4-((4-bromophenylthio)methyl)tetrahydro-2H-pyran | 1021169-66-3

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫醚类
• 英文名称: 4-((4-bromophenylthio)methyl)tetrahydro-2H-pyran
• 英文别名: 4-((4-bromophenylthio)methyl)-tetrahydro-2H-pyran；4-[(4-bromophenyl)sulfanylmethyl]oxane
• CAS: 1021169-66-3
• 化学式: C₁₂H₁₅BrOS
• 分子量: 287.221
• InChiKey: WUEQQPQAZGYMQT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  15
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  34.5
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  4-((4-bromophenylthio)methyl)tetrahydro-2H-pyran 在 oxone(R) 、 四(三苯基膦)钯 、 sodium carbonate 作用下， 以 四氢呋喃 、 乙醇 、 水 、 苯 为溶剂， 反应 5.0h， 生成 (R)-2-methyl-1-{2-[4'-(tetrahydro-pyran-4-ylmethanesulfonyl)-biphenyl-4-yl]-ethyl}-pyrrolidine
  参考文献：
  名称：

  Identification of biaryl sulfone derivatives as antagonists of the histamine H3 receptor: Discovery of (R)-1-(2-(4′-(3-methoxypropylsulfonyl)biphenyl-4-yl)ethyl)-2-methylpyrrolidine (APD916)

  摘要：

  The design of a new clinical candidate histamine-H-3 receptor antagonist for the potential treatment of excessive daytime sleepiness (EDS) is described. Phenethyl-R-2-methylpyrrolidine containing biphenylsulfonamide compounds were modified by replacement of the sulfonamide linkage with a sulfone. One compound from this series, 2j (APD916) increased wakefulness in rodents as measured by polysomnography with a duration of effect consistent with its pharmacokinetic properties. The identification of a suitable salt form of 2j allowed it to be selected for further development. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.11.075
• 作为产物：
  描述：

  4-溴甲基四氢吡喃 、 4-溴苯硫酚 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 18.5h， 以89.15%的产率得到4-((4-bromophenylthio)methyl)tetrahydro-2H-pyran
  参考文献：
  名称：

  [EN] SSAO INHIBITORS AND USE THEREOF
  [FR] INHIBITEURS DE SSAO ET LEUR UTILISATION

  摘要：

  提供了一个化合物的公式(I')或(I)，其药用盐、水合物、溶剂合物、前药、立体异构体或互变异构体，该化合物调节SSAO的活性，一种包括化合物的药物组合物的公式(I')或(I)，以及一种治疗或预防SSAO在其中发挥作用的疾病的方法。

  公开号：

  WO2021083209A1

文献信息

• [EN] SSAO INHIBITORS AND USE THEREOF<br/>[FR] INHIBITEURS DE SSAO ET LEUR UTILISATION
  申请人：ECCOGENE SHANGHAI CO LTD

  公开号：WO2021083209A1

  公开（公告）日：2021-05-06

  Provided are a compound of formula (I') or (I), a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof, which modulates the activity of SSAO, a pharmaceutical composition comprising a compound of formula (I') or (I), and a method of treating or preventing a disease in which SSAO plays a role.

  提供了一个化合物的公式(I')或(I)，其药用盐、水合物、溶剂合物、前药、立体异构体或互变异构体，该化合物调节SSAO的活性，一种包括化合物的药物组合物的公式(I')或(I)，以及一种治疗或预防SSAO在其中发挥作用的疾病的方法。
• BIPHENYL SULFONYL AND PHENYL-HETEROARYL SULFONYL MODULATORS OF THE HISTAMINE H3-RECEPTOR USEFUL FOR THE TREATMENT OF DISORDERS RELATED THERETO
  申请人：Santora Vincent J.

  公开号：US20100240653A1

  公开（公告）日：2010-09-23

  The present invention relates to certain biphenyl sulfonamide derivatives of Formula (Ia) and pharmaceutical compositions thereof that modulate the activity of the histamine H3-receptor. Compounds of the present invention and pharmaceutical compositions thereof are directed to methods useful in the treatment of histamine H3-associated disorders, such as, cognitive disorders, epilepsy, brain trauma, depression, obesity, disorders of sleep and wakefulness such as narcolepsy, shift-work syndrome, drowsiness as a side effect from a medication, maintenance of vigilance to aid in completion of tasks and the like, cataplexy, hypersomnia, somnolence syndrome, jet lag, sleep apnea and the like, attention deficit hyperactivity disorder (ADHD), schizophrenia, allergies, allergic responses in the upper airway, allergic rhinitis, nasal congestion, dementia, Alzheimer's disease and the like.

  本发明涉及公式（Ia）的某些联苯磺酰胺衍生物及其制药组合物，其调节组织胺H3受体的活性。本发明的化合物和制药组合物适用于治疗组织胺H3相关疾病的方法，例如认知障碍，癫痫，脑外伤，抑郁症，肥胖症，睡眠和清醒障碍，如嗜睡症，倒班综合征，药物副作用引起的嗜睡，维持警觉以帮助完成任务等，猝倒症，过度睡眠症，嗜睡综合征，时差反应，睡眠呼吸暂停等，注意力缺陷多动障碍（ADHD），精神分裂症，过敏症，上呼吸道过敏反应，过敏性鼻炎，鼻塞，痴呆，阿尔茨海默病等。
• WO2008/48609
  申请人：——

  公开号：——

  公开（公告）日：——
• [EN] BIPHENYL SULFONYL AND PHENYL-HETEROARYL SULFONYL MODULATORS OF THE HISTAMINE H3-RECEPTOR USEFUL FOR THE TREATMENT OF DISORDERS RELATED THERETO<br/>[FR] MODULATEURS BIPHÉNYLSULFONYLE ET DE PHÉNYL-HÉTÉRORARYLSULFONYLE DU RECEPTEUR H3 DE L'HISTAMINE UTILES POUR LE TRAITEMENT DE TROUBLES ASSOCIÉS À CELUI-CI
  申请人：ARENA PHARM INC

  公开号：WO2008048609A1

  公开（公告）日：2008-04-24

  [EN] The present invention relates to certain biphenyl sulfonamide derivatives of Formula (Ia) and pharmaceutical compositions thereof that modulate the activity of the histamine H3- receptor. Compounds of the present invention and pharmaceutical compositions thereof are directed to methods useful in the treatment of histamine H3-associated disorders, such as, cognitive disorders, epilepsy, brain trauma, depression, obesity, disorders of sleep and wakefulness such as narcolepsy, shift-work syndrome, drowsiness as a side effect from a medication, maintenance of vigilance to aid in completion of tasks and the like, cataplexy, hypersomnia, somnolence syndrome, jet lag, sleep apnea and the like, attention deficit hyperactivity disorder (ADHD), schizophrenia, allergies, allergic responses in the upper airway, allergic rhinitis, nasal congestion, dementia, Alzheimer's disease and the like.
  [FR] La présente invention concerne certains dérivés biphénylsulfamides selon la formule (Ia) et leurs compositions pharmaceutiques qui modulent l'activité du récepteur H3 de l'histamine. Des composés de la présente invention et leurs compositions pharmaceutiques sont destinés à des procédés utiles dans le traitement de troubles associés au récepteur H3 de l'histamine, tels que des troubles cognitifs, l'épilepsie, les traumatismes crâniens, la dépression, l'obésité, des troubles de la veille et du sommeil tels que la narcolepsie, le syndrome du travail par équipes, l'endormissement en tant qu'effet secondaire d'un médicament, le maintien de la vigilance pour aider à l'accomplissement de tâches et autres activités similaires, la cataplexie, l'hypersomnie, le syndrome de la somnolence, le syndrome du décalage horaire, l'apnée du sommeil et autres conditions similaires, des troubles d'hyperactivité avec déficit d'attention (ADHD), la schizophrénie, les allergies, les réactions allergiques au niveau des voies respiratoires supérieures, la rhinite allergique, la congestion nasale, la démence, la maladie d'Alzheimer et autres maladies similaires.
• Identification of biaryl sulfone derivatives as antagonists of the histamine H3 receptor: Discovery of (R)-1-(2-(4′-(3-methoxypropylsulfonyl)biphenyl-4-yl)ethyl)-2-methylpyrrolidine (APD916)
  作者：Graeme Semple、Vincent J. Santora、Jeffrey M. Smith、Jonathan A. Covel、Rena Hayashi、Charlemagne Gallardo、Jason B. Ibarra、Jeffrey A. Schultz、Douglas M. Park、Scott A. Estrada、Brian J. Hofilena、Brian M. Smith、Albert Ren、Marissa Suarez、John Frazer、Jeffrey E. Edwards、Ryan Hart、Erin K. Hauser、Jodie Lorea、Andrew J. Grottick

  DOI：10.1016/j.bmcl.2011.11.075

  日期：2012.1

  The design of a new clinical candidate histamine-H-3 receptor antagonist for the potential treatment of excessive daytime sleepiness (EDS) is described. Phenethyl-R-2-methylpyrrolidine containing biphenylsulfonamide compounds were modified by replacement of the sulfonamide linkage with a sulfone. One compound from this series, 2j (APD916) increased wakefulness in rodents as measured by polysomnography with a duration of effect consistent with its pharmacokinetic properties. The identification of a suitable salt form of 2j allowed it to be selected for further development. (C) 2011 Elsevier Ltd. All rights reserved.