2-溴-N-[2-(7-甲氧基萘-1-基)乙基]乙酰胺 | 138112-84-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 中文名称: 2-溴-N-[2-(7-甲氧基萘-1-基)乙基]乙酰胺
• 英文名称: S 20251
• 英文别名: N-[2-(7-methoxynaphth-1-yl)ethyl]bromoacetamide；2-bromo-N-(2-(7-methoxynaphthalen-1-yl)ethyl)acetamide；bromoacetamidoagomelatine；N-[2-(7-methoxynaphth-1-yl)ethyl)-2-bromoacetamide；Acetamide, 2-bromo-N-(2-(7-methoxy-1-naphthalenyl)ethyl)-；2-bromo-N-[2-(7-methoxynaphthalen-1-yl)ethyl]acetamide
• CAS: 138112-84-2
• 化学式: C₁₅H₁₆BrNO₂
• 分子量: 322.202
• InChiKey: HRZANPMSVAGALW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  19
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  38.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-溴-N-[2-(7-甲氧基萘-1-基)乙基]乙酰胺 在 palladium 10% on activated carbon 、 氢气 、 三乙胺 作用下， 以 甲醇 、 丙酮 为溶剂， 20.0 ℃ 、101.33 kPa 条件下， 反应 13.0h， 生成 N-[2-(7-methoxy-naphthalen-1-yl)ethyl]-2-(methylamino)acetamide hydrochloride
  参考文献：
  名称：

  Design, synthesis and pharmacological evaluation of new series of naphthalenic analogues as melatoninergic (MT1/MT2) and serotoninergic 5-HT2C dual ligands (I)

  摘要：

  As part of our ongoing interest in developing new melatoninergic ligands bearing the same pharmacological profile as agomelatine, we focused our attention on this compound as a lead. Several chemical modifications have been performed on positions C-3 and 8 of the naphthalene ring determined as primary targets for the agomelatine metabolism. Herein we report the modulation of the positions C-3 and 7 in addition of the amide side chain because of this later prominent role in the affinity profile of such ligands. Synthesized compounds were then biologically evaluated at human cloned melatoninergic and serotoninergic receptors and showed different binding affinity and intrinsic activity profiles. Compounds bearing fluoroacetamide group (compounds 4 and 5) showed a high melatoninergic binding affinity particularly towards MT1 receptor subtype. Thus, the fluoroacetamide 4 exhibited a good melatoninergic (mT(1)/MT2) binding affinity (70 pm) higher than the lead. Moreover, other compounds (10a, 10e, 16, 17 and 18) issued from these modulations behaved as MT1 and MT2 agonists and exhibited a sub-nanomolar binding affinity towards these receptors. However, only compounds 10e, 17 and 18 showed a sub-nanomolar binding affinity at 5-HT2C higher than the agomelatine. (C) 2012 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2012.01.027
• 作为产物：
  描述：

  溴乙酰氯 、 2-(7-甲氧基萘-1-基)乙胺盐酸盐 在 potassium carbonate 作用下， 以 氯仿 、 水 为溶剂， 反应 0.5h， 以93%的产率得到2-溴-N-[2-(7-甲氧基萘-1-基)乙基]乙酰胺
  参考文献：
  名称：

  新型萘和生物等排相关酰胺衍生物作为褪黑激素受体配体的合成和构效关系。

  摘要：

  合成了一系列 N-萘乙基酰胺衍生物并作为褪黑激素受体配体进行了评估。每种化合物对褪黑激素受体的亲和力通过使用[2-125I]碘褪黑激素对绵羊结节膜匀浆的结合研究来确定。构效关系得出结论，萘是褪黑激素吲哚部分的生物等排体。此外，似乎亲和力受到酰胺官能团氮的取代基大小的强烈影响。许多这些配体给出了双相剂量反应曲线，这表明绵羊结节细胞内可能存在两种褪黑激素受体亚型。用苯并呋喃或苯并噻吩代替萘并没有强烈改变对褪黑激素受体的亲和力。相比之下，苯并咪唑类似物是一种较差的配体。化合物 7，褪黑激素的萘类似物，褪黑激素受体的选择性配体和激动剂衍生物，已被选择用于临床开发。

  DOI：

  10.1021/jm00046a006

文献信息

• Compounds having a naphthalene structure
  申请人：Adir et Compagnie

  公开号：US05194614A1

  公开（公告）日：1993-03-16

  Compounds of general formula: ##STR1## in which A and R are defined in the description.

  通式为：##STR1##，其中A和R在描述中有定义。
• N-[2-(7-lower-alkoxynaphth-1-yl)ethyl]benzamides
  申请人：Adir et Compagnie

  公开号：US05318994A1

  公开（公告）日：1994-06-07

  Compounds of the formula: ##STR1## in which: A represents ##STR2## R represents linear or branched lower alkyl, R.sub.1 represents hydrogen or linear or branched lower alkyl, and R.sub.2 represents aryl or lower arylalkyl or aryl or lower arylalkyl substituted by lower alkyl, lower alkoxy, trifluoromethyl, or halogen, aryl means phenyl or naphthyl, as well as optical isomers, epimers and diastereoisomers and addition salts thereof with a pharmaceutically-acceptable acid, lower alkyl and lower alkoxy having 1 to 6 carbon atoms inclusive, and medicaments containing the same which are useful for the treatment of disorders of the melatoninergic system.

  分子式为：##STR1## 其中：A代表##STR2##，R代表线性或支链低碳基，R.sub.1代表氢或线性或支链低碳基，R.sub.2代表芳基或低芳基烷基或被低碳基，低烷氧基，三氟甲基或卤素取代的芳基或低芳基烷基取代的芳基，芳基表示苯基或萘基，以及光学异构体，外消旋异构体和二对映异构体及其与药学上可接受的酸的加合物，其中低碳基和低烷氧基具有1到6个碳原子，以及包含它们的药物，用于治疗褪黑素系统的疾病。
• Radiosynthesis and <i>In Vivo</i> Evaluation of Four Positron Emission Tomography Tracer Candidates for Imaging of Melatonin Receptors
  作者：Hussein Bdair、Thomas A. Singleton、Karen Ross、Dean Jolly、Min Su Kang、Arturo Aliaga、Marius Tuznik、Tanpreet Kaur、Saïd Yous、Jean-Paul Soucy、Gassan Massarweh、Peter J. H. Scott、Robert Koeppe、Gilberto Spadoni、Annalida Bedini、David A. Rudko、Gabriella Gobbi、Chawki Benkelfat、Pedro Rosa-Neto、Allen F. Brooks、Alexey Kostikov

  DOI：10.1021/acschemneuro.1c00678

  日期：2022.5.4

  therapeutic target for new pharmacological interventions in the treatment of sleep and mood disorders; thus, imaging tools to further investigate its role in the brain are highly sought-after. We aimed to develop selective radiotracers for in vivo imaging of both MT1 and MT2 by positron emission tomography (PET). We identified four previously reported MT ligands with picomolar affinities to the target based

  褪黑激素是一种神经激素，通过激活褪黑激素受体 1 型和 2 型（MT 1和 MT 2）来调节哺乳动物的多种生理功能。褪黑激素能系统是治疗睡眠和情绪障碍的新药理学干预的新兴治疗靶点；因此，进一步研究其在大脑中作用的成像工具非常受欢迎。我们的目标是开发选择性放射性示踪剂，用于通过正电子发射断层扫描 (PET)对 MT 1和 MT 2进行体内成像。我们根据不同的支架鉴定了四种先前报道的对靶标具有皮摩尔亲和力的 MT 配体，这些支架也适用于碳 11 或氟 18 的放射性标记。[11 C]UCM765、[ 11 C]UCM1014、[ 18 F]3-fluoroagomelatine ([ 18 F]3FAGM) 和 [ 18 F]fluoroacetamidoagomelatine ([ 18 F]FAAGM) 以高放射化学纯度合成并在野外进行了评估型大鼠。所有四种示踪剂在大鼠中显示出中等至高的脑
• Neu; Niles; Brough, Medicinal Chemistry Research, 2000, vol. 10, # 2, p. 114 - 121
  作者：Neu、Niles、Brough、Chen、Snieckus、Firnau

  DOI：——

  日期：——
• Nouveaux dérivés à structure naphtalénique, leur procédé de préparation et les compositions pharmaceutiques qui les contiennent
  申请人：ADIR ET COMPAGNIE

  公开号：EP0447285B1

  公开（公告）日：1993-05-12