2-<4-<4-(2-pyrimidinyl)-1-piperazinyl>butyl>hexahydro-4,7-etheno-1H-cyclobutisoindole-1,3(2H)-dione | 114298-18-9

• 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: 2-<4-<4-(2-pyrimidinyl)-1-piperazinyl>butyl>hexahydro-4,7-etheno-1H-cyclobutisoindole-1,3(2H)-dione
• 英文别名: 2-{4-[4-(2-pyrimidinyl)-1-piperazinyl]butyl}hexahydro-4,7-etheno-1H-cyclobut[f]isoindole-1,3(2H)-dione；(1R,2S,6R,7S,8S,11R)-4-[4-(4-pyrimidin-2-ylpiperazin-1-yl)butyl]-4-azatetracyclo[5.4.2.02,6.08,11]trideca-9,12-diene-3,5-dione
• CAS: 114298-18-9
• 化学式: C₂₄H₂₉N₅O₂
• 分子量: 419.527
• InChiKey: AERLHOTUXIJQFV-AIAJZDAFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  31
• 可旋转键数：
  6
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  69.6
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  3a,4,4a,6a,7,7a-hexahydro-4,7-etheno-1H-cyclobutisoindole-1,3(2H)-dione 在 sodium hydride 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 24.5h， 生成 2-<4-<4-(2-pyrimidinyl)-1-piperazinyl>butyl>hexahydro-4,7-etheno-1H-cyclobutisoindole-1,3(2H)-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

文献信息

• COMPOUNDS FOR PROTECTION OF PHOTORECEPTOR CELLS AND FOR ENHANCING VISUAL FUNCTION UNDER LOW LIGHT CONDITIONS
  申请人：Allergan, Inc.

  公开号：US20150328221A1

  公开（公告）日：2015-11-19

  Described herein are methods of enhancing visual function under low light conditions and to methods of protecting photoreceptors cells by administration of a compound selected from the group consisting of zalospirone and eptapirone; or a pharmaceutically acceptable salt thereof.