(R)-1-[2-(4'-methanesulfonylbiphenyl-4-yl)ethyl]-2-methylpyrrolidine | 1021169-81-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (R)-1-[2-(4'-methanesulfonylbiphenyl-4-yl)ethyl]-2-methylpyrrolidine
• 英文别名: (R)-1-[2-(4'-Methanesulfonyl-biphenyl-4-yl)-ethyl]-2-methyl-pyrrolidine；(2R)-2-methyl-1-[2-[4-(4-methylsulfonylphenyl)phenyl]ethyl]pyrrolidine
• CAS: 1021169-81-2
• 化学式: C₂₀H₂₅NO₂S
• 分子量: 343.49
• InChiKey: WJQMVNBJCNFHHV-MRXNPFEDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  24
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  45.8
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (R)-1-[2-(4'-methanesulfonylbiphenyl-4-yl)ethyl]-2-methylpyrrolidine 在 盐酸 作用下， 以 甲醇 、 乙醚 为溶剂， 以0.07 g的产率得到(R)-1-[2-(4'-methanesulfonyl-biphenyl-4-yl)-ethyl]-2-methyl-pyrrolidine hydrochloride
  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：

  (R)-1-[2-(4-bromo-phenyl)-ethyl]-2-methyl-pyrrolidine 、 4-（甲磺酰基）苯硼酸 在 四(三苯基膦)钯 、 sodium carbonate 作用下， 以 乙醇 、 水 、 苯 为溶剂， 反应 0.5h， 生成 (R)-1-[2-(4'-methanesulfonylbiphenyl-4-yl)ethyl]-2-methylpyrrolidine
  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

文献信息

• [EN] METHODS AND COMPOUNDS USEFUL IN TREATING PRURITUS, AND METHODS FOR IDENTIFYING SUCH COMPOUNDS<br/>[FR] MÉTHODES ET COMPOSÉS UTILES POUR TRAITER LE PRURIT, ET PROCÉDÉS D'IDENTIFICATION DESDITS COMPOSÉS
  申请人：ARENA PHARM INC

  公开号：WO2013151982A1

  公开（公告）日：2013-10-10

  The present invention relates to methods of using histamine 3 receptor (H3R) antagonists to treat pruritus or itch in an individual and methods for using H3R to screen for compounds capable of treating pruritus in an individual and methods for using pruritus/itch model systems for screening H3R antagonists for their usefulness in treating pruritus.

  本发明涉及使用组胺3受体（H3R）拮抗剂治疗个体的瘙痒或瘙痒的方法，以及使用H3R筛选能够治疗个体瘙痒的化合物的方法，以及使用瘙痒/瘙痒模型系统筛选H3R拮抗剂以评估其在治疗瘙痒方面的有效性的方法。
• 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。
• [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.