1-(4-bromobenzyl)-4-(2,3-dichlorophenyl)piperazine | 1354030-65-1

• 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: 1-(4-bromobenzyl)-4-(2,3-dichlorophenyl)piperazine
• 英文别名: 1-(4-Bromobenzyl)-4-(2,3-dichlorophenyl)piperazine；1-[(4-bromophenyl)methyl]-4-(2,3-dichlorophenyl)piperazine
• CAS: 1354030-65-1
• 化学式: C₁₇H₁₇BrCl₂N₂
• 分子量: 400.145
• InChiKey: DRLLRXFYHGLJEN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  6.5
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  3,4-二氢-7-羟基-2(1H)-喹啉酮 、 1-(4-bromobenzyl)-4-(2,3-dichlorophenyl)piperazine 在 2,2,6,6-四甲基-3,5-庚二酮 、 caesium carbonate 、 copper(l) chloride 作用下， 以 N-甲基吡咯烷酮 为溶剂， 反应 7.5h， 以35%的产率得到7-(4-((4-(2,3-dichlorophenyl)piperazin-1-yl)methyl)phenoxy)-3,4-dihydroquinolin-2(1H)-one
  参考文献：
  名称：

  Structure–Functional Selectivity Relationship Studies of β-Arrestin-Biased Dopamine D₂Receptor Agonists

  摘要：

  Functionally selective G protein-coupled receptor (GPCR) ligands, which differentially modulate canonical and noncanonical signaling, are extremely useful for elucidating key signal transduction pathways essential for both the therapeutic actions and side effects of drugs. However, few such ligands have been created, and very little purposeful attention has been devoted to studying what we term: "structure-functional selectivity relationships" (SFSR). We recently disclosed the first beta-arrestin-biased dopamine D-2 receptor (D2R) agonists UNC9975 (44) and UNC9994 (36), which have robust in vivo antipsychotic drug-like activities. Here we report the first comprehensive SFSR studies focused on exploring four regions of the aripiprazole scaffold, which resulted in the discovery of these beta-arrestin-biased D2R agonists. These studies provide a successful proof-of-concept for how functionally selective ligands can be discovered.

  DOI：

  10.1021/jm300603y
• 作为产物：
  描述：

  2,3-二氯溴苯 在 tris-(dibenzylideneacetone)dipalladium(0) 盐酸 、 R-(+)-1,1'-联萘-2,2'-双二苯膦 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 三乙胺 、 sodium t-butanolate 作用下， 以 乙酸乙酯 、 甲苯 、 乙腈 为溶剂， 反应 5.5h， 生成 1-(4-bromobenzyl)-4-(2,3-dichlorophenyl)piperazine
  参考文献：
  名称：

  [EN] FUNCTIONALLY SELECTIVE LIGANDS OF DOPAMINE D2 RECEPTORS
  [FR] LIGANDS FONCTIONNELLEMENT SÉLECTIFS DES RÉCEPTEURS D2 DE DOPAMINE

  摘要：

  公开号：

  WO2012003418A3
• 作为试剂：
  描述：

  1-(2,3-二氯苯基)哌嗪 、 对溴溴苄 、 三乙胺 在 乙酸乙酯 、 碳酸氢钠 、 Brine 、 Sodium sulfate-III 、 silica gel 、 1-(4-bromobenzyl)-4-(2,3-dichlorophenyl)piperazine 作用下， 以 乙腈 、 水 为溶剂， 反应 4.0h， 以to give 1-(4-bromobenzyl)-4-(2,3-dichlorophenyl)piperazine (intermediate 54) (220 mg, 74%) as a white solid的产率得到1-(4-bromobenzyl)-4-(2,3-dichlorophenyl)piperazine
  参考文献：
  名称：

  Novel Functionally Selective Ligands of Dopamine D2 Receptors

  摘要：

  本发明涉及多巴胺D2受体的新型功能选择性配体，包括激动剂、拮抗剂和反向激动剂，其中图1为配体结构。本发明还涉及使用这些化合物治疗与D2受体相关的中枢神经系统疾病。

  公开号：

  US20130137679A1

文献信息

• Functionally selective ligands of dopamine D2 receptors
  申请人：Jin Jian

  公开号：US09156822B2

  公开（公告）日：2015-10-13

  The present invention relates to novel functionally selective ligands of dopamine D2 receptors, including agonists, antagonists, and inverse agonists. The invention further relates to the use of these compounds for treating central nervous system disorders related to D2 receptors.

  本发明涉及多巴胺D2受体的新型功能选择性配体，包括激动剂、拮抗剂和反向激动剂。本发明还涉及使用这些化合物治疗与D2受体有关的中枢神经系统疾病。
• US9156822B2
  申请人：——

  公开号：US9156822B2

  公开（公告）日：2015-10-13
• Structure–Functional Selectivity Relationship Studies of β-Arrestin-Biased Dopamine D₂Receptor Agonists
  作者：Xin Chen、Maria F. Sassano、Lianyou Zheng、Vincent Setola、Meng Chen、Xu Bai、Stephen V. Frye、William C. Wetsel、Bryan L. Roth、Jian Jin

  DOI：10.1021/jm300603y

  日期：2012.8.23

  Functionally selective G protein-coupled receptor (GPCR) ligands, which differentially modulate canonical and noncanonical signaling, are extremely useful for elucidating key signal transduction pathways essential for both the therapeutic actions and side effects of drugs. However, few such ligands have been created, and very little purposeful attention has been devoted to studying what we term: "structure-functional selectivity relationships" (SFSR). We recently disclosed the first beta-arrestin-biased dopamine D-2 receptor (D2R) agonists UNC9975 (44) and UNC9994 (36), which have robust in vivo antipsychotic drug-like activities. Here we report the first comprehensive SFSR studies focused on exploring four regions of the aripiprazole scaffold, which resulted in the discovery of these beta-arrestin-biased D2R agonists. These studies provide a successful proof-of-concept for how functionally selective ligands can be discovered.
• [EN] FUNCTIONALLY SELECTIVE LIGANDS OF DOPAMINE D2 RECEPTORS<br/>[FR] LIGANDS FONCTIONNELLEMENT SÉLECTIFS DES RÉCEPTEURS D2 DE DOPAMINE
  申请人：UNIV NORTH CAROLINA

  公开号：WO2012003418A3

  公开（公告）日：2012-05-18
• Novel Functionally Selective Ligands of Dopamine D2 Receptors
  申请人：Jin Jian

  公开号：US20130137679A1

  公开（公告）日：2013-05-30

  The present invention relates to novel functionally selective ligands of dopamine D2 receptors, FIG. 1 including agonists, antagonists, and inverse agonists. The invention further relates to the use of these compounds for treating central nervous system disorders related to D2 receptors.

  本发明涉及多巴胺D2受体的新型功能选择性配体，包括激动剂、拮抗剂和反向激动剂，其中图1为配体结构。本发明还涉及使用这些化合物治疗与D2受体相关的中枢神经系统疾病。