2-<4-<1-(chloro-2-pyrazinyl)-4-piperidinyl>butyl>-4,4a,5,5a,6,6a-hexahydro-4,6-ethenocyclopropisoindole-1,3(2H,3aH)-dione | 114222-71-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异吲哚及其衍生物
• 英文名称: 2-<4-<1-(chloro-2-pyrazinyl)-4-piperidinyl>butyl>-4,4a,5,5a,6,6a-hexahydro-4,6-ethenocyclopropisoindole-1,3(2H,3aH)-dione
• 英文别名: 2-[4-[1-(6-chloro-2-pyrazinyl)-4-piperidinyl]butyl]-4,4a,5,5a,6,6a-hexahydro-4,6-ethenocycloprop[f]isoindole-1,3-(2H,3aH)-dione；4-[4-[1-(6-Chloropyrazin-2-yl)piperidin-4-yl]butyl]-4-azatetracyclo[5.3.2.02,6.08,10]dodec-11-ene-3,5-dione
• CAS: 114222-71-8
• 化学式: C₂₄H₂₉ClN₄O₂
• 分子量: 440.973
• InChiKey: WSWGAWAOUISRKA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  31
• 可旋转键数：
  6
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  66.4
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  1,3-dioxo-2H-4,6-etheno-1,3,3a,6a-tetrahydrocyclopropisoindole 在 Rh/Al₂O₃ 氢气 、 caesium carbonate 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 25.0 ℃ 、344.73 kPa 条件下， 反应 99.0h， 生成 2-<4-<1-(chloro-2-pyrazinyl)-4-piperidinyl>butyl>-4,4a,5,5a,6,6a-hexahydro-4,6-ethenocyclopropisoindole-1,3(2H,3aH)-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

• ABOU-GHARBIA, MAGID A.
  作者：ABOU-GHARBIA, MAGID A.

  DOI：——

  日期：——
• US4851533A
  申请人：——

  公开号：US4851533A

  公开（公告）日：1989-07-25
• US4883875A
  申请人：——

  公开号：US4883875A

  公开（公告）日：1989-11-28
• US4900835A
  申请人：——

  公开号：US4900835A

  公开（公告）日：1990-02-13
• Polycyclic aryl- and heteroarylpiperazinyl imides as 5-HT1A receptor ligands and potential anxiolytic agents: synthesis and structure-activity relationship studies
  作者：Magid Abou-Gharbia、Usha R. Patel、Michael B. Webb、John A. Moyer、Terrance H. Andree、Eric A. Muth

  DOI：10.1021/jm00402a023

  日期：1988.7

  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.