N-{2-[(5-Hydroxy-1,2,3,4-tetrahydro-naphthalen-2-yl)-propyl-amino]-ethyl}-benzamide | 257294-04-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 四氢化萘
• 英文名称: N-{2-[(5-Hydroxy-1,2,3,4-tetrahydro-naphthalen-2-yl)-propyl-amino]-ethyl}-benzamide
• CAS: 257294-04-5
• 化学式: C₂₂H₂₈N₂O₂
• 分子量: 352.477
• InChiKey: YIIVQYPQZUMKIO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.39
• 重原子数：
  26.0
• 可旋转键数：
  7.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  52.57
• 氢给体数：
  2.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  N-{2-[(5-Hydroxy-1,2,3,4-tetrahydro-naphthalen-2-yl)-propyl-amino]-ethyl}-benzamide 在 bis-triphenylphosphine-palladium(II) chloride 2,4-di-tert.-butyl-4-methylphenol 、 三乙胺 、 三苯基膦 、 lithium chloride 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 0.75h， 生成
  参考文献：
  名称：

  C5-Substituted Derivatives of 5-OMe-BPAT: Synthesis and Interactions with Dopamine D2 and Serotonin 5-HT1A Receptors

  摘要：

  Eight new C5-substituted derivatives of the potential atypical antipsychotic agent 5-methoxy-2-[N-(2-benzamidoethyl)-N-n-propylamino]tetralin (5-OMe-BPAT, 1) have been prepared by chemical conversion of the 5-trifluoromethylsulfonyloxy (triflate) analogue 4 via various Stille-type cross-couplings, a Heck reaction, and an amidation in moderate to good yields. The 5-acetyl, 5-cyano, 5-methyl, 5-(2-furyl), 5-phenyl, methyl 5-carboxylate, and the 5-carboxamido analogues 5-11 thus obtained, the previously disclosed 5-methoxy, 5-hydroxy, and 5-unsubstituted analogues 1-3, and the 5-triflate analogue 4 were evaluated for their ability to compete for [H-3]-spiperone binding to rat striatal membranes containing dopamine D-2 receptors, and their ability to compete for [H-3]-8-OH-DPAT. binding to rat frontal cortex membranes containing serotonin 5-HT1A receptors in vitro. Compounds 1-11 displayed weak to high affinities for dopamine D-2 receptors, with K-i-values ranging from 550 nM for the 5-carboxamido analogue to 4.9 nM for the 5-hydroxy analogue. The relative affinities of the 5-methoxy, 5-hydroxy, and 5-unsubstituted analogues suggested that these compounds may bind to the same site and in a similar way as the 5-oxygenated DPATs, with the 5-methoxy substituent of 1 functioning as a hydrogen bond acceptor. The serotonin 5-HT1A receptor tolerated more structural diversity at the C5-position of 1 as revealed by the higher K-i-values of 1-11. which ranged from 60 nM for the 5-carboxamido analogue to 1.0 nM for the 5-unsubstituted analogue. Partial least-squares (PLS) analysis of a set of 24 molecular descriptors, generated for each analogue, revealed no significant correlation between the dopamine D-2 receptor affinities of 1-11 and their molecular properties, supporting the view that they may have different binding modes at this receptor subtype. A PLS model with moderate predictability (Q(2) = 0.49) could be derived for the serotonin 5-HT1A receptor affinities of 1-11. According to the model, a relatively lipophilic, nonpolar CS-substituent should be optimal for a high affinity at this receptor subtype. (C) 1999 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(99)00196-0
• 作为产物：
  描述：

  5-甲氧基-n-丙基-2-氨基四氢化萘盐酸盐 在 sodium hydroxide 、 lithium aluminium tetrahydride 、 三溴化硼 、 potassium carbonate 、 potassium iodide 作用下， 以 四氢呋喃 、 二氯甲烷 、 丙酮 为溶剂， 反应 19.0h， 生成 N-{2-[(5-Hydroxy-1,2,3,4-tetrahydro-naphthalen-2-yl)-propyl-amino]-ethyl}-benzamide
  参考文献：
  名称：

  具有混合多巴胺D2，D3和5-羟色胺5-HT1A受体结合特性的2-氨基四氢萘衍生的取代苯甲酰胺：一类新的潜在的非典型抗精神病药。

  摘要：

  通过结合2-（N，N-di-n-propylpropylamino）的结构特征，设计了一种新的化学类潜在的非典型抗精神病药，其基于混合的多巴胺D2受体拮抗作用和血清素5-HT1A受体激动作用的药理学概念结构杂化物中的四氢萘酮（DPAT）和2-吡咯烷基甲基衍生的取代苯甲酰胺。因此，合成了35种不同的2-氨基四氢萘衍生的取代的苯甲酰胺系列，并评估了这些化合物竞争与[3H]-雷氯必利与克隆的人多巴胺D2A和D3受体结合以及[3H] -8的竞争能力。 -OH-DPAT在体外与大鼠血清素5-HT1A受体结合。该系列的先导化合物5-甲氧基-2- [N-（2-苯甲酰胺基乙基）-Nn-丙基氨基]四氢化萘（12a）对多巴胺D2A受体表现出高亲和力（Ki = 3.2 nM），多巴胺D3受体（Ki = 0.58 nM）以及血清素5-HT1A受体（Ki = 0.82 nM）。该系列的结构亲和关系表明，在所有三种受

  DOI：

  10.1016/s0968-0896(98)00167-9