3-(2-(1-哌嗪)乙基)-1H-吲哚 | 4644-97-7

• 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
• 中文名称: 3-(2-(1-哌嗪)乙基)-1H-吲哚
• 英文名称: 3-(2-(piperazin-1-yl)ethyl)-1H-indole
• 英文别名: 3-(2-piperazin-1-ylethyl)-1H-indole
• CAS: 4644-97-7
• 化学式: C₁₄H₁₉N₃
• 分子量: 229.325
• InChiKey: ZAJWVEMEALEQMZ-UHFFFAOYSA-N

物化性质

• 沸点：
  415.4±30.0 °C(Predicted)
• 密度：
  1.122±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  31.1
• 氢给体数：
  2
• 氢受体数：
  2

安全信息

• 海关编码：
  2933990090

反应信息

• 作为反应物：
  描述：

  4-chloro-5,6-tetramethylene-7-cyanopyrrolo<3,2-d>pyrimidin-4-one 、 3-(2-(1-哌嗪)乙基)-1H-吲哚 在 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 生成 4-(4-(2-(1H-indol-3-yl)ethyl)piperazin-1-yl)-6,7,8,9-tetrahydropyrimido[4,5-b]indolizine-10-carbonitrile
  参考文献：
  名称：

  Studies on Pyrrolopyrimidines as Selective Inhibitors of Multidrug-Resistance- Associated Protein in Multidrug Resistance

  摘要：

  Multidrug resistance mediated by P-glycoprotein (Pgp) or multidrug-resistance-associated protein (MRP) remains a major obstacle for successful treatment of cancer. Inhibition of Pgp and MRP transport is important for high efficacy of anticancer drugs. While several Pgp inhibitors have entered clinical trials, the development of specific MRP1 inhibitors is still in its infancy. In our screening program, we have identified a pyrrolopyrimidine (4) as a novel and selective MRP1 inhibitor. Subsequent SAR work on the 4-position of the template revealed the phenethylpiperazine side chain as a potent replacement of the benzylthio group of the lead molecule. Introduction of groups at the 2-position seems to have no detrimental effect on activity. Modifications to the nitrile group at the 7-position resulted in the identification of analogues with groups, such as amides, with superior pharmacokinetic profiles. In vivo efficacy has been demonstrated by xenograft studies on selected compounds.

  DOI：

  10.1021/jm031011g
• 作为产物：
  描述：

  1-(1H-indol-3-yl)-2-(piperazin-1-yl)ethanone 在 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 为溶剂， 以80 %的产率得到3-(2-(1-哌嗪)乙基)-1H-吲哚
  参考文献：
  名称：

  部分杂环稠合吲哚衍生物作为潜在抗氧化剂的合成及仿药性评价

  摘要：

  背景：吲哚及其衍生物具有广泛的药理作用，包括镇痛、抗菌、抗抑郁、抗糖尿病、抗惊厥、抗蠕虫和抗炎等特性。它们是当今许多强大的抗氧化药物的关键结构成分。目的：使用 Schotten-Baumann 反应，将吲哚环与其他关键杂环部分（如吗啉、咪唑、哌啶和哌嗪）在活性 3 位连接，然后测试其抗氧化活性。方法：衍生物的合成在适当的条件下完成，并通过红外、核磁共振（1H 和 13C）和质谱进行表征。使用瑞士 ADME 在线应用程序，还确定了 ADME 属性。体外抗氧化活性采用DPPH和还原力法测定。结果：在DPPH测定中，化合物5a(IC50=1.01±0.22μg/mL)、5k(IC50=1.21±0.07μg/mL)，而化合物5a(EC50=23±1.00μg/mL)、5h(EC50= 26±2.42 μg/mL) 在还原力测定中与标准抗坏血酸相比是最有效的。化合物 5a、5h 和 5k 表现出与标准品相当的最大效力。ADME

  DOI：

  10.2174/1386207326666230102111810

文献信息

• Discovery of potent antitubercular agents: Design, synthesis and biological evaluation of 4-(3-(4-substitutedpiperazin-1-yl)-quinoxalin-2-yl)-naphthalen-1-ol analogues
  作者：Adinarayana Nandikolla、Yogesh Mahadu Khetmalis、Kalaga Mahalakshmi Naidu、Banoth Karan Kumar、Sankaranarayanan Murugesan、Kondapalli Venkata Gowri Chandra Sekhar

  DOI：10.1016/j.tiv.2022.105370

  日期：2022.8

  in vitro antitubercular activity against Mycobacterium tuberculosis H37Rv strain. These compounds exhibited minimum inhibitory concentration in the range of 1.56–50 μg/mL. Among these derivatives, compounds 5a, 5b, 5f, 5m, 5p, and 5r displayed moderate activity (MIC 6.25 μg/mL). Compounds 5c, 5d, 5g, 5l, and 5o showed significant antitubercular activity (MIC 3.125 μg/mL), while compounds 5h, 5n, and

  合成、表征和筛选了一系列 25 种新型 4-(3-(4-取代的哌嗪-1-基)-喹喔啉-2-基)-萘-1-醇类似物对结核分枝杆菌的体外抗结核活性H37Rv 菌株。这些化合物在 1.56–50 μg/mL 范围内表现出最小抑制浓度。在这些衍生物中，化合物5a、5b、5f、5m、5p和5r表现出中等活性（MIC 6.25 μg/mL）。化合物5c、5d、5g、5l和5o显示出显着的抗结核活性（MIC 3.125 μg/mL），而化合物5h、5n和5q表现出有效的抗结核活性（MIC 1.56 μg/mL）。此外，对该系列的活性类似物对小鼠巨噬细胞进行MTT测定，以评估新合成化合物的细胞毒作用，并建立化合物的选择性指数。最活跃的化合物（5h、5n和5q）的选择性指数值 > 47，表明这些化合物适合进一步潜在的药物开发。使用莫西沙星作为标准，进行分子对接研究以了解选定的显着活性和弱活性化合物与靶酶分枝杆菌拓扑异构酶
• COMPOUNDS WITH A COMBINATION OF CANNABINOID CB1 ANTAGONISM AND SEROTONIN REUPTAKE INHIBITION
  申请人：Lange Josephus H.M.

  公开号：US20080214559A1

  公开（公告）日：2008-09-04

  Compounds with a combination of cannabinoid CB 1 antagonism and serotonin re-uptake inhibition, pharmaceutical compositions containing these compounds, methods for preparing these compounds, methods for preparing novel intermediates useful for their synthesis, and methods for preparing these compositions are disclosed. Uses of such compounds and compositions, particularly their use in administering them to patients to achieve a therapeutic effect in psychosis, anxiety, depression, attention deficits, cognitive disorders, obesity, drug dependence, Parkinson's disease, Alzheimer's disease, pain disorders, neuropathic pain disorders and sexual disorders are disclosed. In at least one embodiment, the invention relates to compounds of the general formula (1); wherein the substitutents have the definitions given in the specification.

  本发明涉及一种具有大麻素CB1拮抗和血清素再摄取抑制的化合物组合，含有这些化合物的制药组合物，制备这些化合物的方法，制备用于其合成的新型中间体的方法，以及制备这些组合物的方法。本发明还涉及这些化合物和组合物的用途，特别是将它们用于给患者施用，以在精神病、焦虑、抑郁、注意力缺陷、认知障碍、肥胖症、药物依赖、帕金森病、阿尔茨海默病、疼痛障碍、神经痛障碍和性障碍中实现治疗效果。在至少一个实施例中，本发明涉及一般式（1）的化合物；其中取代基具有规范中给出的定义。
• 9-Deazapurines as Broad-Spectrum Inhibitors of the ABC Transport Proteins P-Glycoprotein, Multidrug Resistance-Associated Protein 1, and Breast Cancer Resistance Protein
  作者：Katja Stefan、Sven Marcel Schmitt、Michael Wiese

  DOI：10.1021/acs.jmedchem.7b00788

  日期：2017.11.9

  P-Glycoprotein (P-gp, ABCB1), multidrug resistance-associated protein 1 (MRP1, ABCC1), and breast cancer resistance protein (BCRP, ABCG2) are the three major ABC transport proteins conferring resistance to many structurally diverse anticancer agents, leading to the phenomenon called multidrug resistance (MDR). Much effort has been put into the development of clinically useful compounds to reverse MDR. Broad-spectrum inhibitors of ABC transport proteins can be of great use in cancers that simultaneously coexpress two or three transporters. In this work, we continued our effort to generate new, potent, nontoxic, and multiply effective inhibitors of the three major ABC transporters. The best compound was active in a very low micromolar concentration range against all three transporters and restored sensitivity toward daunorubicin (P-gp and MRP1) and SN-38 (BCRP) in A2780/ADR (P-gp), H69AR (MRP1), and MDCK II BCRP (BCRP) cells. Additionally, the compound is a noncompetitive inhibitor of daunorubicin (MRP1), calcein AM (P-gp), and pheophorbide A (BCRP) transport.
• US8138174B2
  申请人：——

  公开号：US8138174B2

  公开（公告）日：2012-03-20
• [EN] COMPOUNDS WITH A COMBINATION OF CANNABINOID-CB1 ANTAGONISM AND SEROTONIN REUPTAKE INHIBITION<br/>[FR] COMPOSÉS ANTAGONISTES DES CANNABINOÏDES CB1 ET INHIBITEURS DE LA RÉABSORPTION DE LA SÉROTONINE
  申请人：SOLVAY PHARM BV

  公开号：WO2008084057A1

  公开（公告）日：2008-07-17

  [EN] This invention relates to compounds with a combination of cannabinoid-CB₁antagonism and serotonin reuptake inhibition to pharmaceutical compositions containing these compounds, to methods for preparing the compounds, methods for preparing novel intermediates useful for their synthesis, and methods for preparing compositions. The invention also relates to the uses of such compounds and compositions, particularly their use in administering them to patients to achieve a therapeutic effect in psychosis, anxiety, depression, attention deficits, cognitive disorders, obesity, drug dependence, Parkinson's disease, Alzheimer's disease, pain disorders, neuropathic pain disorders and sexual disorders. In particular the invention relates to compoundsof the general formula (I): wherein the symbols have the meanings given in the specification.
  [FR] L'invention concerne des composés antagonistes des cannabinoïdes CB1 et inhibiteurs de la réabsorption de la sérotonine, des compositions pharmaceutiques contenant lesdits composés, des procédés de préparation des composés, des procédés de préparation de nouveaux intermédiaires utilisés pour leur synthèse et des procédés de préparation des compositions. L'invention concerne également les utilisations desdits composés et compositions, en particulier leur utilisation pour les administrer à des patients en vue d'obtenir un effet thérapeutique sur la psychose, l'anxiété, la dépression, les troubles déficitaires de l'attention, les troubles cognitifs, l'obésité, la toxicomanie, la maladie de Parkinson, la maladie d'Alzheimer, les troubles liés à la douleur, les troubles liés aux douleurs neuropathiques et les troubles sexuels. L'invention concerne, en particulier, des composés représentés par la formule générale (1) dans laquelle les symboles sont tels que décrits dans les spécifications.