(1R,4S,4aR,5S,8R,8aS)-10-(4-(4-(pyrimidin-2-yl)piperazin-1-yl)butyl)octahydro-1,4:5,8-dimethano-4a,8a-(methanoiminomethano)naphthalene-9,11-dione | 114222-64-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: (1R,4S,4aR,5S,8R,8aS)-10-(4-(4-(pyrimidin-2-yl)piperazin-1-yl)butyl)octahydro-1,4:5,8-dimethano-4a,8a-(methanoiminomethano)naphthalene-9,11-dione
• CAS: 114222-64-9
• 化学式: C₂₆H₃₅N₅O₂
• 分子量: 449.596
• InChiKey: OSVVGECYSBZWFD-RFDKZGJCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.58
• 重原子数：
  33.0
• 可旋转键数：
  6.0
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.77
• 拓扑面积：
  69.64
• 氢给体数：
  0.0
• 氢受体数：
  6.0

反应信息

• 作为产物：
  描述：

  (1R,4S,4aS,8aR)-octahydro-1,4:5,8-dimethano-4a,8a-(methanooxymethano)naphthalene-9,11-dione 、 4-氨基丁基-1-(2-嘧啶)-哌嗪 在 吡啶 作用下， 以50%的产率得到(1R,4S,4aR,5S,8R,8aS)-10-(4-(4-(pyrimidin-2-yl)piperazin-1-yl)butyl)octahydro-1,4:5,8-dimethano-4a,8a-(methanoiminomethano)naphthalene-9,11-dione
  参考文献：
  名称：

  Polycyclic aryl- and heteroarylpiperazinyl imides as 5-HT1A receptor ligands and potential anxiolytic agents: synthesis and structure-activity relationship studies

  摘要：

  A series of polycyclic aryl- and heteroarylpiperazinyl imides were prepared and tested in various receptor-binding and behavioral tests. Parameters measured included in vitro inhibition of D2 and 5-HT1A receptor binding, inhibition of apomorphine (APO) induced stereotyped and climbing behavior, and activity in blocking conditioned avoidance responding (CAR). Several compounds demonstrated moderate to high affinity for the 5-HT1A receptor binding site; compounds 27 and 36 containing the serotonin mimetic (o-methoxyphenyl)piperazinyl moiety and compounds 42 and 50 containing the 2-pyrimidinylpiperazinyl moiety displayed the highest affinity, being equal to that of the 5-HT1A agonist 8-OH-DPAT (Ki = 1-1.3 nM). In addition to affinity at 5-HT1A binding sites, many compounds were active in blocking CAR. Compound 34, 2-[4-[4-(2-pyrimidinyl)-1-piperazinyl]butyl]hexahydro-4,7-etheno-1H- cyclobut[f]isoindole-1,3(2H)-dione, demonstrated 3 times the activity of buspirone, blocking CAR in rats with an AB50 of 13 mg/kg. It also displayed high affinity for the 5-HT1A receptor (Ki = 16 nM), which is at least 20 times higher than its affinity for D2 (Ki = 345 nM) and 5-HT2 (Ki = 458 nM) receptors. Compound 34 was selected for further preclinical and pharmacokinetic evaluations for possible development as an anxiolytic agent. Structure-activity relationships within this series are discussed.

  DOI：

  10.1021/jm00402a023