N-[2-(3-bromo-7-methoxynaphth-1-yl)ethyl]acetamide | 686319-38-0

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: N-[2-(3-bromo-7-methoxynaphth-1-yl)ethyl]acetamide
• 英文别名: N-(2-(3-bromo-7-methoxynaphthalen-1-yl)ethyl)acetamide；N-(2-(7-methoxy-3-bromonaphthalen-1-yl)ethyl)acetamide；3-bromoagomelatine；N-[2-(3-bromo-7-methoxy-1-naphthyl)ethyl]acetamide；N-[2-(3-Bromo-7-methoxynaphthalen-1-yl)ethyl]acetamide
• CAS: 686319-38-0
• 化学式: C₁₅H₁₆BrNO₂
• 分子量: 322.202
• InChiKey: DALDAAWMVJDLJA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  19
• 可旋转键数：
  4
• 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：

  N-[2-(3-bromo-7-methoxynaphth-1-yl)ethyl]acetamide 在 吡啶 、 sodium periodate 、 四氧化锇 、 四(三苯基膦)钯 、 盐酸羟胺 、 氨 、 氢气 作用下， 以 四氢呋喃 、 甲醇 、 水 、 甲苯 为溶剂， 20.0~100.0 ℃ 、2.0 MPa 条件下， 反应 80.0h， 生成 N-[2-(3-aminomethyl-7-methoxynaphthalen-1-yl)ethyl]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：

  阿戈美拉汀 在 溴 作用下， 以 溶剂黄146 为溶剂， 反应 6.0h， 以73%的产率得到N-[2-(3-bromo-7-methoxynaphth-1-yl)ethyl]acetamide
  参考文献：
  名称：

  设计和合成3-苯基四氢萘衍生物作为新的选择性MT 2褪黑素能配体。第二部分

  摘要：

  在对褪黑素能受体进行研究之后，我们开发了褪黑素的新四氢萘衍生物，这些衍生物已作为选择性褪黑素受体配体进行了测试。关于苯基取代基获得选择性配体的作用，通过修饰酰基和苯环上的取代来实现选择性和活性的调节。在17种评估的衍生物中，有10种具有与褪黑激素相似的MT 2受体亲和力。此外，我们已经实现了超过MT 1的MT 2选择性（选择性> 100），并且能够进一步扩展四氢邻苯二甲酸系列的RSA。但是，此处提供的化合物显示出部分激动剂或拮抗剂的行为，而不是完全激动剂。

  DOI：

  10.1016/j.bmc.2009.03.023

文献信息

• Phenylnaphthalene compounds
  申请人：Poissonnier-Durieux Sophie

  公开号：US20060106111A1

  公开（公告）日：2006-05-18

  The invention relates to compounds of formula (I): wherein: A represents R 3 represents alkoxy, R 4 is as defined in the description, p is 1, 2 or 3, and medicinal products containing the same which are useful in treating or preventing melatoninergic disorders.

  该发明涉及以下化合物的结构（I）： 其中： A代表 R3代表烷氧基， R4如描述中定义， p为1、2或3， 以及含有这些化合物的药物，用于治疗或预防褪黑素失调疾病。
• [EN] BICYCLIC DERIVATIVE REGULATOR, AND PREPARATION METHOD THEREFOR AND USE THEREOF<br/>[FR] RÉGULATEUR DE DÉRIVÉ BICYCLIQUE, SON PROCÉDÉ DE PRÉPARATION ET SON UTILISATION<br/>[ZH] 双环类衍生物调节剂、其制备方法和应用
  申请人：SHANGHAI HANSOH BIOMEDICAL CO LTD

  公开号：WO2022022542A1

  公开（公告）日：2022-02-03

  一种通式(I)所示的双环类化合物或其立体异构体、其制备方法及含有该化合物的药物组合物，及其在制备治疗心血管疾病、消化系统疾病、中枢神经系统疾病和/或精神疾病药物中的用途。
• 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
• Synthesis of 3-phenylnaphthalenic derivatives as new selective MT2 melatoninergic ligands
  作者：Sophie Poissonnier-Durieux、Mohamed Ettaoussi、Basile Pérès、Jean A. Boutin、Valérie Audinot、Caroline Bennejean、Philippe Delagrange、Daniel Henri Caignard、Pierre Renard、Pascal Berthelot、Daniel Lesieur、Saïd Yous

  DOI：10.1016/j.bmc.2008.08.052

  日期：2008.9

  A series of naphthalenic analogues of melatonin were prepared and evaluated as melatonin receptor MT(2) selective ligands. Activity and MT(2) selectivity can be modulated with suitable variations of the C-3 phenyl and the acyl group on the C-1 side chain. Surprisingly, in contrast with what had been previously described in other series (2-benzylindoles, 2-benzylbenzofurans and 3-phenyltetralins), the presence of a C-3 phenyl with a functional group on the meta position seems to be primordial for MT2 afinity and selectivity. Indeed,N-[2-( 3-(3-hydroxymethylphenyl)-7-methoxynaphth-1-yl) ethyl] acetamide (21) is one of the best MT(2) selective ligands described until now and behaves as an antagonist. (C) 2008 Elsevier Ltd. All rights reserved.