N-[3-[4-[4-[(环己基甲基磺酰基)氨基]丁基]哌嗪-1-基]苯基]乙酰胺 | 740873-06-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 中文名称: N-[3-[4-[4-[(环己基甲基磺酰基)氨基]丁基]哌嗪-1-基]苯基]乙酰胺
• 英文名称: Naluzotan
• 英文别名: N-{3-[4-(4-cyclohexylmethanesulfonylaminobutyl)piperazin-1-yl]phenyl}acetamide；N-[3-[4-[4-(cyclohexylmethylsulfonylamino)butyl]piperazin-1-yl]phenyl]acetamide
• CAS: 740873-06-7
• 化学式: C₂₃H₃₈N₄O₃S
• 分子量: 450.646
• InChiKey: SPWZXWDPAWDKQE-UHFFFAOYSA-N

物化性质

• 密度：
  1.169
• 溶解度：
  溶于二甲基亚砜

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  31
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.7
• 拓扑面积：
  90.1
• 氢给体数：
  2
• 氢受体数：
  6

安全信息

• 储存条件：
  2-8℃

制备方法与用途

Naluzotan 是一种新颖且有效的选择性 5-HT1A 激动剂，其 IC50 和 Ki 值分别为约 20 nM 和 5.1 nM；同时它也是 hERG K+ 通道阻滞剂，IC50 值为 3800 nM。Naluzotan 常用于治疗焦虑和抑郁症。

反应信息

• 作为反应物：
  描述：

  N-[3-[4-[4-[(环己基甲基磺酰基)氨基]丁基]哌嗪-1-基]苯基]乙酰胺 在 盐酸 作用下， 以 乙醚 为溶剂， 生成 N-{3-[4-(4-cyclohexylmethanesulfonylaminobutyl)piperazin-1-yl]phenyl}acetamide HCl
  参考文献：
  名称：

  [EN] NEW ARYLPIPERAZINYL COMPOUNDS
  [FR] NOUVEAUX COMPOSES D'ARYLPIPERAZINYLE

  摘要：

  公开号：

  WO2004069794A3
• 作为产物：
  描述：

  C-cyclohexyl-N-{4-[4-(3-nitrophenyl)piperazin-1-yl]butyl}methanesulfonamide 在 盐酸 、 三乙胺 、 tin(ll) chloride 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 0.5h， 生成 N-[3-[4-[4-[(环己基甲基磺酰基)氨基]丁基]哌嗪-1-基]苯基]乙酰胺
  参考文献：
  名称：

  An Integrated in Silico 3D Model-Driven Discovery of a Novel, Potent, and Selective Amidosulfonamide 5-HT_1A Agonist (PRX-00023) for the Treatment of Anxiety and Depression

  摘要：

  We report the discovery of a novel, potent, and selective amidosulfonamide nonazapirone 5-HT1A agonist for the treatment of anxiety and depression, which is now in Phase III clinical trials for generalized anxiety disorder (GAD). The discovery of 20m (PRX-00023), N-{3-[4-(4-cyclohexylmethanesulfonylaminobutyl)piperazin-1-yl] phenyl} acetamide, and its backup compounds, followed a new paradigm, driving the entire discovery process with in silico methods and seamlessly integrating computational chemistry with medicinal chemistry, which led to a very rapid discovery timeline. The program reached clinical trials within less than 2 years from initiation, spending less than 6 months in lead optimization with only 31 compounds synthesized. In this paper we detail the entire discovery process, which started with modeling the 3D structure of 5-HT1A using the PREDICT methodology, and then performing in silico screening on that structure leading to the discovery of a 1 nM lead compound (8). The lead compound was optimized following a strategy devised based on in silico 3D models and realized through an in silico-driven optimization process, rapidly overcoming selectivity issues (affinity to 5-HT1A vs alpha(1)-adrenergic receptor) and potential cardiovascular issues (hERG binding), leading to a clinical compound. Finally we report key in vivo preclinical and Phase I clinical data for 20m tolerability, pharmacokinetics, and pharmacodynamics and show that these favorable results are a direct outcome of the properties that were ascribed to the compound during the rational structure-based discovery process. We believe that this is one of the first examples for a Phase III drug candidate that was discovered and optimized, from start to finish, using in silico model-based methods as the primary tool.

  DOI：

  10.1021/jm0508641

文献信息

• Arylpiperazinyl compounds
  申请人：——

  公开号：US20040220192A1

  公开（公告）日：2004-11-04

  The invention relates to 5-HT receptor agonists or antagonists. Novel arylpiperazinyl sulfonamide compounds represented by Formula I, and synthesis and uses thereof for treating diseases including those mediated directly or indirectly by 5-HT receptors, are disclosed. Such conditions include central nervous system disorders such as generalized anxiety disorder, ADD/ADHD, neural injury, stroke, and migraine. Methods of preparation and novel intermediates and pharmaceutical salts thereof are also included.

  该发明涉及5-HT受体激动剂或拮抗剂。公开了由公式I表示的新型芳基哌嗪磺酰胺化合物及其合成和用于治疗直接或间接由5-HT受体介导的疾病的用途。这些疾病包括中枢神经系统疾病，如广泛性焦虑症、ADD/ADHD、神经损伤、中风和偏头痛。还包括制备方法、新型中间体和其制药盐。
• Arylpiperazinyl Compounds
  申请人：Dhanoa S. Dale

  公开号：US20080027066A1

  公开（公告）日：2008-01-31

  The invention relates to 5-HT receptor agonists or antagonists. Novel arylpiperazinyl sulfonamide compounds represented by Formula I, and synthesis and uses thereof for treating diseases including those mediated directly or indirectly by 5-HT receptors, are disclosed. Such conditions include central nervous system disorders such as generalized anxiety disorder, ADD/ADHD, neural injury, stroke, and migraine. Methods of preparation and novel intermediates and pharmaceutical salts thereof are also included.

  该发明涉及5-HT受体激动剂或拮抗剂。公开了由式I表示的新型芳基哌嗪磺酰胺化合物及其合成和用途，用于治疗包括直接或间接通过5-HT受体介导的疾病。这些疾病包括中枢神经系统疾病，如广泛性焦虑症，ADD / ADHD，神经损伤，中风和偏头痛。还包括制备方法、新型中间体和药物盐。
• NEUROGENESIS BY MUSCARINIC RECEPTOR MODULATION
  申请人：Barlow Carrolee

  公开号：US20070049576A1

  公开（公告）日：2007-03-01

  The instant disclosure describes methods for treating diseases and conditions of the central and peripheral nervous system by stimulating or increasing neurogenesis. The disclosure includes compositions and methods based on muscarinic receptor modulation, such as via inhibition of acetylcholine esterase (AChE) activity, alone or in combination with another neurogenic agent to stimulate or activate the formation of new nerve cells.

  该即时披露描述了通过刺激或增加神经发生来治疗中枢神经系统和外周神经系统的疾病和病症的方法。该披露包括基于毒蕈碱受体调节的组合物和方法，例如通过抑制乙酰胆碱酯酶（AChE）活性，单独或与另一种神经生成剂结合以刺激或激活新神经细胞的形成。
• Neurogenesis by muscarinic receptor modulation with sabcomelin
  申请人：Braincells, Inc.

  公开号：EP2258359A2

  公开（公告）日：2010-12-08

  The instant disclosure describes methods for treating diseases and conditions of the central and peripheral nervous system by stimulating or increasing neurogenesis. The disclosure includes compositions and methods based on muscarinic receptor modulation, such as via inhibition of acetylcholine esterase (AChE) activity, alone or in combination with another neurogenic agent to stimulate or activate the formation of new nerve cells.

  本公开描述了通过刺激或增加神经发生来治疗中枢和周围神经系统疾病和病症的方法。本公开包括基于毒蕈碱受体调节的组合物和方法，例如通过抑制乙酰胆碱酯酶（AChE）活性，单独或与另一种神经发生剂联合使用，以刺激或激活新神经细胞的形成。
• Neurogenesis by muscarinic receptor modulation
  申请人：Braincells, Inc.

  公开号：EP2275095A2

  公开（公告）日：2011-01-19

  The instant disclosure describes methods for treating diseases and conditions of the central and peripheral nervous system by stimulating or increasing neurogenesis. The disclosure includes compositions and methods based on muscarinic receptor modulation, such as via inhibition of acetylcholine esterase (AChE) activity, alone or in combination with another neurogenic agent to stimulate or activate the formation of new nerve cells.

  本公开描述了通过刺激或增加神经发生来治疗中枢和周围神经系统疾病和病症的方法。本公开包括基于毒蕈碱受体调节的组合物和方法，例如通过抑制乙酰胆碱酯酶（AChE）活性，单独或与另一种神经发生剂联合使用，以刺激或激活新神经细胞的形成。