N-(4-bromobutyl)-1H-indole-2-carboxamide | 600709-90-8

• 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: N-(4-bromobutyl)-1H-indole-2-carboxamide
• 英文别名: N-[1-(4-bromo)butyl]indole-2-carboxamide；N2-(4-bromobutyl)-1H-2-indolecarboxamide
• CAS: 600709-90-8
• 化学式: C₁₃H₁₅BrN₂O
• 分子量: 295.179
• InChiKey: ZJPDFDKMGJBION-UHFFFAOYSA-N

物化性质

• 熔点：
  133-134 °C(Solv: ethyl acetate (141-78-6))
• 沸点：
  538.6±30.0 °C(Predicted)
• 密度：
  1.440±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  17
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  44.9
• 氢给体数：
  2
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  (R)-5-(甲基氨基)-5,6-二氢-1H-咪唑并[4,5,1-ij]喹啉-2(4h)-酮 、 N-(4-bromobutyl)-1H-indole-2-carboxamide 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 以20%的产率得到(R)-N-(4-(methyl(2-oxo-2,4,5,6-tetrahydro-1H-imidazo[4,5,1-ij]-quinolin-5-yl)amino)butyl)-1H-indole-2-carboxamide
  参考文献：
  名称：

  （R）-5-（甲氨基）-5,6-二氢-4 H-咪唑并[4,5,1- ij ]喹啉-2（1 H）-one（舒马尼罗）的新类似物为多巴胺D 2提供了线索/ D 3受体激动剂选择性

  摘要：

  sumanirole的新的1-，5-，和8-取代的类似物（1），多巴胺d 2 / d 3受体（d 2 R / d 3 R）激动剂，合成。当与激动剂放射性配体[ 3 H] 7-羟基-N，N-二丙基-2-氨基四氢萘（7-OH-DPAT）竞争测定时，在D 2 R和D 3 R处的结合亲和力都较高。[ 3 H] N-甲基哌啶。尽管1被确认为D 2R-优先激动剂，它在结合和功能研究中的选择性比以前报道的要低。在G o BRET和有丝分裂发生功能测定中，所有类似物均被确定为D 2 R / D 3 R激动剂。在D 3 R处检测到N -1-取代的类似物的功效下降。相比之下，N -5-烷基取代的类似物，尤其是正丁基芳基酰胺（22b和22c），均显示出改善的亲和力。 D 2 R超过1既不损失功效也不增加选择性。计算建模为D提供了结构基础2的1R选择性1，示出了如何在高度同源的正构结合位点的细微差别（OBS）中差异影响d

  DOI：

  10.1021/acs.jmedchem.5b01612
• 作为产物：
  描述：

  吲哚-2-羧酸 在 四溴化碳 、 1-羟基苯并三唑一水物 、 N,N'-二环己基碳二亚胺 、 三苯基膦 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 生成 N-(4-bromobutyl)-1H-indole-2-carboxamide
  参考文献：
  名称：

  有效和高度选择性的D3受体配体的合成和药理评估：抑制可卡因的寻找行为和多巴胺D3 / D2受体的作用。

  摘要：

  描述了一系列与BP897（3）结构相关的新型芳烷基哌嗪的合成，药理学评估和构效关系（SAR）。在结合研究中，针对一组多巴胺，5-羟色胺和去甲肾上腺素受体亚型对新衍生物进行了测试。SAR研究主要集中于多巴胺D（3）受体，揭示了高受体亲和力和选择性所需的许多结构特征。探索了几种杂芳族系统的多巴胺受体亲和力，并结合了合成，生物学和分子模型，用于鉴定有效和选择性D（3）受体配体发展的新型结构。引入与二氯苯基哌嗪系统连接的吲哚环提供了迄今为止已知的两种最有效和选择性的配体（D（3）受体亲和力在皮摩尔范围内）。强大的D（3）受体配体的子集的内在药理学性质也通过[（35）S] -GTPgammaS结合测定进行了评估。动物研究的证据尤其突出了多巴胺能系统在环境刺激如何诱导药物寻求行为中的作用。因此，我们测试了两种新型D（3）受体部分激动剂和一种有效的D（3）选择性拮抗剂，在体内在长期禁欲后通过重新引入可卡

  DOI：

  10.1021/jm0211220

文献信息

• Novel Aryl Piperazine Derivatives With Medical Utility
  申请人：Campiani Giuseppe

  公开号：US20090238761A1

  公开（公告）日：2009-09-24

  This invention provides novel aryl piperazine derivatives having medical utility, in particular as modulators of dopamine and serotonin receptors, preferably the D 3 , D 2 -like and 5-HT 2 receptor subtypes, and in particular useful for the treatment of neuropsychiatric disorders incl. schizophrenia.

  这项发明提供了具有医疗效用的新型芳基哌嗪衍生物，特别是作为多巴胺和5-羟色胺受体的调节剂，优选为D3、D2样和5-HT2受体亚型，特别适用于治疗包括精神分裂症在内的神经精神障碍。
• Novel pyrrolo[2,1-c][1,4] benzodiazepine-indole derivatives, their preparation process, and uses of the same
  申请人：Kaohsiung Medical University

  公开号：US20040054168A1

  公开（公告）日：2004-03-18

  Disclosed herein are novel pyrrolo[2,1-c][1,4]benzodiazepine-indole derivatives of formula (I): 1 wherein each of the substituents is given the definition as set forth in the Specification and claims. Also disclosed are the preparation process of these derivatives and their uses in the manufacture of pharmaceutical compositions.

  本文披露了一种新颖的嘧啶并[2,1-c][1,4]苯二氮杂环己烯-吲哚衍生物，化学式（I）如下：其中每个取代基的定义如规范和索赔中所述。还披露了这些衍生物的制备过程以及它们在制造药物组合物中的用途。
• Novel Bivalent Ligands Based on the Sumanirole Pharmacophore Reveal Dopamine D₂ Receptor (D₂R) Biased Agonism
  作者：Alessandro Bonifazi、Hideaki Yano、Michael P. Ellenberger、Ludovic Muller、Vivek Kumar、Mu-Fa Zou、Ning Sheng Cai、Adrian M. Guerrero、Amina S. Woods、Lei Shi、Amy Hauck Newman

  DOI：10.1021/acs.jmedchem.6b01875

  日期：2017.4.13

  The development of bivalent ligands has attracted interest as a way to potentially improve the selectivity and/or affinity for a specific receptor subtype. The ability to bind two distinct receptor binding sites simultaneously can allow the selective activation of specific G-protein dependent or beta-arrestin-mediated cascade pathways. Herein, we developed an extended SAR study using sumanirole (1) as the primary pharmacophore. We found that substitutions in the N-1- and/or N-S-positions, physiochemical properties of those substituents, and secondary aromatic pharmacophores can enhance agonist efficacy for the cAMP inhibition mediated by G(i/o)-proteins, while reducing or suppressing potency and efficacy toward beta-arrestin recruitment. Compound 19 was identified as a new lead for its selective D-2 G-protein biased agonism with an EC50 in the subnanomolar range. Structure activity correlations were observed between substitutions in positions N-1 and/or N-5 of 1 and the capacity of the new bivalent compounds to selectively activate G-proteins versus beta-arrestin recruitment in D2R-BRET functional assays.
• Targeting Dopamine D₃ and Serotonin 5-HT_1A and 5-HT_2A Receptors for Developing Effective Antipsychotics: Synthesis, Biological Characterization, and Behavioral Studies
  作者：Margherita Brindisi、Stefania Butini、Silvia Franceschini、Simone Brogi、Francesco Trotta、Sindu Ros、Alfredo Cagnotto、Mario Salmona、Alice Casagni、Marco Andreassi、Simona Saponara、Beatrice Gorelli、Pia Weikop、Jens D. Mikkelsen、Jorgen Scheel-Kruger、Karin Sandager-Nielsen、Ettore Novellino、Giuseppe Campiani、Sandra Gemma

  DOI：10.1021/jm501119j

  日期：2014.11.26

  Combination of dopamine D-3 antagonism, serotonin 5-HT1A partial agonism, and antagonism at 5-HT2A leads to a novel approach to potent atypical antipsychotics. Exploitation of the original structureactivity relationships resulted in the identification of safe and effective antipsychotics devoid of extrapyramidal symptoms liability, sedation, and catalepsy. The potential atypical antipsychotic 5bb was selected for further pharmacological investigation. The distribution of c-fos positive cells in the ventral striatum confirmed the atypical antipsychotic profile of 5bb in agreement with behavioral rodent studies. 5bb administered orally demonstrated a biphasic effect on the MK801-induced hyperactivity at dose levels not able to induce sedation, catalepsy, or learning impairment in passive avoidance. In microdialysis studies, 5bb increased the dopamine efflux in the medial prefrontal cortex. Thus, 5bb represents a valuable lead for the development of atypical antipsychotics endowed with a unique pharmacological profile for addressing negative symptoms and cognitive deficits in schizophrenia.
• Design, Synthesis, and Biological Evaluation of Pyrrolo[2,1-<i>c</i>][1,4]benzodiazepine and Indole Conjugates as Anticancer Agents
  作者：Jeh-Jeng Wang、Yu-Kai Shen、Wan-Ping Hu、Ming-Chu Hsieh、Fu-Lung Lin、Ming-Kuan Hsu、Mei-Hui Hsu

  DOI：10.1021/jm050956q

  日期：2006.2.1

  A series of novel pyrrolo[2,1-c][1,4]benzodiazepine (PBD) hybrids linked with indole carboxylates is described. These compounds were prepared by linking C-8 of 3 (DC-81) with an indole 2-carbonyl moiety (9) through carbon chain linkers to afford PBD hybrid agents 17-21 in good yields. Preliminary in vivo tests show that these hybrid agents have potent antitumor activity. The cytotoxic studies of the hybrid agents on human melanoma A2058 cells indicate most of the hybrids induced higher cytotoxicity, better DNA-binding ability, an increase in the apoptotic sub-G1 population, and a significant reduction in Delta Psi(mt) relative to compound 3. In addition, DNA flow cytometric analysis shows that hybrids actively induce a marked loss of cells from the G2/M phase of the cell cycle, which progresses to early apoptosis as detected by flow cytometry after double-staining with annexin V and propidium iodide (PI). Thus, we suggest that the hybrid agents are potent inducers of cell apoptosis in A2058 cells.