4-[2-(acetylamino)ethyl]-6-methoxy-2-naphthoic acid | 225786-11-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 4-[2-(acetylamino)ethyl]-6-methoxy-2-naphthoic acid
• 英文别名: 4-(2-Acetamidoethyl)-6-methoxynaphthalene-2-carboxylic acid
• CAS: 225786-11-8
• 化学式: C₁₆H₁₇NO₄
• 分子量: 287.315
• InChiKey: GZBUVJWKZATTNG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  21
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  75.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-[2-(acetylamino)ethyl]-6-methoxy-2-naphthoic acid 在 lithium aluminium tetrahydride 、 氯化亚砜 、 二乙胺基三氟化硫 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 3.0h， 生成 N-[2-(3-fluoromethyl-7-methoxy-naphthalen-1-yl)ethyl]acetamide
  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 aluminum (III) chloride 、 sodium hypochlorite 、 水 、 potassium iodide 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 1.0h， 生成 4-[2-(acetylamino)ethyl]-6-methoxy-2-naphthoic acid
  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

文献信息

• Nouveaux composés naphtaléniques, leur procédé de préparation et les compositions pharmaceutiques quiles contiennent
  申请人：ADIR ET COMPAGNIE

  公开号：EP0919541A1

  公开（公告）日：1999-06-02

  Composé de formule (I) : dans laquelle : T représente une chaîne alkylène, A et B forment ensemble un groupement naphtalène, dihydronaphtalène, ou tétrahydronapthalène, R représente un hydrogène, un groupement hydroxy, R' ou OR', R' étant tel que défini dans la description, G1 représente un halogène, un radical R1 ou un groupement -O-CO-R1, R1 étant tel que défini dans la description, G2 représente un groupement choisi parmi : X, R2 et R21 étant tels que définis dans la description. Medicaments

  式 (I) 的化合物 其中： T 代表亚烷基链、 A 和 B 共同形成萘、二氢萘或四氢萘基团、 R 代表氢、羟基、R'或 OR'基团，R'如说明中所定义、 G1 代表卤素、基团 R1 或基团-O-CO-R1，其中 R1 如说明中所定义、 G2 代表选自......的基团 X、R2 和 R21 如说明中所定义。 药物
• US6143789A
  申请人：——

  公开号：US6143789A

  公开（公告）日：2000-11-07
• [EN] NOVEL NAPHTHALENE DERIVATIVES, PROCESS FOR THE PREPARATION THEREOF AND PHARMACEUTICAL COMPOSITIONS CONTAINING SAME<br/>[FR] NOUVEAUX DERIVES NAPHTALENIQUES, LEUR PROCEDE DE PREPARATION ET LES COMPOSITIONS PHARMACEUTIQUES QUI LES CONTIENNENT
  申请人：SERVIER LAB

  公开号：WO2009022065A2

  公开（公告）日：2009-02-19

  Composés de formule (I) : dans laquelle : R1 représente un alkyle, alkényle, halogénoalkyle, polyhalogénoalkyle, cycloalkyle, cycloalkylalkyle, aryle, arylalkyle, hétéroaryle ou hétéroarylalkyle R2 et R3 représentent un atome d'hydrogène ou un groupement alkyle Médicaments.
• Design, synthesis and pharmacological evaluation of new series of naphthalenic analogues as melatoninergic (MT1/MT2) and serotoninergic 5-HT2C dual ligands (I)
  作者：Mohamed Ettaoussi、Ahmed Sabaouni、Marouan Rami、Jean A. Boutin、Philippe Delagrange、Pierre Renard、Michael Spedding、Daniel-Henri Caignard、Pascal Berthelot、Saïd Yous

  DOI：10.1016/j.ejmech.2012.01.027

  日期：2012.3

  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.