hexahydro-4,6-ethanocycloprop[f]isoindole-1,3-(2H,3aH)-dione | 63108-25-8

• 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: hexahydro-4,6-ethanocycloprop[f]isoindole-1,3-(2H,3aH)-dione
• 英文别名: 4-azatetracyclo[5.3.2.02,6.08,10]dodecane-3,5-dione
• CAS: 63108-25-8
• 化学式: C₁₁H₁₃NO₂
• 分子量: 191.23
• InChiKey: HDEIXOPVEIKRBE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  14
• 可旋转键数：
  0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.82
• 拓扑面积：
  46.2
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  hexahydro-4,6-ethanocycloprop[f]isoindole-1,3-(2H,3aH)-dione 在 sodium hydride 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 生成 2-[4-[4-(3-chloro-2-pyrazinyl)-1-piperazinyl]butyl]hexahydro-4,6-ethanocycloprop[f]isoindole-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

• Fused bicyclic imides with psychotropic activity
  申请人：American Home Products Corporation

  公开号：US04892943A1

  公开（公告）日：1990-01-09

  There are disclosed compounds of the formula ##STR1## wherein R.sup.1 and R.sup.2 represent the structure ##STR2## R.sup.3 and R.sup.4 are hydrogen, or R.sup.3 and R.sup.4 taken together form a 3-5 membered saturated carbocyclic ring; R.sup.5 and R.sup.6 are hydrogen, or R.sup.5 and R.sup.6 taken together form a 3-6 membered carbocyclic ring or a cyclobutenyl ring; with the proviso that when R.sup.3, R.sup.4, R.sup.5 and R.sup.6 are hydrogen, n is other than zero; m is 2-4; n is 0-4; X is lower alkylene, vinylene or O; R.sup.7 is unsubstituted or substituted phenyl, 2-pyridinyl, 2-pyrimidinyl, 2-pyrazinyl or 3-pyridazinyl; where the substituents are selected from the group lower alkyl, lower alkoxy, halo, cyano, nitro and trifluoromethyl; and the pharmaceutically acceptable salts thereof and their use as antipsychotic/anxiolytic agents having a low liability for extrapyramidal side effects.

  公开了式子为##STR1##的化合物，其中R.sup.1和R.sup.2代表结构##STR2##，R.sup.3和R.sup.4为氢，或R.sup.3和R.sup.4共同形成一个3-5成员的饱和碳环；R.sup.5和R.sup.6为氢，或R.sup.5和R.sup.6共同形成一个3-6成员的碳环或环丁烯基环；但是当R.sup.3，R.sup.4，R.sup.5和R.sup.6为氢时，n不为零；m为2-4；n为0-4；X为低位烷基，乙烯基或O；R.sup.7为未取代或取代的苯基，2-吡啶基，2-嘧啶基，2-吡嗪基或3-吡啶唑基；其中取代基选自群体低位烷基，低位烷氧基，卤素，氰基，硝基和三氟甲基；以及它们的药学上可接受的盐和它们作为抗精神病/抗焦虑药物使用，具有低的锥体外系副作用。
• ABOU-GHARBIA, MAGID;PATEL, USHA R.;WEBB, MICHAEL B.;MOYER, JOHN A.;ANDREE+, J. MED. CHEM., 31,(1988) N 7, 1382-1392
  作者：ABOU-GHARBIA, MAGID、PATEL, USHA R.、WEBB, MICHAEL B.、MOYER, JOHN A.、ANDREE+

  DOI：——

  日期：——
• US4892943A
  申请人：——

  公开号：US4892943A

  公开（公告）日：1990-01-09
• US7655688B2
  申请人：——

  公开号：US7655688B2

  公开（公告）日：2010-02-02
• 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.