2-(4-(4-(萘-1-基)哌嗪-1-基)丁基)异二氢吲哚-1,3-二酮 | 115338-25-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 中文名称: 2-(4-(4-(萘-1-基)哌嗪-1-基)丁基)异二氢吲哚-1,3-二酮
• 英文名称: 2-(4-(4-(naphthalen-1-yl)piperazin-1-yl)butyl)isoindoline-1,3-dione
• 英文别名: 2-[4-(naphthalin-1-yl-piperazin-1-yl)-butyl]-isoindolin-1,3-dione；2-[4-(4-Naphthalen-1-yl-piperazin-1-yl)-butyl]-isoindole-1,3-dione；2-[4-(4-naphthalen-1-ylpiperazin-1-yl)butyl]isoindole-1,3-dione
• CAS: 115338-25-5
• 化学式: C₂₆H₂₇N₃O₂
• 分子量: 413.519
• InChiKey: PPTMLGGLVHEJJN-UHFFFAOYSA-N

物化性质

• 熔点：
  256-260 °C(Solv: methanol (67-56-1))
• 沸点：
  604.5±50.0 °C(Predicted)
• 密度：
  1.230±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  31
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  43.9
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-(4-(4-(萘-1-基)哌嗪-1-基)丁基)异二氢吲哚-1,3-二酮 在 肼 作用下， 以 乙醇 为溶剂， 反应 2.0h， 生成 4-(4-(naphthalen-1-yl)piperazin-1-yl)butan-1-amine
  参考文献：
  名称：

  5-HT1A 5-羟色胺拮抗剂1-（2-甲氧基苯基）-4- [4-（2-邻苯二甲酰亚胺基）丁基]哌嗪的类似物，其α1-肾上腺素亲和力降低。

  摘要：

  1-（2-甲氧基苯基）-4- [4-（2-邻苯二甲酰亚胺基）丁基]哌嗪（NAN-190; 1a）是一种可能的突触后5-HT1A 5-羟色胺拮抗剂。这种高亲和力配体（Ki = 0.6 nM）尽管对5-HT1A具有选择性，但对其他5-HT受体具有选择性，但在α1-肾上腺素受体（Ki = 0.8 nm）处具有几乎相同的亲和力。进行结构亲和关系研究以实现改进的选择性。用取代的苯甲酰胺替代邻苯二甲酰亚胺部分导致保留5-HT1A亲和力，但选择性没有改善，而烷基酰胺替代证明是有益的，从而导致亲和力和选择性提高。将α分支到酰胺羰基上并增加烷基部分的体积，进一步提高了5-HT1A的亲和力和选择性。发现4- [4-（1-金刚烷甲酰胺基）丁基] -1-（2-甲氧基苯基）哌嗪（2j）在5-HT1A位点具有高亲和力（Ki = 0.4 nM）结合，选择性是后者的160倍。 α1肾上腺素位点。初步研究表明，该药物保留了

  DOI：

  10.1021/jm00112a043
• 作为产物：
  描述：

  1-萘胺 在 potassium carbonate 作用下， 以 二乙二醇二甲醚 、 丙酮 为溶剂， 反应 48.0h， 生成 2-(4-(4-(萘-1-基)哌嗪-1-基)丁基)异二氢吲哚-1,3-二酮
  参考文献：
  名称：

  High Affinity Dopamine D₃ Receptor (D₃R)-Selective Antagonists Attenuate Heroin Self-Administration in Wild-Type but not D₃R Knockout Mice

  摘要：

  The dopamine D-3 receptor (D3R) is a promising target for the development of pharmacotherapeutics to treat substance use disorders. Several D3R-selective antagonists are effective in animal models of drug abuse, especially in models of relapse. Nevertheless, poor bioavailability, metabolic instability, and/or predicted toxicity have impeded success in translating these drug candidates to clinical use. Herein, we report a series of D3R-selective 4-phenylpiperazines with improved metabolic stability. A subset of these compounds was evaluated for D3R functional efficacy and off-target binding at selected 5-HT receptor subtypes, where significant overlap in SAR with D3R has been observed. Several high affinity D3R antagonists, including compounds 16 (K-i = 0.12 nM) and 32 (K-i = 0.35 nM), showed improved metabolic stability compared to the parent compound, PG648 (6). Notably, 16 and the classic D3R antagonist SB277011A (2) were effective in reducing selfadministration of heroin in wild-type but not D3R knockout mice.

  DOI：

  10.1021/acs.jmedchem.5b00776

文献信息

• Arylpiperazine derivatives as high-affinity 5-HT1A serotonin ligands
  作者：Richard A. Glennon、Noreen A. Naiman、Robert A. Lyon、Milt Titeler

  DOI：10.1021/jm00118a018

  日期：1988.10

  Although simple arylpiperazines are commonly considered to be moderately selective for 5-HT1B serotonin binding sites, N4-substitution of such compounds can enhance their affinity for 5-HT1A sites and/or decrease their affinity for 5-HT1B sites. A small series of 4-substituted 1-arylpiperazines was prepared in an attempt to develop agents with high affinity for 5-HT1A sites. Derivatives where the aryl portion is phenyl, 2-methoxyphenyl, or 1-naphthyl, and the 4-substituent is either a phthalimido or benzamido group at a distance of four methylene units away from the piperazine 4-position, display high affinity for these sites. One of these compounds, 1-(2-methoxyphenyl)-4-[4-(2-phthalimido)butyl]piperazine (18), possesses a higher affinity than 5-HT and represents the highest affinity (Ki = 0.6 nM) agent yet reported for 5-HT1A sites.