1-[2-(2-Ethoxy-phenyl)-1-phenyl-ethyl]-piperazine | 860302-52-9

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 二苯乙烯类
• 英文名称: 1-[2-(2-Ethoxy-phenyl)-1-phenyl-ethyl]-piperazine
• 英文别名: 1-[2-(2-ethoxyphenyl)-1-phenylethyl]piperazine
• CAS: 860302-52-9
• 化学式: C₂₀H₂₆N₂O
• 分子量: 310.439
• InChiKey: CVFBVSUFNWOPLD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  23
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  24.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-[2-(2-Ethoxy-phenyl)-1-phenyl-ethyl]-piperazine 在 盐酸 作用下， 以 乙醚 为溶剂， 生成 (-)-1-[2-(2-ethoxyphenyl)-1-phenylethyl]piperazine dihydrochloride
  参考文献：
  名称：

  [EN] PIPERAZINE DERIVATIVES WHICH EXHIBIT ACTIVITY AS SEROTONIN AND NORADRENALINE RE-UPATKE INHIBITORS
  [FR] DERIVES DE LA PIPERAZINE PRESENTANT UNE ACTIVITE EN TANT QU'INHIBITEURS DU RECAPTAGE DE LA SEROTONINE ET DE LA NORADRENALINE

  摘要：

  式（I）的化合物，其中R1为H；R2为芳基，杂环基，C3-8环烷基，C1-6烷基，（CH2）z芳基或R4，其中每个环烷基，芳基，杂环基和R4基团可以选择地被至少一个取自C1-6烷基，C1-6甲氧基，OH，卤素，CF3，OCF3，OCHF2，O(CH2)yCF3，CN，CONH2，CON(H)C1-6烷基，CON(C1-6烷基)2，羟基-C1-6烷基，Cl-4烷氧基-C1-6烷基，C1-4烷氧基-C1-4烷氧基，SCF3，C1-6烷基ISO2，C1-4烷基-S-Cl-4烷基，C1-4烷基-S-，C1-4烷基NR10R11和NR10R11；或者R1和R2，连同它们结合的碳原子，形成一个含有至少一个N，O或S杂原子的5-或6元碳环或5-或6元杂环；R3为芳基，杂环基或R4，每个可以选择地被至少一个取自C1-6烷基，C1-6甲氧基，杂环基，OH，卤素，CF3，OCF3，OCHF2，O(CH2)yCF3，CN，CONH2，CON(H)C1-6烷基，CON(C1-6烷基)2，羟基-C1-6烷基，C1-4烷氧基-C1-6烷基，C1-4烷氧基-C1-4烷氧基，SCF3，C1-6烷基ISO2，C1-4烷基-S-C1-4烷基，C1-4烷基-S-，C1-4烷基NR10R11和NR10R11；R4为与一个含有至少一个N，O或S杂原子的5-或6元碳环融合的苯基，或者与一个含有至少一个N，O或S杂原子的5-或6元杂环融合的苯基；R5为H或C1-6烷基；R10和R11相同或不同且独立地为H或C1-4烷基；A为C1-3烷基链，可以选择地被OH，C1-4烷基或C1-4甲氧基取代；x为1到3的整数；y为1或2；z为1到3的整数；芳基为苯基，萘基，蒽基或菲基；杂环基为含有至少一个N，O或S杂原子的芳香或非芳香4-，5-或6元杂环，可以选择地与一个含有至少一个N，O或S杂原子的5-或6元碳环或第二个含有至少一个N，O或S杂原子的4-，5-或6元杂环融合。

  公开号：

  WO2005068447A1
• 作为产物：
  描述：

  1-tert-butyl 4-[1H-1,2,3-benzotriazol-1-yl (phenyl) methyl]piperazine-1-carboxylate 在 三氟乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 生成 1-[2-(2-Ethoxy-phenyl)-1-phenyl-ethyl]-piperazine
  参考文献：
  名称：

  N-(1,2-Diphenylethyl)piperazines: A new class of dual serotonin/noradrenaline reuptake inhibitor

  摘要：

  The synthesis and structure-activity relationships of a novel series of piperazine derivatives as dual inhibitors of serotonin and noradrenaline reuptake is described. Two compounds possessed comparable in vitro profiles to the dual reuptake inhibitor duloxetine. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2006.05.051

文献信息

• Structure–activity relationships of N-substituted piperazine amine reuptake inhibitors
  作者：M. Jonathan Fray、Gerwyn Bish、Paul V. Fish、Alan Stobie、Florian Wakenhut、Gavin A. Whitlock

  DOI：10.1016/j.bmcl.2006.05.049

  日期：2006.8

  We report the structure-activity relationships of further analogues in a series of piperazine derivatives as dual inhibitors of serotonin and noradrenaline reuptake, that is, with additional substitution of the phenyl rings, or their replacement by heterocycles. The enantiomers of compounds 1 and 2 were also profiled, and possessed drug-like physicochemical properties. In particular, compound (-)-2

  我们报告了一系列哌嗪衍生物作为5-羟色胺和去甲肾上腺素再摄取的双重抑制剂，即与苯环的其他取代或被杂环取代的双重抑制剂，在其他类似物之间的构效关系。还对化合物1和2的对映异构体进行了分析，并具有类似药物的理化性质。特别是，化合物（-）-2对任何重要的细胞色素P（450）均缺乏有效的抑制活性，并且在广泛的受体上缺乏高选择性，这对于抑制人类胺转运蛋白的化合物而言是罕见的。
• Piperazine derivatives which exhibit activity as serotonin and noradrenaline re-uptake inhibitors
  申请人：Bish Gerwyn

  公开号：US20070105870A1

  公开（公告）日：2007-05-10

  A compound of formula (I), wherein R 1 is H; R 2 is aryl, het, C 3-8 cycloalkyl, C 1-6 alkyl, (CH 2 ) 2 aryl or R 4 , wherein each of the cycloalkyl, aryl, het and R 4 groups is optionally substituted by at least one substituent independently selected from C 1-6 alkyl, C 1-6 alkoxy, OH, halo, CF 3 , OCF 3 , OCHF 2 , O(CH 2 ) y CF 3 , CN, CONH 2 , CON(H)C 1-6 alkyl, CON(C 1-6 alkyl) 2 , hydroxy-C 1-6 alkyl, C 1-4 alkoxy-C 1-6 alkyl, C 1-4 alkoxy-C 1-4 alkoxy, SCF 3 , C 1-6 alkyISO 2 , C 1-4 alkyl-S-C 1-4 alkyl, C 1-4 alkyl-S—, C 1-4 alkyINR 10 R 11 and NR 10 R 11 ; or R 1 and R 2 , together with the carbon atom to which they are bound, form a 5- or 6-membered carbocycle or a 5- or 6-membered heterocycle containing at least one N, O or S heteroatom; R 3 is aryl, het or R 4 , each optionally substituted by at least one substituent independently selected from C 1-6 -alkyl, C 1-6 -alkoxy, het, OH, halo, CF 3 , OCF 3 , OCHF 2 , O(CH 2 ) y CF 3 , CN, CONH 2 , CON(H)C 1-6 alkyl, CON(C 1-6 alkyl) 2 , hydroxy-C 1-6 alkyl, C 1-4 alkoxy-C 1-6 alkyl, C 1-4 alkoxy-C 1-4 alkoxy, SCF 3 , C 1-6 alkyISO 2 , C 1-4 alkyl-S-C 1-4 alkyl, C 1-4 alkyl-S—, C 1-4 alkylNR 10 R 11 and NR 10 R 11 ; R 4 is a phenyl group fused to a 5- or 6 membered carbocycle, or a phenyl group fused to a 5- or 6-membered heterocycle containing at least one N, O or S heteroatom; R 5 is H or C 1-6 alkyl; R 10 and R 11 are the same or different and are independently H or C 1-4 alkyl; A is a C 1-3 alkylene chain which is optionally substituted by OH, C 1-4 alkyl or C 1-4 alkoxy; x is an integer from 1 to 3; y is 1 or 2; z is an integer from 1 to 3; aryl is phenyl, naphthyl, anthracyl or phenanthryl; and het is an aromatic or non-aromatic 4, 5- or 6-membered heterocycle which contains at least one N, O or S heteroatom, optionally fused to a 5- or 6-membered carbocycle or a second 4, 5- or 6-membered heterocycle which contains at least one N, O or S heteroatom.

  化合物的化学式为（I），其中R1为H; R2为芳基，杂环，C3-8环烷基，C1-6烷基，（CH2）2芳基或R4，其中环烷基，芳基，杂环和R4基团中的每一个都可以独立地被至少一个取代基取代，所述取代基从C1-6烷基，C1-6烷氧基，OH，卤素，CF3，OCF3，OCHF2，O（CH2）yCF3，CN，CONH2，CON（H）C1-6烷基，CON（C1-6烷基）2，羟基-C1-6烷基，C1-4烷氧基-C1-6烷基，C1-4烷氧基-C1-4烷氧基，SCF3，C1-6烷基ISO2，C1-4烷基-S-C1-4烷基，C1-4烷基-S-，C1-4烷基INR10R11和NR10R11中独立选择; 或者R1和R2与它们所连接的碳原子一起形成一个含有至少一个N，O或S杂原子的5-或6-成员碳环或5-或6-成员杂环; R3为芳基，杂环或R4，每个都可以独立地被至少一个取代基取代，所述取代基从C1-6烷基，C1-6烷氧基，杂环，OH，卤素，CF3，OCF3，OCHF2，O（CH2）yCF3，CN，CONH2，CON（H）C1-6烷基，CON（C1-6烷基）2，羟基-C1-6烷基，C1-4烷氧基-C1-6烷基，C1-4烷氧基-C1-4烷氧基，SCF3，C1-6烷基ISO2，C1-4烷基-S-C1-4烷基，C1-4烷基-S-，C1-4烷基NR10R11和NR10R11中独立选择; R4是融合到5-或6-成员碳环中的苯基或融合到至少一个N，O或S杂原子的5-或6-成员杂环中的苯基; R5为H或C1-6烷基; R10和R11相同或不同，独立地为H或C1-4烷基; A为C1-3烷基链，可以选择地被OH，C1-4烷基或C1-4烷氧基取代; x为1到3的整数; y为1或2; z为1到3的整数; 芳基为苯基，萘基，蒽基或菲基; 杂环为含有至少一个N，O或S杂原子的芳香或非芳香4、5-或6-成员杂环，可以选择地融合到一个5-或6-成员碳环或第二个含有至少一个N，O或S杂原子的4、5-或6-成员杂环中。
• PIPERAZINE DERIVATIVES WHICH EXHIBIT ACIVITY AS SEROTONIN AND NORADRENALINE RE-UPATKE INHIBITORS
  申请人：Pfizer Limited

  公开号：EP1716129A1

  公开（公告）日：2006-11-02
• [EN] PIPERAZINE DERIVATIVES WHICH EXHIBIT ACTIVITY AS SEROTONIN AND NORADRENALINE RE-UPATKE INHIBITORS<br/>[FR] DERIVES DE LA PIPERAZINE PRESENTANT UNE ACTIVITE EN TANT QU'INHIBITEURS DU RECAPTAGE DE LA SEROTONINE ET DE LA NORADRENALINE
  申请人：PFIZER LTD

  公开号：WO2005068447A1

  公开（公告）日：2005-07-28

  A compound of formula (I), wherein R1 is H; R2 is aryl, het, C3-8cycloalkyl, C1-6alkyl, (CH2)zaryl or R4, wherein each of the cycloalkyl, aryl, het and R4 groups is optionally substituted by at least one substituent independently selected from C1-6alkyl, C1-6alkoxy, OH, halo, CF3, OCF3, OCHF2, O(CH2)yCF3, CN, CONH2, CON(H)C1-6alkyl, CON(C1-6alkyl)2, hydroxy-C1-6alkyl, Cl-4alkoxy-C1-6alkyl, C1-4alkoxy-C1-4alkoxy, SCF3, C1-6alkyISO2, C1-4alkyl-S-Cl-4alkyl, C1-4alkyl-S-, C1-4alkyINR10R11 and NR10R11; or R1 and R2, together with the carbon atom to which they are bound, form a 5- or 6-membered carbocycle or a 5- or 6-membered heterocycle containing at least one N, O or S heteroatom; R3 is aryl, het or R4, each optionally substituted by at least one substituent independently selected from C1-6alkyl, C1-6alkoxy, het, OH, halo, CF3, OCF3, OCHF2, O(CH2)yCF3, CN, CONH2, CON(H)C1-6alkyl, CON(C1-6alkyl)2, hydroxy-Cl-6alkyl, C1-4alkoxy-C1-6alkyl, C1-4alkoxy-C1-4 alkoxy, SCF3, C1-6alkyISO2, C1-4alkyl-S-C1-4alkyl, C1-4alkyl-S-, C1-4 alkylNR10R11and NR10R11; R4 is a phenyl group fused to a 5- or 6­ membered carbocycle, or a phenyl group fused to a 5- or 6-membered heterocycle containing at least one N, O or S heteroatom; R5 is H or C1- 6alkyl; R10 and R11 are the same or different and are independently H or C1-4alkyl; A is a C1-3alkylene chain which is optionally substituted by OH, C1-4alkyl or C1-4alkoxy; x is an integer from 1 to 3; y is 1 or 2; z is an integer from 1 to 3; aryl is phenyl, naphthyl, anthracyl or phenanthryl; and het is an aromatic or non-aromatic 4-, 5- or 6-membered heterocycle which contains at least one N, O or S heteroatom, optionally fused to a 5- ­or 6-membered carbocycle or a second 4-, 5- or 6-membered heterocycle which contains at least one N, O or S heteroatom.

  式（I）的化合物，其中R1为H；R2为芳基，杂环基，C3-8环烷基，C1-6烷基，（CH2）z芳基或R4，其中每个环烷基，芳基，杂环基和R4基团可以选择地被至少一个取自C1-6烷基，C1-6甲氧基，OH，卤素，CF3，OCF3，OCHF2，O(CH2)yCF3，CN，CONH2，CON(H)C1-6烷基，CON(C1-6烷基)2，羟基-C1-6烷基，Cl-4烷氧基-C1-6烷基，C1-4烷氧基-C1-4烷氧基，SCF3，C1-6烷基ISO2，C1-4烷基-S-Cl-4烷基，C1-4烷基-S-，C1-4烷基NR10R11和NR10R11；或者R1和R2，连同它们结合的碳原子，形成一个含有至少一个N，O或S杂原子的5-或6元碳环或5-或6元杂环；R3为芳基，杂环基或R4，每个可以选择地被至少一个取自C1-6烷基，C1-6甲氧基，杂环基，OH，卤素，CF3，OCF3，OCHF2，O(CH2)yCF3，CN，CONH2，CON(H)C1-6烷基，CON(C1-6烷基)2，羟基-C1-6烷基，C1-4烷氧基-C1-6烷基，C1-4烷氧基-C1-4烷氧基，SCF3，C1-6烷基ISO2，C1-4烷基-S-C1-4烷基，C1-4烷基-S-，C1-4烷基NR10R11和NR10R11；R4为与一个含有至少一个N，O或S杂原子的5-或6元碳环融合的苯基，或者与一个含有至少一个N，O或S杂原子的5-或6元杂环融合的苯基；R5为H或C1-6烷基；R10和R11相同或不同且独立地为H或C1-4烷基；A为C1-3烷基链，可以选择地被OH，C1-4烷基或C1-4甲氧基取代；x为1到3的整数；y为1或2；z为1到3的整数；芳基为苯基，萘基，蒽基或菲基；杂环基为含有至少一个N，O或S杂原子的芳香或非芳香4-，5-或6元杂环，可以选择地与一个含有至少一个N，O或S杂原子的5-或6元碳环或第二个含有至少一个N，O或S杂原子的4-，5-或6元杂环融合。
• N-(1,2-Diphenylethyl)piperazines: A new class of dual serotonin/noradrenaline reuptake inhibitor
  作者：M. Jonathan Fray、Gerwyn Bish、Alan D. Brown、Paul V. Fish、Alan Stobie、Florian Wakenhut、Gavin A. Whitlock

  DOI：10.1016/j.bmcl.2006.05.051

  日期：2006.8

  The synthesis and structure-activity relationships of a novel series of piperazine derivatives as dual inhibitors of serotonin and noradrenaline reuptake is described. Two compounds possessed comparable in vitro profiles to the dual reuptake inhibitor duloxetine. (c) 2006 Elsevier Ltd. All rights reserved.