N-[4-（3-吡啶基）苯基]-4-吗啉戊酰胺 | 874450-44-9

• 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
• 中文名称: N-[4-（3-吡啶基）苯基]-4-吗啉戊酰胺
• 英文名称: 5-(4-morpholinyl)-N-(4-(3-pyridyl)phenyl)pentanamide
• 英文别名: 5-morpholino-N-(4-(pyridin-3-yl)phenyl)pentanamide；SEN12333；WAY-317538；5-(morpholin-4-yl)pentanoic acid 4-(pyridin-3-yl)phenylamide；SEN12333/WAY-317538；5-(Morpholin-4-yl)-N-[4-(pyridin-3-yl)phenyl]pentanamide；5-morpholin-4-yl-N-(4-pyridin-3-ylphenyl)pentanamide
• CAS: 874450-44-9
• 化学式: C₂₀H₂₅N₃O₂
• 分子量: 339.437
• InChiKey: XCHIZTUBUXZESJ-UHFFFAOYSA-N

物化性质

• 溶解度：
  在 DMSO 中溶解度为 100 mM

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  25
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  54.5
• 氢给体数：
  1
• 氢受体数：
  4

安全信息

• 危险性防范说明：
  P261,P264,P270,P271,P280,P301+P312,P302+P352,P304+P340,P305+P351+P338,P330,P332+P313,P337+P313,P362,P403+P233,P405,P501
• 危险性描述：
  H302,H315,H319,H335
• 储存条件：
  室温密封，干燥

制备方法与用途

用途

SEN 12333 是一种烟碱乙酰胆碱受体（nAChR）激动剂。它在组胺 H3 受体上表现出功能拮抗作用（IC50 = 103 nM），并在人肾上腺素能 α3 nAChRs 上显示出较弱的激动剂活性（IC50 = 8.5 μM）。此外，SEN 12333 在小鼠模型中对 quisqualic 酸诱导的胆碱能退化具有神经保护作用，并且能够穿透脑部并在口服后被有效吸收。

反应信息

• 作为反应物：
  描述：

  N-[4-（3-吡啶基）苯基]-4-吗啉戊酰胺 在 叠氮基三甲基硅烷 、 五氯化磷 作用下， 以 二氯甲烷 为溶剂， 反应 18.0h， 生成 4-(4-(1-(4-(pyridin-3-yl)phenyl)-1H-tetrazol-5-yl)butyl)morpholine
  参考文献：
  名称：

  α7nAChR激动剂SEN12333类似物中酰胺键变化和联芳基修饰的研究

  摘要：

  实验几条证据支持α参与7胆碱受体在精神分裂症和老年痴呆症。α7nAChR的调节剂已被广泛审查与这些病理相关的认知功能障碍的治疗。SEN12333代表一种新型的α7nAChR激动剂化学型，具有减少副作用的潜力，但需要进一步的SAR探索。本工作研究了SEN12333的酰胺键，特别是其连接性和被四唑官能团（一种已知的顺式）取代酰胺等排。结果表明，SEN12333的原始酰胺键连接性有利于在α7nAChRs上的结合亲和力和激动剂活性。使用四唑等排物完全消除了亲和力和功能活性，并表明SEN12333以线性构象结合。本文报道的结果还表明SEN12333的末端芳族环内的吡啶氮对于结合亲和力或功能活性不是必需的。有必要对涉及操纵SEN12333中包含的其他部分的SAR进行进一步的调查。

  DOI：

  10.1016/j.ejmech.2014.07.029
• 作为产物：
  描述：

  5-溴戊酸 在 四(三苯基膦)钯 、 草酰氯 、 sodium carbonate 、 三乙胺 、 sodium iodide 作用下， 以 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 38.75h， 生成 N-[4-（3-吡啶基）苯基]-4-吗啉戊酰胺
  参考文献：
  名称：

  α7nAChR激动剂SEN12333类似物中酰胺键变化和联芳基修饰的研究

  摘要：

  实验几条证据支持α参与7胆碱受体在精神分裂症和老年痴呆症。α7nAChR的调节剂已被广泛审查与这些病理相关的认知功能障碍的治疗。SEN12333代表一种新型的α7nAChR激动剂化学型，具有减少副作用的潜力，但需要进一步的SAR探索。本工作研究了SEN12333的酰胺键，特别是其连接性和被四唑官能团（一种已知的顺式）取代酰胺等排。结果表明，SEN12333的原始酰胺键连接性有利于在α7nAChRs上的结合亲和力和激动剂活性。使用四唑等排物完全消除了亲和力和功能活性，并表明SEN12333以线性构象结合。本文报道的结果还表明SEN12333的末端芳族环内的吡啶氮对于结合亲和力或功能活性不是必需的。有必要对涉及操纵SEN12333中包含的其他部分的SAR进行进一步的调查。

  DOI：

  10.1016/j.ejmech.2014.07.029

文献信息

• ANTIPRURITIC AGENT
  申请人：Hayashi Kenichi

  公开号：US20140128606A1

  公开（公告）日：2014-05-08

  An antipruritic which exerts an antipruritic effect based on a novel action mechanism and is effective for pruritus. The antipruritic contains as an effective ingredient a compound which activates a central type nicotinic acetylcholine receptor.

  一种抗瘙痒药物，基于新颖的作用机制发挥抗瘙痒作用，并对瘙痒有效。该抗瘙痒药物含有一种有效成分，该成分可以激活中枢型尼古丁乙酰胆碱受体。
• Modulators or Alpha7 Nicotinic Acetylcholine Receptors and Therapeutic Uses Thereof
  申请人：Gaviraghi Giovanni

  公开号：US20080275028A1

  公开（公告）日：2008-11-06

  The present invention relates to compounds with α7 nAChR agonistic activity, processes for their preparation, pharmaceutical compositions containing the same and the use thereof for the treatment of neurological, psychiatric, cognitive, immunological and inflammatory disorders.

  本发明涉及具有α7 nAChR激动活性的化合物，其制备方法，含有该化合物的制药组合物以及用于治疗神经、精神、认知、免疫和炎症性疾病的用途。
• SAR and biological evaluation of SEN12333/WAY-317538: Novel alpha 7 nicotinic acetylcholine receptor agonist
  作者：Simon N. Haydar、Chiara Ghiron、Laura Bettinetti、Hendrick Bothmann、Thomas A. Comery、John Dunlop、Salvatore La Rosa、Iolanda Micco、Martina Pollastrini、Joanna Quinn、Renza Roncarati、Carla Scali、Michela Valacchi、Maurizio Varrone、Riccardo Zanaletti

  DOI：10.1016/j.bmc.2009.05.040

  日期：2009.7

  Alpha 7 nicotinic acetylcholine receptor (alpha(7) nAChR) agonists are promising therapeutic candidates for the treatment of cognitive impairment associated with a variety of disorders including Alzheimer's disease and schizophrenia. Alpha 7 nAChRs are expressed in brain regions associated with cognitive function, regulate cholinergic neurotransmission and have been shown to be down regulated in both schizophrenia and Alzheimer's disease. Herein we report a novel, potent small molecule agonist of the alpha 7 nAChR, SEN12333/WAY-317538. This compound is a selective agonist of the alpha(7) nAChR with excellent in vitro and in vivo profiles, excellent brain penetration and oral bioavailability, and demonstrates in vivo efficacy in multiple behavioural cognition models. The SAR and biological evaluation of this series of compounds are discussed. (C) 2009 Elsevier Ltd. All rights reserved.
• 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.
• Consequences of linker length alteration of the α7 nicotinic acetylcholine receptor (nAChR) agonist, SEN12333
  作者：Corinne Beinat、Samuel D. Banister、Saundra van Prehn、Munikumar Reddy Doddareddy、David Hibbs、Michael Sako、Mary Chebib、Thao Tran、Nour Al-Muhtasib、Yingxian Xiao、Michael Kassiou

  DOI：10.1016/j.bmcl.2012.02.052

  日期：2012.4

  A series of ligands based on SEN12333, containing either contracted or elongated alkyl chains, were synthesized and evaluated in molecular docking studies against a homology model of the alpha 7 nicotinic acetylcholine receptor (nAChR) subtype. The predicted binding of all ligands was highly similar, with the exception of the analog containing a 5 methylene unit spacer. However, in vitro competition binding assays revealed that the ligands possessed dissimilar binding affinities, with a K-i range of more than an order of magnitude (K-i = 0.50 to >10 mu M), and only SEN12333 itself exhibited functional activity at the alpha 7 nAChR. (C) 2012 Elsevier Ltd. All rights reserved.