4-Bromo-N-(N-benzyl-4-piperidyl)-1-methoxy-2-naphthamide | 149649-38-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: 4-Bromo-N-(N-benzyl-4-piperidyl)-1-methoxy-2-naphthamide
• 英文别名: 4-Bromo-1-methoxy-N-[1-(phenylmethyl)-4-piperidinyl]-2-naphthalenecarboxamide；N-(1-benzylpiperidin-4-yl)-4-bromo-1-methoxynaphthalene-2-carboxamide
• CAS: 149649-38-7
• 化学式: C₂₄H₂₅BrN₂O₂
• 分子量: 453.379
• InChiKey: SUQIESLQCIUEKX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  29
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  41.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  4-溴-1-甲氧基-萘-2-羧酸 在 氯化亚砜 、 三乙胺 作用下， 以 二氯甲烷 、 苯 为溶剂， 生成 4-Bromo-N-(N-benzyl-4-piperidyl)-1-methoxy-2-naphthamide
  参考文献：
  名称：

  Synthesis and Structure−Activity Relationships of Naphthamides as Dopamine D₃ Receptor Ligands

  摘要：

  A series of naphthamides were synthesized, and the affinities of these compounds were determined for dopamine D-2 and D-3 receptors using radioligand binding techniques. The naphthamide compounds that were prepared include N-(1-alkylpiperidin-4-yl)-4-bromo-1-methoxy-2-naphthamides (1-6), (S)-N-(1-alkylpyrrolidin-3-yl)-4-bromo-1-methoxy-2-naphthamides (7-12), (R)-N-(1-alkylpyrrolidin-3-yl)-4-bromo-1-methoxy-2-naphthamides (13-18), (S)-N-(1-alkyl-2-pyrrolidinylmethyl)-4-bromo-1-methoxy-2-naphthamides (19 -25), (R)-N-(1-alkyl-2-pyrrolidinylmethyl)-4-bromo-1-methoxy-2-naphthamides (26-31), and N-(9-alkyl-9-azabicyclo-[3.3.1]nonan-3 beta -yl)-4- bromo-1-methoxy-2-naphthamides (32, 33). The results of in vitro radioligand binding studies indicated that the majority of the naphthamide analogues bound with high affinity at both the D-2 and D-3 dopamine receptor subtypes and most of the compounds demonstrated some selectivity for the dopamine D-3 dopamine receptor subtype. These results demonstrated that both the structure of the central amine moiety (piperidine, pyrrolidine, and 9-azabicyclo[3.3.1]nonane) ring and the N-(alkyl) substitution on the amine significantly effects the binding affinity at D-2 and D-3 dopamine receptors. The bulkiness of the N-(1-alkyl) substituent was found to (a) have no effect on pharmacologic selectivity, (b) increase the affinity at Ds receptors, or (c) decrease the affinity at D-2 receptors. The most potent analogue in this series was (S)-N-(1-cycloheptylpyrrolidin-3-yl)-4-bromo-1-methoxy-2-naphthamide (10), which had equilibrium dissociation (K-i) values of 1.8 and 0.2 nM for D-2 and D-3 receptors, respectively. The most selective analogue was (R)-N-(1-cycloheptyl-2-pyrrolidinylmethyl)-4-bromo-1-methoxy-2-naphthamide (30), which had K-i values of 62.8 and 2.4 nM for D-2 and D-3 receptors, respectively. Radioligand binding results for sigma receptors indicated that the structure of the amine moiety and the N-(l-alkyl) substitutions also significantly influence the affinity and selectivity of these compounds at the sigma (1) and sigma (2) sigma receptor subtypes. The two naphthamides containing a 9-azabicyclo[3.3.1]nonan-3 beta -yl central ring were found to be selective for sigma (2) receptors.

  DOI：

  10.1021/jm0100077

文献信息

• Nouveaux dérivés de naphtamides, leur procédé de préparation et leur application dans le domaine thérapeutique
  申请人：INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE (INSERM)

  公开号：EP0539281A1

  公开（公告）日：1993-04-28

  Nouveaux dérivés de naphtamides, leur procédé de préparation et leur application dans le domaine thérapeutique. Les nouveaux dérivés de naphtamide conformes à l'invention sont caractérisés en ce qu'ils répondent à la formule générale (I), où X : représente soit un atome d'hydrogène, soit un atome de chlore ou de brome, soit un groupement amino- ou amino-alkyle, un groupe amino-sulfamoyle, un groupe soufré tel que thiocyanate, alkyl thio, alkyl sulfinyle ou alkyl sulfonyle, soit un groupe méthoxyle, soit un groupe nitro, soit un groupe cyano, soit un groupement électroattracteur. Y : représente un reste alkyl ou alcényl Z : représente les restes provenant de 2-aminométhyl N-alkylpyrrolidine, 2-amino-éthyl N,N diéthylamine, 2-aminoéthyl morpholine, 2 aminoéthyl , N, N, dibutylamine, 4-amino N-butyl pipéridine, 2-aminoéthylpyrrolidine.R : un hydrogène ou un substituant OCH₃. Ces nouveaux dérivés peuvent servir à la préparation de médicaments destinés à être utilisés comme agent antipsychotique, psychostimulant, antiautistique, antidépresseur, antiparkinsonien ou antihypertenseur.

  萘酰胺衍生物、其制备工艺及其治疗用途 符合本发明的新型萘酰胺衍生物的特征在于它们符合通式 (I)、 其中 X：代表氢原子，或氯原子或溴原子，或氨基或氨基烷基，或氨基氨基磺酰基，或含硫基团如硫氰酸基、烷硫基、烷基亚磺酰基或烷基磺酰基，或甲氧基，或硝基，或氰基，或夺电子基团。 Y：代表烷基或烯基残基 Z：代表来自 2-氨基甲基 N-烷基吡咯烷、2-氨基乙基 N,N-二乙胺、2-氨基乙基吗啉、2-氨基乙基 N,N,二丁胺、4-氨基 N-丁基哌啶、2-氨基乙基吡咯烷的残基。R：代表氢或 OCH₃ 取代基。这些新衍生物可用于制备抗精神病药、精神兴奋药、抗焦虑药、抗抑郁药、抗帕金森病药或抗高血压药。
• Dérivés de naphtamides, leur procédé de préparation et leur application dans le domaine thérapeutique
  申请人：INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE (INSERM)

  公开号：EP0539281B1

  公开（公告）日：1998-12-30
• US5498628A
  申请人：——

  公开号：US5498628A

  公开（公告）日：1996-03-12
• Synthesis and Structure−Activity Relationships of Naphthamides as Dopamine D₃ Receptor Ligands
  作者：Yunsheng Huang、Robert R. Luedtke、Rebekah A. Freeman、Li Wu、Robert H. Mach

  DOI：10.1021/jm0100077

  日期：2001.5.1

  A series of naphthamides were synthesized, and the affinities of these compounds were determined for dopamine D-2 and D-3 receptors using radioligand binding techniques. The naphthamide compounds that were prepared include N-(1-alkylpiperidin-4-yl)-4-bromo-1-methoxy-2-naphthamides (1-6), (S)-N-(1-alkylpyrrolidin-3-yl)-4-bromo-1-methoxy-2-naphthamides (7-12), (R)-N-(1-alkylpyrrolidin-3-yl)-4-bromo-1-methoxy-2-naphthamides (13-18), (S)-N-(1-alkyl-2-pyrrolidinylmethyl)-4-bromo-1-methoxy-2-naphthamides (19 -25), (R)-N-(1-alkyl-2-pyrrolidinylmethyl)-4-bromo-1-methoxy-2-naphthamides (26-31), and N-(9-alkyl-9-azabicyclo-[3.3.1]nonan-3 beta -yl)-4- bromo-1-methoxy-2-naphthamides (32, 33). The results of in vitro radioligand binding studies indicated that the majority of the naphthamide analogues bound with high affinity at both the D-2 and D-3 dopamine receptor subtypes and most of the compounds demonstrated some selectivity for the dopamine D-3 dopamine receptor subtype. These results demonstrated that both the structure of the central amine moiety (piperidine, pyrrolidine, and 9-azabicyclo[3.3.1]nonane) ring and the N-(alkyl) substitution on the amine significantly effects the binding affinity at D-2 and D-3 dopamine receptors. The bulkiness of the N-(1-alkyl) substituent was found to (a) have no effect on pharmacologic selectivity, (b) increase the affinity at Ds receptors, or (c) decrease the affinity at D-2 receptors. The most potent analogue in this series was (S)-N-(1-cycloheptylpyrrolidin-3-yl)-4-bromo-1-methoxy-2-naphthamide (10), which had equilibrium dissociation (K-i) values of 1.8 and 0.2 nM for D-2 and D-3 receptors, respectively. The most selective analogue was (R)-N-(1-cycloheptyl-2-pyrrolidinylmethyl)-4-bromo-1-methoxy-2-naphthamide (30), which had K-i values of 62.8 and 2.4 nM for D-2 and D-3 receptors, respectively. Radioligand binding results for sigma receptors indicated that the structure of the amine moiety and the N-(l-alkyl) substitutions also significantly influence the affinity and selectivity of these compounds at the sigma (1) and sigma (2) sigma receptor subtypes. The two naphthamides containing a 9-azabicyclo[3.3.1]nonan-3 beta -yl central ring were found to be selective for sigma (2) receptors.