4-[4-(2-pyrazinyl)-1-piperazinyl]butylamine | 114222-98-9

• 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: 4-[4-(2-pyrazinyl)-1-piperazinyl]butylamine
• 英文别名: 1-(4-aminobutyl)-4-(2-pyrazinyl)piperazine；1-Piperazinebutanamine, 4-(2-pyrazinyl)-；4-(4-pyrazin-2-ylpiperazin-1-yl)butan-1-amine
• CAS: 114222-98-9
• 化学式: C₁₂H₂₁N₅
• mdl: MFCD11620572
• 分子量: 235.332
• InChiKey: HKMSGDHYCSNJPB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.2
• 重原子数：
  17
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.666
• 拓扑面积：
  58.3
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  三环[3.2.2.02,4]壬-8-烯-6,7-二甲酸酐 、 4-[4-(2-pyrazinyl)-1-piperazinyl]butylamine 在 吡啶 作用下， 生成 4,4a,5,5a,6,6a-hexahydro-2-[4-[4-(2-pyrazinyl)-1-piperazinyl]butyl]-4,6-ethenocycloprop[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 heterotricyclic imides with psychotropic activity and
  申请人：American Home Products Corporation

  公开号：US05053508A1

  公开（公告）日：1991-10-01

  There are disclosed compounds of the formula ##STR1## wherein R.sup.1 and R.sup.2 taken together represent ##STR2## R.sup.3 and R.sup.4 are hydrogen; R.sup.5 is 2-pyridinyl, 2-pyrazinyl, 2-pyrimidinyl, 3-pyridazinyl or any of the foregoing R.sup.5 moieties substituted by lower alkyl, lower alkoxy, halo lower alkyl, cyano, nitro or halo; X, Y and Z are, independently, N, S, O, NR.sup.6, SO, SO.sub.2, CR.sup.6 or CH.sub.2 ; A is lower alkylene, O or S; R.sup.6 is hydrogen, lower alkyl, aryl, aralkyl; m is 3-7; and the pharmaceutically acceptable salts thereof, and their use as antipsychotic/-anxiolytic agents having a low liability for extrapyramidal side effects.

  已披露的化合物的结构式如下：其中R.sup.1和R.sup.2一起代表；R.sup.3和R.sup.4为氢；R.sup.5为2-吡啶基、2-吡嗪基、2-嘧啶基、3-吡啉啉或上述任一R.sup.5基团的较低烷基、较低烷氧基、卤代较低烷基、氰基、硝基或卤素取代；X、Y和Z独立地为N、S、O、NR.sup.6、SO、SO.sub.2、CR.sup.6或CH.sub.2；A为较低烷基、O或S；R.sup.6为氢、较低烷基、芳基、芳基烷基；m为3-7；及其药用盐，用作具有低外侧锥体副作用风险的抗精神病/抗焦虑药物。
• Psychotropic bicyclic imides
  申请人：American Home Products Corporation

  公开号：US04748240A1

  公开（公告）日：1988-05-31

  Substituted imides of the following formula are antipsychotic, anxiolytic agents with very little extrapyramidal side effects: ##STR1## in which X is --O--, --S--, --SO--, --SO.sub.2 --, --CR.sub.3 R.sub.4 --where R.sub.3 and R.sub.4, independently, are hydrogen, alkyl of 1 to 4 carbon atoms or, taken together with the carbon atom to which they are attached, R.sub.3 and R.sub.4 form a cycloalkyl group of 3 to 5 carbon atoms; Y is alkylene of 1 to 3 carbon atoms or alkenylene of 2 to 3 carbon atoms; n is one of the integers 0 to 1; m is one of the integers 2, 3, 4 or 5; R is phenyl, halophenyl, trifluoromethylphenyl, alkoxyphenyl in which the alkoxy substituent contains 1 to 3 carbon atoms, 2-pyrimidinyl, halopyrimidin-2-yl, 2-pyrazinyl, halopyrazin-2-yl, 2-pyridinyl, cyanopyridin-2-yl, halopyridin-2-yl, quinolyl, or haloquinolyl; or a pharmaceutically acceptable salt thereof.

  以下公式中的替代酰亚胺是抗精神病、抗焦虑剂，具有非常少的锥体外系副作用：##STR1## 其中X为--O--，--S--，--SO--，--SO.sub.2--，--CR.sub.3R.sub.4--，其中R.sub.3和R.sub.4独立地为氢、1到4个碳原子的烷基或与它们连接的碳原子形成3到5个碳原子的环烷基；Y为1到3个碳原子的烷基或2到3个碳原子的烯基烷基；n为0到1之间的整数；m为2、3、4或5之一的整数；R为苯基、卤代苯基、三氟甲基苯基、取代基含有1到3个碳原子的烷氧基苯基、2-嘧啶基、卤代2-嘧啶-2-基、2-吡嗪基、卤代2-吡嗪-2-基、2-吡啶基、氰基2-吡啶-2-基、卤代2-吡啶-2-基、喹啉基或卤代喹啉基；或其药学上可接受的盐。
• Psychotropic polycyclic imides
  申请人：AMERICAN HOME PRODUCTS CORPORATION

  公开号：EP0286263B1

  公开（公告）日：1991-05-15
• 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：——
• PSYCHOTROPIC BICYCLIC IMIDES
  申请人：AMERICAN HOME PRODUCTS CORPORATION

  公开号：EP0309544A1

  公开（公告）日：1989-04-05