1-(4-bromophenylsulfonyl)-4-methoxypiperidine | 1001334-58-2

• 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: 1-(4-bromophenylsulfonyl)-4-methoxypiperidine
• 英文别名: 1-((4-Bromophenyl)sulfonyl)-4-methoxypiperidine；1-(4-bromophenyl)sulfonyl-4-methoxypiperidine
• CAS: 1001334-58-2
• 化学式: C₁₂H₁₆BrNO₃S
• mdl: MFCD12515963
• 分子量: 334.234
• InChiKey: KDZXGIAEBRRWQF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  18
• 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：
  55
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-(4-bromophenylsulfonyl)-4-methoxypiperidine 在 N-羟基-7-氮杂苯并三氮唑 、 2,2,6,6-四甲基-3,5-庚二酮 、 caesium carbonate 、 N,N-二异丙基乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 、 copper(I) bromide 、 lithium hydroxide 作用下， 以 四氢呋喃 、 N-甲基吡咯烷酮 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.5h， 生成 3-(4-((4-methoxypiperidin-1-yl)sulfonyl)phenoxy)-N-(1-methyl-1H-pyrazol-3-yl)-5-((3-methylbut-2-en-1-yl)oxy)benzamide
  参考文献：
  名称：

  Design, synthesis, and pharmacological evaluation of benzamide derivatives as glucokinase activators

  摘要：

  A series of benzamide derivatives were assembled by using the privileged-fragment-merging (PFM) strategy and their SAR studies as glucokinase activators were described. Compounds 5 and 16b were identified having a suitable balance of potency and activation profile. They showed EC50 values of 28.3 and 44.8 nM, and activation folds of 2.4 and 2.2, respectively. However, both compounds displayed a minor reduction in plasma glucose levels on imprinting control region (ICR) mice. Unfavorable pharmacokinetic profiles (PK) were also observed on these two compounds. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.03.008
• 作为产物：
  描述：

  4-甲氧基哌啶 、 4-溴苯磺酰氯 在 吡啶 作用下， 以 二氯甲烷 为溶剂， 反应 4.0h， 生成 1-(4-bromophenylsulfonyl)-4-methoxypiperidine
  参考文献：
  名称：

  Design, synthesis, and pharmacological evaluation of benzamide derivatives as glucokinase activators

  摘要：

  A series of benzamide derivatives were assembled by using the privileged-fragment-merging (PFM) strategy and their SAR studies as glucokinase activators were described. Compounds 5 and 16b were identified having a suitable balance of potency and activation profile. They showed EC50 values of 28.3 and 44.8 nM, and activation folds of 2.4 and 2.2, respectively. However, both compounds displayed a minor reduction in plasma glucose levels on imprinting control region (ICR) mice. Unfavorable pharmacokinetic profiles (PK) were also observed on these two compounds. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.03.008

文献信息

• Design and Evaluation of Novel Biphenyl Sulfonamide Derivatives with Potent Histamine H₃ Receptor Inverse Agonist Activity
  作者：Jonathan A. Covel、Vincent J. Santora、Jeffrey M. Smith、Rena Hayashi、Charlemagne Gallardo、Michael I. Weinhouse、Jason B. Ibarra、Jeffrey A. Schultz、Douglas M. Park、Scott A. Estrada、Brian J. Hofilena、Michelle D. Pulley、Brian M. Smith、Albert Ren、Marissa Suarez、John Frazer、Jeffrey Edwards、Erin K. Hauser、Jodie Lorea、Graeme Semple、Andrew J. Grottick

  DOI：10.1021/jm900857n

  日期：2009.9.24

  Phenethyl-R-2-methylpyrrolidine containing biphenylsulfonamide compounds were shown to be potent and selective antagonists of the H3 receptor. Several of these compounds demonstrated in vivo activity in a rat model of (R)-α-methyl histamine (RAMH) induced dipsogenia, and one compound (4e) provided an increase in wakefulness in rats as measured by polysomnographic methods. However, more detailed analysis of the PK/PD

  组胺-H 3受体的拮抗作用是探索增加清醒性以治疗诸如过度日间嗜睡（EDS）以及其他睡眠或认知障碍之类的疾病的一种策略。含有苯乙基-R -2-甲基吡咯烷的联苯磺酰胺化合物被证明是H 3受体的有效和选择性拮抗剂。这些化合物中的几种在（R）-α-甲基组胺（RAMH）诱导的成瘾症的大鼠模型中具有体内活性，一种化合物（4e）通过多导睡眠监测法测量了大鼠的清醒度。但是，对PK / PD关系的更详细分析表明存在共同的活性代谢物，这可能会使该系列化合物无法进一步开发。
• MODULATORS OF THE HISTAMINE H3-RECEPTOR USEFUL FOR THE TREATMENT OF DISORDERS RELATED THERETO
  申请人：Arena Pharmaceuticals, Inc.

  公开号：EP2035372A1

  公开（公告）日：2009-03-18
• [EN] MODULATORS OF THE HISTAMINE H3-RECEPTOR USEFUL FOR THE TREATMENT OF DISORDERS RELATED THERETO<br/>[FR] MODULATEURS DU RÉCEPTEUR H3 DE L'HISTAMINE UTILES DANS LE TRAITEMENT DE TROUBLES LIÉS AUDIT RÉCEPTEUR
  申请人：ARENA PHARM INC

  公开号：WO2008005338A1

  公开（公告）日：2008-01-10

  [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 and pharmaceutical compositions thereof are directed to methods useful in the treatment of histamine H3-receptor associated disorders, such as, cognitive disorders, epilepsy, brain trauma, depression, obesity, disorders of sleep and wakefulness such as narcolepsy, 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 biphényl-sulfonamides selon la formule (Ia) et leurs compositions pharmaceutiques qui modulent l'activité du récepteur H3 de l'histamine. Les composés et les compositions pharmaceutiques les contenant sont destinés à des procédés utiles dans le traitement de troubles associés au récepteur H3 de l'histamine, tels que les troubles cognitifs, l'épilepsie, les traumatismes crâniens, la dépression, l'obésité, les troubles de la veille et du sommeil tels que la narcolepsie, l'hypersomnie, le syndrome de somnolence, le syndrome de décalage horaire, l'apnée du sommeil et similaires, l'hyperactivité avec déficit de l'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 similaires.
• Design, synthesis, and pharmacological evaluation of benzamide derivatives as glucokinase activators
  作者：Weiwei Mao、Mengmeng Ning、Zhiqing Liu、Qingzhang Zhu、Ying Leng、Ao Zhang

  DOI：10.1016/j.bmc.2012.03.008

  日期：2012.5

  A series of benzamide derivatives were assembled by using the privileged-fragment-merging (PFM) strategy and their SAR studies as glucokinase activators were described. Compounds 5 and 16b were identified having a suitable balance of potency and activation profile. They showed EC50 values of 28.3 and 44.8 nM, and activation folds of 2.4 and 2.2, respectively. However, both compounds displayed a minor reduction in plasma glucose levels on imprinting control region (ICR) mice. Unfavorable pharmacokinetic profiles (PK) were also observed on these two compounds. (C) 2012 Elsevier Ltd. All rights reserved.