3-[4-(8-chloro-5H-dibenzo[b,e][1,4]diazepin-11-yl)piperazin-1-yl]propan-1-amine | 1357146-50-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯二氮卓类
• 英文名称: 3-[4-(8-chloro-5H-dibenzo[b,e][1,4]diazepin-11-yl)piperazin-1-yl]propan-1-amine
• 英文别名: 3-[4-(3-chloro-11H-benzo[b][1,4]benzodiazepin-6-yl)piperazin-1-yl]propan-1-amine
• CAS: 1357146-50-9
• 化学式: C₂₀H₂₄ClN₅
• 分子量: 369.897
• InChiKey: WKAWHDXJLCGDAE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  26
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  56.9
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  癸二酰氯 、 3-[4-(8-chloro-5H-dibenzo[b,e][1,4]diazepin-11-yl)piperazin-1-yl]propan-1-amine 在 吡啶 作用下， 以 二氯甲烷 为溶剂， 以0.071 g的产率得到N1,N10-bis(3-(4-(8-chloro-5H-dibenzo[b,e][1,4]diazepin-11-yl)piperazin-1-yl)propyl)decanediamide
  参考文献：
  名称：

  Homobivalent Ligands of the Atypical Antipsychotic Clozapine: Design, Synthesis, and Pharmacological Evaluation

  摘要：

  To date all typical and atypical antipsychotics target the dopamine D-2 receptor. Clozapine represents the best-characterized atypical antipsychotic, although it displays only moderate (submicromolar) affinity for the dopamine D-2 receptor. Herein, we present the design, synthesis, and pharmacological evaluation of three series of homobivalent ligands of clozapine, differing in the length and nature of the spacer and the point of attachment to the pharmacophore. Attachment of the spacer at the N4' position of clozapine yielded a series of homobivalent ligands that displayed spacer-length-dependent gains in affinity and activity for the dopamine D-2 receptor. The 16 and 18 atom spacer bivalent ligands were the highlight compounds, displaying marked low nanomolar receptor binding affinity (1.41 and 1.35 nM, respectively) and functional activity (23 and 44 nM), which correspond to significant gains in affinity (75- and 79-fold) and activity (9- and 5-fold) relative to the original pharmacophore, clozapine. As such these ligands represent useful tools with which to investigate dopamine receptor dimerization and the atypical nature of clozapine.

  DOI：

  10.1021/jm201420s
• 作为产物：
  描述：

  8-氯-11-(1-哌嗪基)-5H-二苯并[B,E] [1,4]吡喃 在 N,N-二异丙基乙胺 、 三氟乙酸 、 sodium iodide 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 反应 5.0h， 生成 3-[4-(8-chloro-5H-dibenzo[b,e][1,4]diazepin-11-yl)piperazin-1-yl]propan-1-amine
  参考文献：
  名称：

  Homobivalent Ligands of the Atypical Antipsychotic Clozapine: Design, Synthesis, and Pharmacological Evaluation

  摘要：

  To date all typical and atypical antipsychotics target the dopamine D-2 receptor. Clozapine represents the best-characterized atypical antipsychotic, although it displays only moderate (submicromolar) affinity for the dopamine D-2 receptor. Herein, we present the design, synthesis, and pharmacological evaluation of three series of homobivalent ligands of clozapine, differing in the length and nature of the spacer and the point of attachment to the pharmacophore. Attachment of the spacer at the N4' position of clozapine yielded a series of homobivalent ligands that displayed spacer-length-dependent gains in affinity and activity for the dopamine D-2 receptor. The 16 and 18 atom spacer bivalent ligands were the highlight compounds, displaying marked low nanomolar receptor binding affinity (1.41 and 1.35 nM, respectively) and functional activity (23 and 44 nM), which correspond to significant gains in affinity (75- and 79-fold) and activity (9- and 5-fold) relative to the original pharmacophore, clozapine. As such these ligands represent useful tools with which to investigate dopamine receptor dimerization and the atypical nature of clozapine.

  DOI：

  10.1021/jm201420s

文献信息

• BROAD SPECTRUM GPCR BINDING AGENTS
  申请人：Promega Corporation

  公开号：US20200200765A1

  公开（公告）日：2020-06-25

  Provided herein are broad-spectrum G-Protein coupled receptor (GPCR) binding agents, detectable/isolatable compounds comprising such binding agents (e.g., broad-spectrum GPCR binding agents linked to a functional element and/or solid surface), and methods of use thereof for the detection/isolation of GPCRs.