2-(4-bromobutyl)-1-isoindolinone | 155288-43-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异吲哚及其衍生物
• 英文名称: 2-(4-bromobutyl)-1-isoindolinone
• 英文别名: 2-(4-bromobutyl)isoindol-1-one；2-(4-bromobutyl)isoindolin-1-one；2-(4-bromobutyl)-3H-isoindol-1-one
• CAS: 155288-43-0
• 化学式: C₁₂H₁₄BrNO
• 分子量: 268.153
• InChiKey: MNDMMDYVFMDCDF-UHFFFAOYSA-N

物化性质

• 沸点：
  399.5±42.0 °C(Predicted)
• 密度：
  1.412±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  15
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  20.3
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  1-(4-氯苯基)哌嗪 、 2-(4-bromobutyl)-1-isoindolinone 在 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以42%的产率得到2-(4-(4-(4-Chlorophenyl)-1-piperazinyl)butyl)-1-isoindolinone
  参考文献：
  名称：

  Synthesis of novel lactam derivatives and their evaluation as ligands for the dopamine receptors, leading to a D4-selective ligand

  摘要：

  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.

  DOI：

  10.1016/j.bmc.2007.06.002
• 作为产物：
  描述：

  N-(4-溴丁基)邻苯二甲酰亚胺 在 四丁基氟化铵 、 三异丙基硅烷 、 三氟乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 24.25h， 生成 2-(4-bromobutyl)-1-isoindolinone
  参考文献：
  名称：

  靶向胆碱酯酶和 β-淀粉样蛋白的多配体：异二聚体化合物与苄胺药效团的合成、生物学评价

  摘要：

  阿尔茨海默病 (AD) 是一种致命且复杂的神经退行性疾病，有效治疗仍然是未解决的挑战。以多奈哌齐为起点，我们旨在开发具有多向生物学特征的新型潜在抗 AD 药物。我们将目标化合物设计为双结合位点乙酰胆碱酯酶抑制剂，其中 N-苄胺药效团负责与酶的催化阴离子位点相互作用。修饰负责与外围阴离子位点相互作用的杂芳族片段，并引入了三种不同的杂环：异吲哚啉、异吲哚啉-1-one 和糖精。根据药理评价结果，我们确定具有糖精部分的化合物 8b 是最有效和选择性的人乙酰胆碱酯酶抑制剂 (IC50 = 33 nM) 和 β 淀粉样蛋白聚集抑制剂。它作为一种非竞争性乙酰胆碱酯酶抑制剂，能够在体外穿过血脑屏障。我们相信化合物 8b 是一种重要的先导化合物，可作为潜在的抗 AD 药物进一步开发。

  DOI：

  10.1002/ardp.201500117

文献信息

• Cyclic Benzamides as Mixed Dopamine D2/Serotonin 5-HT2 Receptor Antagonists: Potential Atypical Antipsychotic Agents
  作者：Mark H. Norman、Greg C. Rigdon、Frank Navas、Barrett R. Cooper

  DOI：10.1021/jm00042a008

  日期：1994.8

  A series of novel 4-(4-(1,2-benzisothiazol-3-yl)-1-piperazinyl)butyl) cyclic amides was prepared and evaluated as potential antipsychotic agents. The target compounds were examined in vitro for their binding affinities to the dopamine D2, serotonin 5-HT2, and serotonin 5-HT1a receptors and in vivo for their ability to antagonize the apomorphine-induced climbing response in mice. Derivatives that exhibited

  制备了一系列新颖的4-（4-（1,2-苯并噻唑-3-基）-1-哌嗪基）丁基）环酰胺，并将其评估为潜在的抗精神病药。在体外检查靶标化合物与多巴胺D2、5-羟色胺5-HT2和5-羟色胺5-HT1a受体的结合亲和力，并在体内拮抗阿朴吗啡诱导的小鼠爬升反应的能力。选择在体外表现出良好的D2 / 5-HT2选择性和在体内具有良好效能的衍生物，以在旨在评估其潜在锥体外系副作用的测试中进行进一步评估。本文讨论的结构修饰着眼于双环酰胺亚基，导致制备各种杂环系统（即邻苯二甲酰亚胺，异吲哚啉酮，异喹啉酮，苯并ze庚酮，吲唑酮，酞嗪酮，4-甲基酞嗪酮，1,1-二甲基苯并异噻唑酮，苯并三嗪酮，高邻苯二甲酰亚胺，苯并异噻唑酮，邻苯二嗪二酮，喹唑啉和饱和邻苯二氮酮。发现该系列中的效力和选择性取决于环的大小，共价连接单元的性质，官能团的相对位置，不饱和度和相对立体化学。通常，在这项研究中检查的环状苯甲酰胺表现出受体结合
• 噻吩并环化合物及其制备方法和应用
  申请人：中国科学院分子细胞科学卓越创新中心

  公开号：CN115772175A

  公开（公告）日：2023-03-10

  本发明公开了一种噻吩并环化合物及其制备方法和应用。本发明的噻吩并环化合物的结构如式I所示。本发明的化合物对多巴胺受体和5‑羟色胺受体中的至少一种具有良好的亲和力和激动活性。
• 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.
• N-Substituted-3-arylpyrrolidines: Potent and selective ligands at serotonin 1A receptor
  作者：Kyo Han Ahn、Seok Jong Lee、Chang-Ho Lee、Chang Y. Hong、Tae Kyo Park

  DOI：10.1016/s0960-894x(99)00201-2

  日期：1999.5

  3-Arylpyrrolidines are synthesized through the coupling of N-benzyl-3-(methanesulfonyloxy)pyrrolidine with diarylcuprates. Pharmacological evaluation of a series of N-substituted-3-arylpyrrolidines toward several neurotransmitter receptors indicated that some of them are good ligands for serotonin 1A receptor. Particularly, N-[(N-saccharino)butyl]pyrrolidines were found to be potent and selective ligands. A preliminary biological evaluation for several selected compounds indicated that they are potentially effective antianxiety and antidepressant agents. (C) 1999 Elsevier Science Ltd. All rights reserved.
• Effect of Linking Bridge Modifications on the Antipsychotic Profile of Some Phthalimide and Isoindolinone Derivatives
  作者：Mark H. Norman、Douglas J. Minick、Greg C. Rigdon

  DOI：10.1021/jm9502201

  日期：1996.1.1

  A series of phthalimide and isoindolinone derivatives bridged to 4-(1,2-benzisothiazo1-3-yl)-1-piperazinyl was prepared. The compounds were evaluated in vitro at dopamine D-2 and serotonin 5-HT1a and 5-HT2 receptors and in vivo for their ability to antagonize the apomorphine-induced climbing response in mice. The effects of bridge length and conformation on the biological activity of these potential antipsychotic agents are discussed. A four-carbon spacer provided optimal activity within the two homologous series. Conformational investigations of the lead compound, isoindolinone 2, were conducted in an attempt to account for the superior activity observed for the butyl derivatives. On the basis of NMR and molecular modeling studies, two types of folded structures were proposed and several conformationally restrained analogues were synthesized. In general, restrictions incorporated within the linking bridge were detrimental to activity.