1-(4-bromobutyl)-1,3-dihydro-2H-indol-2-one | 162400-63-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 1-(4-bromobutyl)-1,3-dihydro-2H-indol-2-one
• 英文别名: 1-(4-bromobutyl)indolin-2-one；1-(4-bromobutyl)-3H-indol-2-one
• CAS: 162400-63-7
• 化学式: C₁₂H₁₄BrNO
• 分子量: 268.153
• InChiKey: WLUBVNFQKVTTQY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 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-bromobutyl)-1,3-dihydro-2H-indol-2-one 在 硫酸 、 sodium cyanoborohydride 、 溶剂黄146 、 三乙胺 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 12.0h， 生成
  参考文献：
  名称：

  10.1691/ph.2015.5549

  摘要：

  DOI：

  10.1691/ph.2015.5549
• 作为产物：
  描述：

  1,4-二溴丁烷 、 2-吲哚酮 在 potassium carbonate 作用下， 以 乙腈 为溶剂， 反应 20.0h， 生成 1-(4-bromobutyl)-1,3-dihydro-2H-indol-2-one
  参考文献：
  名称：

  A Search for New 5-HT1A/5-HT2A Receptor Ligands. In Vitro and in vivo Studies of 1-[ω-(4-Aryl-1-piperazinyl)alkyl]indolin-2(1H)-ones

  摘要：

  A series of 1-{omega-(4-aryl-1-piperazinyl)alkyl]indolin-2(1H)-one derivatives 2-14 was synthesized in order to obtain ligands with a dual 5-HT1A/5-HT2A activity. The majority of those compounds (2-5, 7, 10-13) exhibited a high 5-HT1A (K-i = 2 - 44 nM) and/or 5-HT2A affinity (K-i = 51 and 39 for 5 and 7, respectively). Induction of lower lip retraction (LLR) and behavioral syndrome and inhibition of these efects evoked by 8-hydroxy-2-(di-n-propyl-amino)tetralin (8-OH-DPAT) were used for determination the agonistic and antagonistic activity, respectively, at 5-HT1A receptors. The 5-HT2A antagonistic activity was assessed by the blocking effect on the head twitches induced by (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) in mice. Two of the tested compounds, 1-{3-[4-(3-chlorophenyl)-1-piperazinyl]propyl}-6-fluoroindolin-2(1H)-one (5) and 1-{3-[4-(2-methoxyphenyl)-1 piperazinyl]propyl}indolin-2(1H)-one (7), demonstrated a high 5-HT1A/5-HT2A affinity and an in vivo antagonistic activity towards both receptor subtypes.

  DOI：

  10.1002/(sici)1521-4184(199810)331:10<325::aid-ardp325>3.0.co;2-6

文献信息

• 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.
• A Search for New 5-HT1A/5-HT2A Receptor Ligands. In Vitro and in vivo Studies of 1-[ω-(4-Aryl-1-piperazinyl)alkyl]indolin-2(1H)-ones
  作者：Maria J. Mokrosz、Beata Duszyńska、Stanisław Misztal、Aleksandra Kłodzińska、Ewa Tatarczyńska、Ewa Chojnacka-Wójcik、Marta Dziedzicka-Wasylewska

  DOI：10.1002/(sici)1521-4184(199810)331:10<325::aid-ardp325>3.0.co;2-6

  日期：1998.10

  A series of 1-omega-(4-aryl-1-piperazinyl)alkyl]indolin-2(1H)-one derivatives 2-14 was synthesized in order to obtain ligands with a dual 5-HT1A/5-HT2A activity. The majority of those compounds (2-5, 7, 10-13) exhibited a high 5-HT1A (K-i = 2 - 44 nM) and/or 5-HT2A affinity (K-i = 51 and 39 for 5 and 7, respectively). Induction of lower lip retraction (LLR) and behavioral syndrome and inhibition of these efects evoked by 8-hydroxy-2-(di-n-propyl-amino)tetralin (8-OH-DPAT) were used for determination the agonistic and antagonistic activity, respectively, at 5-HT1A receptors. The 5-HT2A antagonistic activity was assessed by the blocking effect on the head twitches induced by (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) in mice. Two of the tested compounds, 1-3-[4-(3-chlorophenyl)-1-piperazinyl]propyl}-6-fluoroindolin-2(1H)-one (5) and 1-3-[4-(2-methoxyphenyl)-1 piperazinyl]propyl}indolin-2(1H)-one (7), demonstrated a high 5-HT1A/5-HT2A affinity and an in vivo antagonistic activity towards both receptor subtypes.
• 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.
• The Extracellular Entrance Provides Selectivity to Serotonin 5-HT₇ Receptor Antagonists with Antidepressant-like Behavior in Vivo
  作者：Rocío A. Medina、Henar Vázquez-Villa、José C. Gómez-Tamayo、Bellinda Benhamú、Mar Martín-Fontecha、Tania de la Fuente、Gianluigi Caltabiano、Peter B. Hedlund、Leonardo Pardo、María L. López-Rodríguez

  DOI：10.1021/jm500880c

  日期：2014.8.14

  The finding that ergotamine binds serotonin receptors in a less conserved extended binding pocket close to the extracellular entrance, in addition to the orthosteric site, allowed us to obtain 5-HT7R antagonist 6 endowed with high affinity (Ki=0.7 nM) and significant 5-HT1AR selectivity (ratio>1428). Compound 6 exhibits in vivo antidepressant-like effect (1 mg/kg, ip) mediated by the 5-HT7R, which reveals its interest as a putative research tool or pharmaceutical in depression disorders.
• 10.1691/ph.2015.5549
  作者：Li, Gu-Cai、Zhang, Bian-Ling、Xia, Jiao-Yun、Fang, Zheng-Jun

  DOI：10.1691/ph.2015.5549

  日期：——