunlop、Tim Lock、Angela Kramer、Dianne Kowal、Flora Jow、Steve Grauer、Boyd Harrison、Salvatore La Rosa、Laura Maccari、Karen L. Marquis、Iolanda Micco、Arianna Nencini、Joanna Quinn、Albert J. Robichaud、Renza Roncarati、Carla Scali、Georg C. Terstappen、Elisa Turlizzi、Michela Valacchi、Maurizio Varrone、Riccardo Zanaletti、Ugo Zanelli

  DOI：10.1021/jm901692q

  日期：2010.6.10

  Alpha-7 nicotinic acetylcholine receptor (alpha 7 nAChR) agonists are promising therapeutic candidates for the treatment of cognitive impairment. We report a series of novel, potent small molecule agonists (4-18) of the alpha 7 nACh R deriving from our continuing efforts in the areas of Alzheimer's disease and schizophrenia. One of the compounds of the series containing a urea moiety (16) was further shown to be a selective agonist of the alpha 7 nAChR with excellent in vitro and in vivo profiles, brain penetration, and oral bioavailability and demonstrated in vivo efficacy in multiple behavioral cognition models. Structural modifications leading to the improved selectivity profile and the biological evaluation of this series of compounds are discussed.
• USE OF NICOTINIC ACETYLCHOLINE RECEPTOR ALPHA 7 ACTIVATORS
  申请人：Novartis AG

  公开号：EP2480228A1

  公开（公告）日：2012-08-01