1-methyl-1H-pyrrolo[3,2-b]pyridine-3-carbaldehyde | 860297-51-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯并吡啶类
• 英文名称: 1-methyl-1H-pyrrolo[3,2-b]pyridine-3-carbaldehyde
• 英文别名: 1-Methyl-1H-pyrrolo[3,2-b]pyridine-3-carbaldehyde；1-methylpyrrolo[3,2-b]pyridine-3-carbaldehyde
• CAS: 860297-51-4
• 化学式: C₉H₈N₂O
• 分子量: 160.175
• InChiKey: YFVZIDWCXCIAEC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 重原子数：
  12
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  34.9
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1-methyl-1H-pyrrolo[3,2-b]pyridine-3-carbaldehyde 在 palladium diacetate 、 四氯化钛 、 potassium carbonate 、 三乙胺 、 三苯基膦 、 calcium chloride 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 反应 0.42h， 生成 N-(2-(dimethylamino)ethyl)-11-methyl-11H-pyrido[2',3':4,5] pyrrolo[2,3-f]quinoline-5-carboxamide
  参考文献：
  名称：

  Design and synthesis of pyrido[3,2-α]carbazole derivatives and their analogues as potent antitumour agents

  摘要：

  A series of pyrido[3,2-a]carbazole derivatives and their analogues have been prepared and evaluated for their antitumour activity against human lung cancer A549 cells and colon cancer HT29 cells. The intermediates 4a-4k are successfully synthesized from 1a-1k and ethyl 2-(3-bromopyridin-2-yl)acetate by Knoevenagel condensation and intramolecular Heck-type reaction, and this is a novel and efficient synthetic approach to the core scaffold of the target compounds. These target compounds have shown an interesting antitumour profile towards the tested cell lines with IC50 values ranging from 0.07 mu M to 4.45 mu M. Among all the compounds synthesized, 8 compounds show higher potency than R16, 12 compounds are as potent as R16, and 6 compounds are less potent than R16. The best compound 24 is 7 times and approximately 10 times as potent as R16 against A549 and HT29 cells, respectively. (c) 2013 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2013.05.045
• 作为产物：
  描述：

  1-甲基-1H-吡咯并[3,2-b]吡啶 、 乌洛托品 在 三氟乙酸 作用下， 生成 1-methyl-1H-pyrrolo[3,2-b]pyridine-3-carbaldehyde
  参考文献：
  名称：

  Discovery of cyclopentane- and cyclohexane-trans-1,3-diamines as potent melanin-concentrating hormone receptor 1 antagonists

  摘要：

  We herein report the optimization of cyclopentane- and cyclohexane-1,3-diamine derivatives as novel and potent MCH-R I antagonists. Structural modifications of the 2-amino-quinoline and thiophene moieties found in the initial lead compound served to improve its metabolic stability profile and MCH-RI affinity, and revealed unprecedented SAR when compared to other 2-aminoquinoline-containing NICH-R1 antagonists. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.05.034

文献信息

• [EN] THERAPEUTIC AGENTS I<br/>[FR] AGENTS THERAPEUTIQUES I
  申请人：ASTRAZENECA AB

  公开号：WO2005066132A1

  公开（公告）日：2005-07-21

  Compounds of formula(I), processes for preparing such compounds, their use in the treatment of obesity, psychiatric disorders, cognitive disorders, memory disorders, schizophrenia, epilepsy, and related conditions, and neurological disorders such as dementia, multiple sclerosis, Parkinson's disease, Huntington's chorea and Alzheimer's disease and pain related disorders, and pharmaceutical compositions containing them.

  化合物的化学式(I)，制备这种化合物的方法，它们在治疗肥胖、精神障碍、认知障碍、记忆障碍、精神分裂症、癫痫以及相关疾病，以及神经系统疾病如痴呆症、多发性硬化症、帕金森病、亨廷顿舞蹈症、阿尔茨海默病和与疼痛相关的疾病中的应用，以及含有它们的药物组合物。
• Discovery of Novel <i>Plasmodium falciparum</i> HDAC1 Inhibitors with Dual-Stage Antimalarial Potency and Improved Safety Based on the Clinical Anticancer Drug Candidate Quisinostat
  作者：Ruoxi Li、Dazheng Ling、Tongke Tang、Zhenghui Huang、Manjiong Wang、Yan Ding、Taiping Liu、Hanwen Wei、Wenyue Xu、Fei Mao、Jin Zhu、Xiaokang Li、Lubin Jiang、Jian Li

  DOI：10.1021/acs.jmedchem.0c02104

  日期：2021.2.25

  clinical anticancer drug candidate quisinostat as a novel and potent antimalarial lead compound. To further enhance the antimalarial effect and improve safety, 31 novel spirocyclic hydroxamic acid derivatives were synthesized based on the structure of quisinostat, and their antimalarial activities and cytotoxicity were evaluated. Among them, compound 11 displayed broad potency in vitro against several

  以前，我们将临床抗癌药物候选药物Quisinostat鉴定为一种新型且有效的抗疟铅化合物。为了进一步增强抗疟作用，提高安全性，在喹诺司他的结构基础上合成了31种新型螺环异羟肟酸衍生物，并对其抗疟活性和细胞毒性进行了评价。其中，化合物11在体外对几种多重耐药的疟疾寄生虫，特别是两种对青蒿素耐药的临床分离株显示出广泛的效价。此外，有11种可以在体内消除肝脏和红细胞寄生虫，杀死所有形态异常的红细胞寄生虫，具有对裂殖子的特效，并显示出可接受的代谢稳定性和药代动力学特性。蛋白质印迹分析，PfHDAC基因敲低和酶抑制实验共同证实Pf HDAC1是11的目标。总之，11是一种结构新颖的Pf HDAC1抑制剂，具有预防和治愈疟疾，克服多重耐药性的潜力，并为抗疟药研究提供了前瞻性的原型。
• Drug Repurposing of Quisinostat to Discover Novel <i>Plasmodium falciparum</i> HDAC1 Inhibitors with Enhanced Triple-Stage Antimalarial Activity and Improved Safety
  作者：Manjiong Wang、Tongke Tang、Ruoxi Li、Zhenghui Huang、Dazheng Ling、Lulu Zheng、Yan Ding、Taiping Liu、Wenyue Xu、Feng Zhu、Hui Min、Rachasak Boonhok、Fei Mao、Jin Zhu、Xiaokang Li、Lubin Jiang、Jian Li

  DOI：10.1021/acs.jmedchem.1c01993

  日期：2022.3.10

  significant in vivo killing effect against all life cycles of parasites, including the blood stage, liver stage, and gametocyte stage, indicating its potential for the simultaneous treatment, chemoprevention, and blockage of malaria transmission. Compared with quisinostat, JX35 exhibited stronger antimalarial efficacy, more adequate safety, and good pharmacokinetic properties. Additionally, mechanistic

  我们之前的工作发现，临床组蛋白去乙酰化酶 (HDAC) 抑制剂 quisinostat 表现出显着的抗疟作用，但具有严重的毒性。本工作以quisinostat为先导化合物设计合成了35种新型衍生物，并对其体外抗疟活性和细胞毒性进行了系统评价。其中，JX35对野生型和耐多药寄生虫株均表现出强效抑制作用，对寄生虫的所有生命周期包括血液期、肝脏期和配子体期均表现出显着的体内杀灭作用，表明其在同时治疗、化学预防和阻断疟疾传播。与quisinostat相比，JX35具有更强的抗疟功效、更充分的安全性和良好的药代动力学特性。此外，通过分子对接研究、诱导Pf HDAC1/2 敲低试验和Pf HDAC1 酶抑制试验的机理研究共同表明JX35的抗疟靶点是Pf HDAC1。总之，我们发现了有希望的候选Pf HDAC1 抑制剂JX35，它显示出比 quisinostat 更强的三阶段抗疟作用和更低的毒性。
• Therapeutic agents I
  申请人：Evertsson Emma

  公开号：US20070185079A1

  公开（公告）日：2007-08-09

  Compounds of formula(I), processes for preparing such compounds, their use in the treatment of obesity, psychiatric disorders, cognitive disorders, memory disorders, schizophrenia, epilepsy, and related conditions, and neurological disorders such as dementia, multiple sclerosis, Parkinson's disease, Huntington's chorea and Alzheimer's disease and pain related disorders, and pharmaceutical compositions containing them.

  化合物的公式(I)，制备这些化合物的过程，它们在治疗肥胖症、精神障碍、认知障碍、记忆障碍、精神分裂症、癫痫和相关疾病以及神经系统疾病如痴呆、多发性硬化症、帕金森病、亨廷顿舞蹈症和阿尔茨海默病以及与疼痛有关的疾病中的应用，以及含有它们的制药组合物。
• THERAPEUTIC AGENTS I
  申请人：AstraZeneca AB

  公开号：EP1706384A1

  公开（公告）日：2006-10-04