1-{2-[2-(difluoromethoxy)-6-fluorophenyl]-1-phenylethyl}piperazine | 1238670-27-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 1-{2-[2-(difluoromethoxy)-6-fluorophenyl]-1-phenylethyl}piperazine
• 英文别名: 1-(2-(2-(Difluoromethoxy)-6-fluorophenyl)-1-phenylethyl)piperazine；1-[2-[2-(difluoromethoxy)-6-fluorophenyl]-1-phenylethyl]piperazine
• CAS: 1238670-27-3
• 化学式: C₁₉H₂₁F₃N₂O
• 分子量: 350.384
• InChiKey: FNRNKAMBXVROAU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  25
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  24.5
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 生成 1-{2-[2-(difluoromethoxy)-6-fluorophenyl]-1-phenylethyl}piperazine
  参考文献：
  名称：

  Second generation N-(1,2-diphenylethyl)piperazines as dual serotonin and noradrenaline reuptake inhibitors: Improving metabolic stability and reducing ion channel activity

  摘要：

  New N-(1,2-diphenylethyl)piperazines 6 are disclosed as dual serotonin and noradrenaline reuptake inhibitors (SNRI) which may have potential in treating stress urinary incontinence (SUI). In this Letter, we present new data for SNRI PF-526014 (4) including performance in a canine in vivo model of SUI, cardiovascular assessment, pharmacokinetics in dog and determination of the primary routes of metabolism in vitro. Starting from 4, detailed structure activity relationships established that potent dual SNRIs could be achieved by appropriate substitution of the phenyl rings (6: R; R-1) combined with a preferred stereochemistry. From this set of compounds, piperazine (-)-6a was identified as a potent and selective dual SNRI with improved metabolic stability and reduced ion channel activity when compared to 4. Based on this profile, (-)-6a was selected for further evaluation in a preclinical model of SUI. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.04.052

文献信息

• 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，O ，OCHF2，O（ ）y ，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，S ，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， ，O ，OCHF2，O（ ）y ，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，S ，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。