6-bromo-N-(4-cyanophenylmethyl)hexanamide | 1052148-20-5

• 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: 6-bromo-N-(4-cyanophenylmethyl)hexanamide
• 英文别名: 6-bromo-N-[(4-cyanophenyl)methyl]hexanamide
• CAS: 1052148-20-5
• 化学式: C₁₄H₁₇BrN₂O
• 分子量: 309.206
• InChiKey: PQFYIDGUCQZAQK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  18
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  52.9
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  6-bromo-N-(4-cyanophenylmethyl)hexanamide 、 1-([1,1'-biphenyl]-2-yl)piperazine 在 potassium carbonate 作用下， 以 乙腈 为溶剂， 以90%的产率得到LP-211
  参考文献：
  名称：

  Structural Modifications of N-(1,2,3,4-Tetrahydronaphthalen-1-yl)-4-Aryl-1-piperazinehexanamides: Influence on Lipophilicity and 5-HT₇ Receptor Activity. Part III

  摘要：

  Starting from the previously reported 5-HT7 receptor agents 4-7 with N-(1,2,3,4-tetrahydronaphthalen-1-yl)-4-aryl-1-piperazinehexanamide structure, the 1-(2-methylthiophenyl)-, 1-(2-diphenyl)-, 1-(2-isopropylphenyl)-, and 1-(2-methoxyphenyl)piperazine derivatives 8-31 were designed with the primary aim to obtain new compounds endowed with suitable physicochemical properties for rapid and extensive penetration into the brain. The affinities for 5-HT7, 5-HT1A, and D-2 receptors of compounds 8-31 were assessed, and several compounds displayed 5-HT7 receptor affinities in the nanomolar range. Among these, N-(4-cyanophenylmethyl)-4-(2-diphenyl)-1-piperazinehexanamide (25) showed high 5-HT7 receptor affinity (K-i = 0.58 nM), high selectivity over 5-HT1A and D-2 receptors (324- and 245-fold, respectively), and agonist properties (maximal effect = 82%, EC50 = 0.60 mu M). After intraperitoneal injection in mice, 25 rapidly reached the systemic circulation and entered the brain. Its brain concentration-time profile paralleled that in plasma, indicating that 25 rapidly and freely distributes across the blood-brain barrier. Compound 25 underwent N-dealkylation to the corresponding 1-arylpiperazine metabolite.

  DOI：

  10.1021/jm800615e
• 作为产物：
  描述：

  6-溴己酰氯 、 对氰基苄胺 在 sodium hydroxide 作用下， 以 二氯甲烷 、 水 为溶剂， 生成 6-bromo-N-(4-cyanophenylmethyl)hexanamide
  参考文献：
  名称：

  5-羟色胺5-HT 7受体激动剂N-（4-氰基苯基甲基）-4-（2-联苯基）-1-哌嗪己酰胺（LP-211）的结构修饰，以改善体外微粒体的稳定性：案例研究

  摘要：

  5-HT 7血清素受体正在揭示神经发育和神经精神疾病的创新治疗策略的有希望的目标。在这里，我们报告选择性和脑渗透5-HT 7受体激动剂LP-211（1）的三十个长链芳基哌嗪类似物的合成，旨在增强对微粒体氧化代谢的稳定性。使用了常用的药物化学策略（例如，降低了整体的亲脂性，引入了吸电子基团，阻断了可能的新陈代谢易位部位）和体外测试了微粒体的稳定性。数据表明，采用的设计策略不会直接转化为稳定性的提高。相反，化合物的代谢稳定性与在分子的明确定义的区域中特定取代基的存在有关。收集的数据允许构建机器学习模型，该模型在给定的化学空间内能够描述和定量预测化合物的代谢稳定性。大部分的合成的化合物的保持高亲和性对5-HT 7种受体，并显示向选择性5-HT 6和多巴胺d 2个受体和不同的选择性5-HT 1A和α 1个肾上腺素能受体。化合物50表现出比1高3倍的体外抗氧化代谢稳定性，并且能够通过5-HT 7受体

  DOI：

  10.1016/j.ejmech.2016.05.005

文献信息

• Synthesis of piperazino-substituted benzo[b]furans as potential CNS agents
  作者：Jeff Klenc、Lucjan Strekowski

  DOI：10.1515/hc.2010.009

  日期：2010.1.1

  The synthesis of a series of substituted benzofurans is reported. Selected compounds have been shown to bind strongly and with high selectivity to the serotonin receptor 5-HT2A in the presence of the receptor 5-HT7 in vitro.
• Structural modifications of the serotonin 5-HT7 receptor agonist N-(4-cyanophenylmethyl)-4-(2-biphenyl)-1-piperazinehexanamide (LP-211) to improve in vitro microsomal stability: A case study
  作者：Enza Lacivita、Sabina Podlewska、Luisa Speranza、Mauro Niso、Grzegorz Satała、Roberto Perrone、Carla Perrone-Capano、Andrzej J. Bojarski、Marcello Leopoldo

  DOI：10.1016/j.ejmech.2016.05.005

  日期：2016.9

  and α1 adrenergic receptors. Compound 50 showed 3-fold higher in vitro stability towards oxidative metabolism than 1 and was able to stimulate neurite outgrowth in neuronal primary cultures through the 5-HT7 receptor in a shorter time and at a lower concentration than the agonist 1. A preliminary disposition study in mice revealed that compound 50 was metabolically stable and was able to pass the blood–brain

  5-HT 7血清素受体正在揭示神经发育和神经精神疾病的创新治疗策略的有希望的目标。在这里，我们报告选择性和脑渗透5-HT 7受体激动剂LP-211（1）的三十个长链芳基哌嗪类似物的合成，旨在增强对微粒体氧化代谢的稳定性。使用了常用的药物化学策略（例如，降低了整体的亲脂性，引入了吸电子基团，阻断了可能的新陈代谢易位部位）和体外测试了微粒体的稳定性。数据表明，采用的设计策略不会直接转化为稳定性的提高。相反，化合物的代谢稳定性与在分子的明确定义的区域中特定取代基的存在有关。收集的数据允许构建机器学习模型，该模型在给定的化学空间内能够描述和定量预测化合物的代谢稳定性。大部分的合成的化合物的保持高亲和性对5-HT 7种受体，并显示向选择性5-HT 6和多巴胺d 2个受体和不同的选择性5-HT 1A和α 1个肾上腺素能受体。化合物50表现出比1高3倍的体外抗氧化代谢稳定性，并且能够通过5-HT 7受体
• Structural Modifications of <i>N</i>-(1,2,3,4-Tetrahydronaphthalen-1-yl)-4-Aryl-1-piperazinehexanamides: Influence on Lipophilicity and 5-HT₇ Receptor Activity. Part III
  作者：Marcello Leopoldo、Enza Lacivita、Paola De Giorgio、Claudia Fracasso、Sara Guzzetti、Silvio Caccia、Marialessandra Contino、Nicola A. Colabufo、Francesco Berardi、Roberto Perrone

  DOI：10.1021/jm800615e

  日期：2008.9.25

  Starting from the previously reported 5-HT7 receptor agents 4-7 with N-(1,2,3,4-tetrahydronaphthalen-1-yl)-4-aryl-1-piperazinehexanamide structure, the 1-(2-methylthiophenyl)-, 1-(2-diphenyl)-, 1-(2-isopropylphenyl)-, and 1-(2-methoxyphenyl)piperazine derivatives 8-31 were designed with the primary aim to obtain new compounds endowed with suitable physicochemical properties for rapid and extensive penetration into the brain. The affinities for 5-HT7, 5-HT1A, and D-2 receptors of compounds 8-31 were assessed, and several compounds displayed 5-HT7 receptor affinities in the nanomolar range. Among these, N-(4-cyanophenylmethyl)-4-(2-diphenyl)-1-piperazinehexanamide (25) showed high 5-HT7 receptor affinity (K-i = 0.58 nM), high selectivity over 5-HT1A and D-2 receptors (324- and 245-fold, respectively), and agonist properties (maximal effect = 82%, EC50 = 0.60 mu M). After intraperitoneal injection in mice, 25 rapidly reached the systemic circulation and entered the brain. Its brain concentration-time profile paralleled that in plasma, indicating that 25 rapidly and freely distributes across the blood-brain barrier. Compound 25 underwent N-dealkylation to the corresponding 1-arylpiperazine metabolite.