2-苯乙基哌嗪 | 91907-37-8

• 分子结构分类: 有机化合物 - 有机氮化合物
• 中文名称: 2-苯乙基哌嗪
• 英文名称: 2-Phenethylpiperazine
• 英文别名: 2-(2-phenylethyl)piperazine
• CAS: 91907-37-8
• 化学式: C₁₂H₁₈N₂
• mdl: MFCD07373378
• 分子量: 190.28
• InChiKey: FRTXUSHWBSBIAT-UHFFFAOYSA-N

物化性质

• 沸点：
  313.7±17.0 °C(Predicted)
• 密度：
  0.966±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  14
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  24.1
• 氢给体数：
  2
• 氢受体数：
  2

安全信息

• 危险等级：
  IRRITANT
• 海关编码：
  2933599090

反应信息

• 作为产物：
  描述：

  1,4-dibenzyl-2-styryl-piperazine 在 氢氧化钯 氢气 、 氢氧化钯 、 silica gel 作用下， 以 乙醇 为溶剂， 25.0~60.0 ℃ 、55.15 MPa 条件下， 反应 24.0h， 生成 2-苯乙基哌嗪
  参考文献：
  名称：

  Piperazine substituted aryl benzodiazepines and their use as dopamine receptor antagonists for the treatment of psychotic disorders

  摘要：

  本文描述了式(I)的抗精神病化合物，其中，A是可选择与苯融合的五元或六元芳香环，其中独立选择0至3个杂原子，包括N、O和S；Alk是(C1-4)烷基，可选地带有OH、甲氧基、乙氧基或F基；Ar是可选取代的苯基、萘基、单环杂芳基或双环杂芳基；R1是氢或(C1-4)烷基，可选地带有OH、OR3或OCH2CH2OH，其中R3是(C1-2)烷基；R2是H、(C1-6)烷基、卤素、氟代(C1-6)烷基、OR4、SR4、NO2、CN、COR4、CONR5R6、SO2NR5R6、NR5R6、NR5COR4、NR5SO2R4或可选取代的苯基，其中R4是氢、(C1-6)烷基、氟代(C1-6)烷基或可选取代的苯基，R5和R6独立选择氢、(C1-6)烷基或可选取代的苯基；Z是一个或两个取代基，独立选择氢、卤素、(C1-6)烷基、氟代(C1-6)烷基、OR7、SR7、NO2、CN、COR7、CONR8R9、SO2NR8R9、NR8SO2R7、NR8R9或可选取代的苯基，其中R7是氢、(C1-6)烷基、氟代烷基或可选取代的苯基，R8和R9独立选择氢、(C1-6)烷基或可选取代的苯基；以及其盐、溶剂化物和晶体形式。还描述了式(I)化合物作为多巴胺D2受体拮抗剂和治疗精神病和双相情感障碍的药物，以及式(I)化合物的制剂。

  公开号：

  US07214673B2

文献信息

• [EN] SUBSTITUTED PIPERAZINES OF AZEPINES, OXAZEPINES, AND THIAZEPINES<br/>[FR] PIPERAZINES SUBSTITUTEES D'AZEPINES, D'OXAZEPINES, ET DE THIAZEPINES
  申请人：LILLY CO ELI

  公开号：WO2005026177A1

  公开（公告）日：2005-03-24

  Described herein are antipyschotic compounds of formula (I) wherein: is an optionally benzo-fused five or six member aromatic ring having zero to three hetero atoms independently selected from N, O, and S; R1 is hydrogen, (C1-6) fluoroalkyl, (C3-6) cycloalkyl, or (C1-4) alkyl, wherein the (C1-4) alkyl is unsubstituted or substituted with hydroxy, methoxy, ethoxy, OCH2CH2OH, -CN, imidazolidin-2-one, phenyl, or tetrazole wherein tetrazole is unsubstituted or substituted with (C1-4) alkyl; R2 is H, halogen, (C1-6) fluoroalkyl, (C3-6) cycloalkyl, OR6, SR6, NO2, CN, COR6, C(O)OR6, C(OH)R6, CONR7R8, phenyl or (C1-6) alkyl, wherein the (C1-6) alkyl is unsubstituted or substituted with a hydroxy; R3 is hydrogen, (C 1-6)fluoroalkyl , (C3-6) cycloalkyl, (C 2-6) alkenyl, phenyl, monocyclic heteroaromatic, bicyclic heteroaromatic, or (C1-4)alkyl wherein (C1-4) alkyl is unsubstituted or substituted with a phenyl; R4 and R5 are independently selected from hydrogen, halogen, (C1-6) alkyl, (C1-6) fluoroalkyl, OR9, SR9, NO2, CN, or COR9; R6 is hydrogen, (C1-6) fluoroalkyl, or (C1-6) alkyl; R7 and R8 are independently hydrogen, or (C1-6) alkyl; R9 is hydrogen, (C1-6) fluoroalkyl, (C1-6) alkyl; Alk is (C1-4) alkylene unsubstituted or substituted with a hydroxy; Y is oxygen, sulfur, SO2, or a bond; X is CH2, C=O, S, O, or SO2; Z is hydrogen, halogen, (C1-6) alkyl, (C1-6)fluoroalkyl, -OH, (C1-6) alkoxy, (C1-6) fluoroalkoxy, (C1-6) alkylthio, (C1-6) acyl, (C1-4)alkylsulfonyl, -OCF3, -NO2, - CN, carboxamido which may be substituted on the nitrogen by one or two (C1-4) alkyl groups, and -NH2 in which one of the hydrogens may be replaced by a (C1-4) alkyl group and the other hydrogen may be replaced by either a (C1-4) alkyl group, a (C1-6) acyl group, or a (C1-4) alkylsulfonyl group; the phenyl of R1, R2 or R3 is independently unsubstituted or substituted with one to three substituents independently selected from Z; the monocyclic heteroaromatic of R3 is unsubstituted or substituted with one to three substituents independently selected from Z; the bicyclic heteroaromatic of R3 is unsubstituted or substituted with one to three substituents independently selected from Z; and salts, solvates, and crystal forms thereof. Also described are the use of the compounds of formula (I) as antagonists of the dopamine D2 receptor and as agents for the treatment of psychosis and bipolar disorders, and pharmaceutical formulations of the compounds of formula (I).

  本文描述了式(I)的抗精神病化合物，其中：是一个可选的苯并五元或六元芳香环，其中含有零至三个异原子，独立选择自N、O和S；R1是氢，(C1-6)氟烷基，(C3-6)环烷基，或(C1-4)烷基，其中(C1-4)烷基未取代或取代为羟基、甲氧基、乙氧基、O OH、-CN、咪唑烷-2-酮、苯基或四氮唑，其中四氮唑未取代或取代为(C1-4)烷基；R2是H、卤素、(C1-6)氟烷基、(C3-6)环烷基、OR6、SR6、NO2、CN、COR6、C(O)OR6、C(OH)R6、CONR7R8、苯基或(C1-6)烷基，其中(C1-6)烷基未取代或取代为羟基；R3是氢，(C1-6)氟烷基，(C3-6)环烷基，(C2-6)烯基，苯基，单环杂芳基，双环杂芳基，或(C1-4)烷基，其中(C1-4)烷基未取代或取代为苯基；R4和R5独立选择自氢、卤素、(C1-6)烷基、(C1-6)氟烷基、OR9、SR9、 、CN或COR9；R6是氢、(C1-6)氟烷基或(C1-6)烷基；R7和R8独立选择自氢或(C1-6)烷基；R9是氢、(C1-6)氟烷基或(C1-6)烷基；Alk是未取代或取代为羟基的(C1-4)烷基；Y是氧、硫、SO2或键；X是CH2、C=O、S、O或SO2；Z是氢、卤素、(C1-6)烷基、(C1-6)氟烷基、-OH、(C1-6)烷氧基、(C1-6)氟烷氧基、(C1-6)烷硫基、(C1-6)酰基、(C1-4)烷基磺酰基、-OCF3、- 、-CN、羧酰胺基，该羧酰胺基可在氮上被一个或两个(C1-4)烷基取代，以及-NH2，其中一个氢原子可被(C1-4)烷基取代，另一个氢原子可被(C1-4)烷基、(C1-6)酰基或(C1-4)烷基磺酰基取代；R1、R2或R3的苯基独立地未取代或取代为从Z中独立选择的一个至三个取代基；R3的单环杂芳基未取代或取代为从Z中独立选择的一个至三个取代基；R3的双环杂芳基未取代或取代为从Z中独立选择的一个至三个取代基；以及其盐、溶剂化合物和晶型形式。还描述了将式(I)的化合物用作多巴胺D2受体拮抗剂和治疗精神病和双相情感障碍的药物，以及式(I)的药物配方。
• [EN] PIPERAZINE SUBSTITUTED ARYL BENZODIAZEPINES AND THEIR USE AS DOPAMINE RECEPTOR ANTAGONISTS FOR THE TREATMENT OF PSYCHOTIC DISORDERS<br/>[FR] ARYLES BENZODIAZEPINES A SUBSTITUTION DE PIPERAZINE ET LEUR UTILISATION EN TANT QU'ANTAGONISTES DE RECEPTEUR DE DOPAMINE DANS LE TRAITEMENT DE TROUBLES PSYCHOTIQUES
  申请人：LILLY CO ELI

  公开号：WO2003082877A1

  公开（公告）日：2003-10-09

  Described herein are antipyschotic compounds of formula (I) wherein, A is an optionally benzo-fused five or six member aromatic ring having zero to three hetero atoms independently selected from N, O, and S; Alk is (C1-4) alkylene optionally substituted with OH, methoxy, ethoxy, or F; Ar is optionally substituted phenyl, naphthyl, monocyclic heteroaromatic, or bicyclic heteroaromatic; R1 is hydrogen or (C1-4) alkyl optionally substituted with OH, OR3, or OCH2CH2OH, wherein R3 is (C1-2) alkyl; R2 is H, (C1-6) alkyl, halogen, fluorinated (C1-6) alkyl, OR4, SR4, NO2, CN, COR4, CONR5R6, SO2NR5R6, NR5R6, NR5COR4, NR5SO2R4, or optionally substituted phenyl,wherein R4 is hydrogen, (C1-6) alkyl, fluorinated (C1-6) alkyl, benzyl, or optionally substituted phenyl, R5 and R6 are independently hydrogen, (C1-6) alkyl, or optionally substituted phenyl; Z is one or two substituents independently selected from hydrogen, halogen, (C1-6) alkyl, fluorinated (C1-6) alkyl, OR7, SR7, NO2, CN, COR7, CONR8R9, SO2NR8R9, NR8SO2R7, NR8R9, or optionally substituted phenyl, wherein R7 is hydrogen, (C1-6) alkyl, fluorinated (C1-6) alkyl, benzyl, or optionally substituted phenyl, R8 and R9 are independently hydrogen, (C1-6) alkyl, or optionally substituted phenyl; and salts, solvates, and crystal forms thereof. Also described are the use of the compounds of formula (I) as antagonists of the dopamine D2 receptor and as agents for the treatment of psychosis and bipolar disorders, and pharmaceutical formulations of the compounds of formula (I). Also described are compounds useful as intermediates for the synthesis of the compounds of formula (I).

  本文描述了公式（I）的抗精神药物化合物，其中，A是一个可选的苯并嵌有零至三个异原子（N、O和S）的五元或六元芳香环；Alk是（C1-4）烷基烯，可选地取代为OH、甲氧基、乙氧基或F；Ar是可选取代的苯基、萘基、单环杂芳基或双环杂芳基；R1是氢或（C1-4）烷基，可选地取代为OH、OR3或OCH2CH2OH，其中R3是（C1-2）烷基；R2是H、（C1-6）烷基、卤素、氟代（C1-6）烷基、OR4、SR4、NO2、CN、COR4、CONR5R6、SO2NR5R6、NR5R6、NR5COR4、NR5SO2R4或可选取代的苯基，其中R4是氢、（C1-6）烷基、氟代（C1-6）烷基、苄基或可选取代的苯基，R5和R6独立地是氢、（C1-6）烷基或可选取代的苯基；Z是一个或两个取代基，独立地选自氢、卤素、（C1-6）烷基、氟代（C1-6）烷基、OR7、SR7、 、CN、COR7、CONR8R9、SO2NR8R9、NR8SO2R7、NR8R9或可选取代的苯基，其中R7是氢、（C1-6）烷基、氟代（C1-6）烷基、苄基或可选取代的苯基，R8和R9独立地是氢、（C1-6）烷基或可选取代的苯基；以及其盐、溶剂合物和晶型。还描述了将公式（I）的化合物用作多巴胺D2受体拮抗剂和治疗精神病和双相障碍的药物，以及公式（I）的化合物的制剂。还描述了作为公式（I）化合物合成的中间体有用的化合物。
• Use of N-benzyl piperazine and analogues as quality of life enhancers
  申请人：——

  公开号：US20020156084A1

  公开（公告）日：2002-10-24

  A chemical composition, namely n-benzyl piperazine and derivatives, for use as a weight control product and or a quality of life enhancer. The unobviousness lies in the fact that the aforementioned compounds work without the unwanted side effects of many weight control products, due to their “harmonious” balancing of the norepinephrine and serotonin receptors in the brain.

  一种化学组合物，即n-苄基哌嗪及其衍生物，用作减重产品或生活质量增强剂。其非显而易见之处在于上述化合物在大脑内通过“和谐”平衡去甲肾上腺素和5-羟色胺受体的作用而无需担心许多减重产品的不良副作用。
• Substituted piperazines of azepines, oxazepines and thiazepines
  申请人：He Xiaoqiang John

  公开号：US20060270656A1

  公开（公告）日：2006-11-30

  Described herein are antipyschotic compounds of formula (I) wherein: is an optionally benzo-fused five or six member aromatic ring having zero to three hetero atoms independently selected from N, O, and S; R 1 is hydrogen, (C 1-6 ) fluoroalkyl, (C 3-6 ) cycloalkyl, or (C 1-4 ) alkyl, wherein the (C 1-4 ) alkyl is unsubstituted or substituted with hydroxy, methoxy, ethoxy, OCH 2 CH 2 OH, —CN, imidazolidin-2-one, phenyl, or tetrazole wherein tetrazole is unsubstituted or substituted with (C 1-4 ) alkyl; R 2 is H, halogen, (C 1-6 ) fluoroalkyl, (C 3-6 ) cycloalkyl, OR 6 , SR 6 , NO 2 , CN, COR 6 , C(O)OR 6 , C(OH)R 6 , CONR 7 R 8 , phenyl or (C 1-6 ) alkyl, wherein the (C 1-6 ) alkyl is unsubstituted or substituted with a hydroxy; R 3 is hydrogen, (C 1-6 )fluoroalkyl , (C 3-6 ) cycloalkyl, (C 2-6 ) alkenyl, phenyl, monocyclic heteroaromatic, bicyclic heteroaromatic, or (C 1-4 )alkyl wherein (C 1-4 ) alkyl is unsubstituted or substituted with a phenyl; R 4 and R 5 are independently selected from hydrogen, halogen, (C 1-6 ) alkyl, (C 1-6 ) fluoroalkyl, OR 9 , SR 9 , NO 2 , CN, or COR 9 ; R 6 is hydrogen, (C 1-6 ) fluoroalkyl, or (C 1-6 ) alkyl; R 7 and R 8 are independently hydrogen, or (C 1-6 ) alkyl; R 9 is hydrogen, (C 1-6 ) fluoroalkyl, (C 1-6 ) alkyl; Alk is (C 1-4 ) alkylene unsubstituted or substituted with a hydroxy; Y is oxygen, sulfur, SO 2 , or a bond; X is CH 2 , C═O, S, O, or SO 2 ; Z is hydrogen, halogen, (C 1-6 ) alkyl, (C 1-6 )fluoroalkyl, —OH, (C 1-6 ) alkoxy, (C 1-6 ) fluoroalkoxy, (C 1-6 ) alkylthio, (C 1-6 ) acyl, (C 1-4 )alkylsulfonyl, —OCF 3 , —NO 2 , —CN, carboxamido which may be substituted on the nitrogen by one or two (C 1-4 ) alkyl groups, and —NH 2 in which one of the hydrogens may be replaced by a (C 1-4 ) alkyl group and the other hydrogen may be replaced by either a (C 1-4 ) alkyl group, a (C 1-6 ) acyl group, or a (C 1-4 ) alkylsulfonyl group; the phenyl of R 1 , R 2 or R 3 is independently unsubstituted or substituted with one to three substituents independently selected from Z; the monocyclic heteroaromatic of R 3 is unsubstituted or substituted with one to three substituents independently selected from Z; the bicyclic heteroaromatic of R 3 is unsubstituted or substituted with one to three substituents independently selected from Z; and salts, solvates, and crystal forms thereof. Also described are the use of the compounds of formula (I) as antagonists of the dopamine D 2 receptor and as agents for the treatment of psychosis and bipolar disorders, and pharmaceutical formulations of the compounds of formula (I).

  本文描述了式(I)的抗精神病化合物，其中： - 是一个可选的苯并五元或六元芳香环，其具有0-3个杂原子，独立地选自N，O和S； - R1是氢，(C1-6)氟烷基，(C3-6)环烷基或(C1-4)烷基，其中(C1-4)烷基未取代或取代了羟基，甲氧基，乙氧基，O OH，—CN，咪唑啉-2-酮，苯基或四唑，其中四唑未取代或取代了(C1-4)烷基； - R2是H，卤素，(C1-6)氟烷基，(C3-6)环烷基，OR6，SR6，NO2，CN，COR6，C(O)OR6，C(OH)R6，CONR7R8，苯基或(C1-6)烷基，其中(C1-6)烷基未取代或取代了羟基； - R3是氢，(C1-6)氟烷基，(C3-6)环烷基，(C2-6)烯基，苯基，单环杂芳基，双环杂芳基或(C1-4)烷基，其中(C1-4)烷基未取代或取代了苯基； - R4和R5独立地选自氢，卤素，(C1-6)烷基，(C1-6)氟烷基，OR9，SR9， ，CN或COR9； - R6是氢，(C1-6)氟烷基或(C1-6)烷基； - R7和R8独立地是氢或(C1-6)烷基； - R9是氢，(C1-6)氟烷基或(C1-6)烷基； - Alk是(C1-4)烷基，未取代或取代了羟基； - Y是氧，硫，SO2或键； - X是CH2，C═O，S，O或SO2； - Z是氢，卤素，(C1-6)烷基，(C1-6)氟烷基，—OH，(C1-6)烷氧基，(C1-6)氟烷氧基，(C1-6)烷硫基，(C1-6)酰基，(C1-4)烷基磺酰基，—OCF3，— ，—CN，羧酰胺，其氮上可能通过一个或两个(C1-4)烷基取代，以及—NH2，在其中一个氢可能被(C1-4)烷基取代，另一个氢可能被(C1-4)烷基，(C1-6)酰基或(C1-4)烷基磺酰基取代； - R1，R2或R3的苯基独立地未取代或取代了1-3个Z取代基； - R3的单环杂芳基未取代或取代了1-3个Z取代基； - R3的双环杂芳基未取代或取代了1-3个Z取代基； - 还描述了该化合物的盐，溶剂化合物和晶体形式。 还描述了将式(I)化合物用作多巴胺D2受体拮抗剂和治疗精神病和双相障碍的药物，以及式(I)化合物的制剂。
• Novel Heterocyclic Substituted Carbonyl Derivatives and Their Use as Dopamine D3 Receptor Ligands
  申请人：Hendrix James A.

  公开号：US20090247509A1

  公开（公告）日：2009-10-01

  The invention relates to heterocyclic substituted carbonyl derivatives that display selective binding to dopamine D 3 receptors. In another aspect, the invention relates to a method for treating central nervous system disorders associated with the dopamine D 3 receptor activity in a patient in need of such treatment comprising administering to the subject a therapeutically effective amount of said compounds for alleviation of such disorder. The central nervous system disorders that may be treated with these compounds include Psychotic Disorders, Substance Dependence, Substance Abuse, Dyskinetic Disorders (e.g. Parkinson's Disease, Parkinsonism, Neuroleptic-Induced Tardive Dyskinesia, Gilles de la Tourette Syndrome and Huntington's Disease), Dementia, Anxiety Disorders, Sleep Disorders, Circadian Rhythm Disorders and Mood Disorders. The subject invention is also directed towards processes for the preparation of the compounds described herein as well as methods for making and using the compounds as imaging agents for dopamine D 3 receptors.

  本发明涉及杂环取代羰基衍生物，其表现出对多巴胺D3受体的选择性结合。另一方面，本发明涉及一种治疗与多巴胺D3受体活性相关的中枢神经系统疾病的方法，该方法包括向需要此类治疗的患者施用所述化合物的治疗有效量，以缓解此类疾病。这些化合物可以治疗的中枢神经系统疾病包括精神疾病、物质依赖、物质滥用、运动障碍（例如帕金森病、帕金森综合症、神经阻滞引起的迟发性运动障碍、吉尔斯-德-拉-图雷综合症和亨廷顿病）、痴呆、焦虑症、睡眠障碍、昼夜节律紊乱和情绪障碍。本发明还涉及制备所述化合物的方法以及将所述化合物作为多巴胺D3受体成像剂的制备和使用方法。