2-[4-(4-phenylpiperazin-1-yl)butyl]isoindolin-1-one | 25557-39-5

• 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: 2-[4-(4-phenylpiperazin-1-yl)butyl]isoindolin-1-one
• 英文别名: 2-[4-(4-phenyl-piperazin-1-yl)-butyl]-2,3-dihydro-isoindol-1-one；2-[4-(4-phenylpiperazin-1-yl)butyl]-3H-isoindol-1-one
• CAS: 25557-39-5
• 化学式: C₂₂H₂₇N₃O
• 分子量: 349.476
• InChiKey: SEAGRPUHJMFFQR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  26
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  26.8
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-[4-(4-phenylpiperazin-1-yl)butyl]isoindolin-1-one 在 盐酸 作用下， 以 水 为溶剂， 生成 2-[4-(4-phenylpiperazin-1-yl)butyl]-2,3-dihydro-1H-isoindol-1-one dihydrochloride
  参考文献：
  名称：

  Synthesis of New Serotonin 5-HT₇ Receptor Ligands. Determinants of 5-HT₇/5-HT_1A Receptor Selectivity

  摘要：

  We report the synthesis of a new set of compounds of general structure I (1-20) with structural modifications in the pharmacophoric elements of the previously reported lead UCM-5600. The new derivatives have been evaluated for binding affinity at 5-HT7 and 5-HT1A receptors. The influence of the different structural features in terms of 5-HT7/5-HT1A receptor affinity and selectivity was analyzed by computational simulations of the complexes between compounds I and beta(2)-based 3-D models of these receptors. Compound 18 (HYD1 = 1,3-dihydro-2H-indol-2-one; spacer = -(CH2)(4)-; HYD2 + HYD3 = 3,4-dihydroisoquinolin-2(1H)-yl) exhibits high 5-HT7R affinity (K-i = 7 nM) and selectivity over the 5-HT1AR (31-fold), and has been characterized as a partial agonist of the human 5-HT7R.

  DOI：

  10.1021/jm8014553
• 作为产物：
  描述：

  2-[4-(4-phenylpiperazin-1-yl)butyl]-1H-isoindole-1,3(2H)-dione 在 溶剂黄146 、 锌 作用下， 反应 1.0h， 以44%的产率得到2-[4-(4-phenylpiperazin-1-yl)butyl]isoindolin-1-one
  参考文献：
  名称：

  1-酰亚胺/酰胺基取代的4-（4-芳基哌嗪-1-基）环己烷衍生物的结构-本征活性关系研究；具有抗焦虑活性的新型有效5-HT1A受体药物。

  摘要：

  在柔性长链芳基哌嗪的结构中引入1,4-二取代的环己烷环导致线性约束的有效5-羟色胺（5-HT）（1A）配体。为了追踪该组中的结构-本征活性关系，合成了具有不同环酰亚胺/酰胺末端的一系列新的1-取代的4-（4-芳基哌嗪-1-基）环己烷衍生物，以及它们的柔性四亚甲基类似物，并药理学评估的5-HT（1A）受体。体外结合实验表明，所有化合物均为有效的5-HT（1A）受体试剂（K（i）= 1.9-74 nM）。另外测试的某些衍生物还显示出对α（1）-肾上腺素能受体（K（i）= 2.9-101 nM）和5-HT（7）受体的高亲和力。体内功能检查发现，刚性配体的o-OCH（3）基团在芳基部分和对端末端的环状酰亚胺系统表现得像突触后5-HT（1A）受体拮抗剂。另一方面，未取代的，m-Cl或m-CF（3）取代的衍生物以及在末端片段中具有环状酰胺基的衍生物表现出激动或部分激动活性。测试的四种衍生物中的三种，即

  DOI：

  10.1016/j.bmc.2005.09.060

文献信息

• Synthesis of novel lactam derivatives and their evaluation as ligands for the dopamine receptors, leading to a D4-selective ligand
  作者：Fadi M. Awadallah、Franziska Müller、Jochen Lehmann、Ashraf H. Abadi

  DOI：10.1016/j.bmc.2007.06.002

  日期：2007.9.1

  The preparation of some lactam (cyclic amide) derivatives bearing various phenylpiperazinylbutyl side chains attached to the amide nitrogen together with their dopamine receptor affinity study is described. The synthesis of the target compounds involved the preparation of the intermediate bromobutyl derivatives of the appropriate lactam followed by N-alkylation of the appropriate phenylpiperazines with these intermediates. Radioligand binding studies at D-2-D5 receptor subtypes and a functional calcium assay of the target compounds at D-2 and D-5 receptor subtypes were performed. All compounds, except 12a and 12b, showed selectivity towards the D-2-like receptor subtypes. Selectivity of the indolinone derivatives 11 a-d at the D-4 receptors was observed. Compound 11b exhibited a remarkable affinity to hD(4) receptors with K-i value of 0.04 +/- 0.02 nm and was > 43,000-fold selective over the hD(2) receptor. In the functional assay, all the active compounds were of antagonistic activity. (c) 2007 Elsevier Ltd. All rights reserved.
• Synthesis of New Serotonin 5-HT₇ Receptor Ligands. Determinants of 5-HT₇/5-HT_1A Receptor Selectivity
  作者：Rocío A. Medina、Jessica Sallander、Bellinda Benhamú、Esther Porras、Mercedes Campillo、Leonardo Pardo、María L. López-Rodríguez

  DOI：10.1021/jm8014553

  日期：2009.4.23

  We report the synthesis of a new set of compounds of general structure I (1-20) with structural modifications in the pharmacophoric elements of the previously reported lead UCM-5600. The new derivatives have been evaluated for binding affinity at 5-HT7 and 5-HT1A receptors. The influence of the different structural features in terms of 5-HT7/5-HT1A receptor affinity and selectivity was analyzed by computational simulations of the complexes between compounds I and beta(2)-based 3-D models of these receptors. Compound 18 (HYD1 = 1,3-dihydro-2H-indol-2-one; spacer = -(CH2)(4)-; HYD2 + HYD3 = 3,4-dihydroisoquinolin-2(1H)-yl) exhibits high 5-HT7R affinity (K-i = 7 nM) and selectivity over the 5-HT1AR (31-fold), and has been characterized as a partial agonist of the human 5-HT7R.
• Structure–intrinsic activity relationship studies in the group of 1-imido/amido substituted 4-(4-arylpiperazin-1-yl)cyclohexane derivatives; new, potent 5-HT1A receptor agents with anxiolytic- like activity
  作者：Andrzej J. Bojarski、Maria H. Paluchowska、Beata Duszyńska、Ryszard Bugno、Aleksandra Kłodzińska、Ewa Tatarczyńska、Ewa Chojnacka-Wójcik

  DOI：10.1016/j.bmc.2005.09.060

  日期：2006.3

  1,4-disubstituted cyclohexane ring in the structure of flexible long chain arylpiperazines resulted in linearly constrained, potent serotonin (5-HT)(1A) ligands. In order to trace structure-intrinsic activity relationships in this group, a new series of 1-substituted 4-(4-arylpiperazin-1-yl)cyclohexane derivatives with different cyclic imide/amide termini, and their flexible, tetramethylene analogues

  在柔性长链芳基哌嗪的结构中引入1,4-二取代的环己烷环导致线性约束的有效5-羟色胺（5-HT）（1A）配体。为了追踪该组中的结构-本征活性关系，合成了具有不同环酰亚胺/酰胺末端的一系列新的1-取代的4-（4-芳基哌嗪-1-基）环己烷衍生物，以及它们的柔性四亚甲基类似物，并药理学评估的5-HT（1A）受体。体外结合实验表明，所有化合物均为有效的5-HT（1A）受体试剂（K（i）= 1.9-74 nM）。另外测试的某些衍生物还显示出对α（1）-肾上腺素能受体（K（i）= 2.9-101 nM）和5-HT（7）受体的高亲和力。体内功能检查发现，刚性配体的o-OCH（3）基团在芳基部分和对端末端的环状酰亚胺系统表现得像突触后5-HT（1A）受体拮抗剂。另一方面，未取代的，m-Cl或m-CF（3）取代的衍生物以及在末端片段中具有环状酰胺基的衍生物表现出激动或部分激动活性。测试的四种衍生物中的三种，即