2-(4-bromobutyl)hexahydro-4,7-etheno-1H-cyclobutisoindole-1,3(2H)-dione | 114222-39-8

• 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-bromobutyl)hexahydro-4,7-etheno-1H-cyclobutisoindole-1,3(2H)-dione
• 英文别名: 4-bromo-1-(3a,4,4a,6a,7,7a-hexahydro-4,7-etheno-1H-cyclobut[f]isoindol-1,3-dionyl)-butane；2-(4-bromobutyl)-1,3-dioxo-4,7-etheno-1,3,3a,4,4a,6a,7,7a-octahydro-2H-cyclobut[f]isoindole；4-(4-Bromobutyl)-4-azatetracyclo[5.4.2.02,6.08,11]trideca-9,12-diene-3,5-dione
• CAS: 114222-39-8
• 化学式: C₁₆H₁₈BrNO₂
• 分子量: 336.228
• InChiKey: MYMXLCKEHGEQPD-UHFFFAOYSA-N

物化性质

• 沸点：
  491.8±45.0 °C(Predicted)
• 密度：
  1.474±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  37.4
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-(4-bromobutyl)hexahydro-4,7-etheno-1H-cyclobutisoindole-1,3(2H)-dione 、 MK 212盐酸盐 在 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 4-[4-[4-(6-Chloropyrazin-2-yl)piperazin-1-yl]butyl]-4-azatetracyclo[5.4.2.02,6.08,11]trideca-9,12-diene-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：

  1,3,5,7-cyclooctatetraene 在 sodium hydride 作用下， 以 甲苯 为溶剂， 反应 0.5h， 生成 2-(4-bromobutyl)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

• Indole derivatives and their use
  申请人：Novo Nordisk A/S

  公开号：US05126363A1

  公开（公告）日：1992-06-30

  Indole derivatives of formula (I) ##STR1## wherein R.sup.1, R.sup.2, R.sup.3 and R.sup.4 may be hydrogen or lower alkyl optionally substituted by halogen; A.sup.1 represents a straight or branched alkylene chain containing from 2 to 4 carbon atoms; R.sup.5 is hydrogen or a straight or branched alkyl group; A.sup.2 is a straight or branched, saturated or unsaturated hydrocarbon chain containing from 2 to 6 carbon atoms; and R.sup.6 is selected from a group consisting of various structures, have been found to exhibit central nervous system activities.

  式(I)的吲哚衍生物##STR1##其中R.sup.1、R.sup.2、R.sup.3和R.sup.4可以是氢或由卤素取代的较低烷基；A.sup.1代表含有2至4个碳原子的直链或支链烷基链；R.sup.5是氢或直链或支链烷基基团；A.sup.2是含有2至6个碳原子的直链或支链、饱和或不饱和的碳氢链；R.sup.6从各种结构中选择，已发现具有中枢神经系统活性。
• 5-HT selective agents
  申请人：Abbott Laboratories

  公开号：US05049564A1

  公开（公告）日：1991-09-17

  Substituted 8-alkoxy-1,2,3,3a,8,8a-hexahydroindeno-[1,2-c]pyrroles; 5-alkoxy-2,3,4,4a,9,9a-hexahydro-1H-indeno[2,1-c]pyridines; and 9-alkoxy-2,3,3a,4,5,9a-hexahydro-1H-benz[e]isoindoles are selective 5-HT receptor agents and are thus useful in the treatment of anxiety, depression, and hypertension.

  8-烷氧基-1,2,3,3a,8,8a-六氢吲哚[1,2-c]吡咯；5-烷氧基-2,3,4,4a,9,9a-六氢-1H-吲哚[2,1-c]吡啶；以及9-烷氧基-2,3,3a,4,5,9a-六氢-1H-苯[e]异喹啉是选择性5-HT受体药物，因此可用于治疗焦虑症、抑郁症和高血压。
• Aza spiro decane and use thereof in treating CNS disorders
  申请人：Novo Nordisk A/S

  公开号：US05227488A1

  公开（公告）日：1993-07-13

  Indole derivatives of formula (I) ##STR1## wherein R.sup.1, R.sup.2, R.sup.3 and R.sup.4 may be hydrogen or lower alkyl optionally substituted by halogen; X represents oxygen or sulfur; A.sup.1 represents a straight or branched alkylene chain containing from 2 to 4 carbon atoms; R.sup.5 is hydrogen or a straight or branched alkyl group; A.sup.2 is a straight or branched, saturated or unsaturated hydrocarbon chain containing from 2 to 6 carbon atoms; and R.sup.6 is selected from a group consisting of various structures, have been found to exhibit central nervous system activities.

  式(I)的吲哚衍生物：##STR1## 其中，R.sup.1，R.sup.2，R.sup.3和R.sup.4可以是氢或低碳烷基，可选地被卤素取代；X代表氧或硫；A.sup.1代表含有2至4个碳原子的直链或支链烷基链；R.sup.5是氢或直链或支链烷基；A.sup.2是含有2至6个碳原子的直链或支链、饱和或不饱和的碳氢链；R.sup.6从各种结构中选择，已发现具有中枢神经系统活性。
• Meyer; DeBernardis; Hancock, Journal of Medicinal Chemistry, 1994, vol. 37, # 1, p. 105 - 112
  作者：Meyer、DeBernardis、Hancock

  DOI：——

  日期：——
• INDOLE DERIVATIVES, THEIR PREPARATION AND USE
  申请人：NOVO NORDISK A/S

  公开号：EP0495826A1

  公开（公告）日：1992-07-29