3a,4,4a,5,6,6a,7,7a-octahydro-4,9-etheno-1H-cyclooctapyrrole-1,3(2H)-dione | 23852-39-3

• 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: 3a,4,4a,5,6,6a,7,7a-octahydro-4,9-etheno-1H-cyclooctapyrrole-1,3(2H)-dione
• 英文别名: octahydro-4,7-etheno-1H-cyclobut[f]isoindole-1,3(2H)-dione；4-Azatetracyclo[5.4.2.02,6.08,11]tridec-12-ene-3,5-dione
• CAS: 23852-39-3
• 化学式: C₁₂H₁₃NO₂
• 分子量: 203.241
• InChiKey: JMASAISQNFPKMG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  15
• 可旋转键数：
  0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.67
• 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：

  3a,4,4a,5,6,6a,7,7a-octahydro-4,9-etheno-1H-cyclooctapyrrole-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， 生成 4-[4-[4-(6-Chloropyridazin-3-yl)piperazin-1-yl]butyl]-4-azatetracyclo[5.4.2.02,6.08,11]tridec-12-ene-3,5-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
• 作为产物：
  描述：

  马来酰亚胺 、 环辛二烯 以 xylene 为溶剂， 以54%的产率得到3a,4,4a,5,6,6a,7,7a-octahydro-4,9-etheno-1H-cyclooctapyrrole-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

• 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.

  公开了以下式子的化合物：##STR1## 其中R.sup.1和R.sup.2代表结构##STR2## R.sup.3和R.sup.4是氢，或R.sup.3和R.sup.4共同形成3-5成员的饱和碳环；R.sup.5和R.sup.6是氢，或R.sup.5和R.sup.6共同形成3-6成员的碳环或环丁烯基环；但当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为低碳基，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；其中取代基被选择自下列群组：低烷基，低烷氧基，卤素，氰基，硝基和三氟甲基；以及其药学上可接受的盐和它们作为具有低外周神经作用副作用的抗精神病/抗焦虑剂的用途。
• 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
• US4957913A
  申请人：——

  公开号：US4957913A

  公开（公告）日：1990-09-18
• 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.