N-(2-bromobenzyl)-2-cyanoacetamide | 566926-28-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N-(2-bromobenzyl)-2-cyanoacetamide
• 英文别名: N-[(2-bromophenyl)methyl]-2-cyanoacetamide
• CAS: 566926-28-1
• 化学式: C₁₀H₉BrN₂O
• mdl: MFCD14661192
• 分子量: 253.098
• InChiKey: JDZXBBYQHQWJAE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  14
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  52.9
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  N-(2-bromobenzyl)-2-cyanoacetamide 、 7-羟基-4-甲基-2-氧代-2H-色烯-8-甲醛 在 三乙胺 作用下， 以 乙醇 为溶剂， 以73%的产率得到N-(2-bromobenzyl)-8-imino-4-methyl-2-oxo-2H,8H-pyrano[2,3-f]chromene-9-carboxamide
  参考文献：
  名称：

  Synthesis, pharmacological assessment, molecular modeling and in silico studies of fused tricyclic coumarin derivatives as a new family of multifunctional anti-Alzheimer agents

  摘要：

  A series of fused tricyclic coumarin derivatives bearing iminopyran ring connected to various amido moieties were developed as potential multifunctional anti-Alzheimer agents for their cholinesterase inhibitory and radical scavenging activities. In vitro studies revealed that most of these compounds exhibited high inhibitory activity on acetylcholinesterase (AChE), with IC50 values ranging from 0.003 to 0.357 mu M which is 2-220 folds more potent than the positive control, galantamine. Their inhibition selectivity against AChE over butyrylcholinesterase (BuChE) has increased about 194 fold compared with galantamine. The developed compounds also showed potent ABTS radical scavenging activity (IC50 7.98 -15.99 mu M). Specifically, the most potent AChE inhibitor 6n (IC50 0.003 +/- 0.0007 mu M) has an excellent antioxidant profile as determined by the ABTS method (IC50 7.98 0.77 mu M). Moreover, cell viability studies in SK N SH cells showed that the compounds 6m-q have significant neuroprotective effects against H2O2-induced cell death, and are not neurotoxic at all concentrations except 6n and 6q. The kinetic analysis of compound 6n proved that it is a mixed-type inhibitor for EeAChE (K-i1 0.0103 mu M and K-i2 0.0193 mu M). Accordingly, the molecular modeling study demonstrated that 6m-q with substituted benzyl amido moiety possessed an optimal docking pose with interactions at catalytic active site (CAS) and peripheral anionic site (PAS) of AChE simultaneously and thereby they might prevent aggregation of A beta induced by AChE. Furthermore, in silico ADMET prediction studies indicated that these compounds satisfied all the characteristics of CNS acting drugs. Most active inhibitor 6n is permeable to BBB as determined in the in vivo brain AChE activity. To sum up, the multipotent therapuetic profile of these novel tricyclic coumarins makes them promising leads for developing anti-Alzheimer agents. (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.10.046
• 作为产物：
  描述：

  邻溴苄胺 、 氰乙酸乙酯 生成 N-(2-bromobenzyl)-2-cyanoacetamide
  参考文献：
  名称：

  8-亚氨基-2-氧代-2H，8H-吡喃并[2,3-f]色烯类似物的合成，生物学评估和分子对接：新型双重AChE抑制剂可作为治疗阿尔茨海默氏病的潜在药物

  摘要：

  阿尔茨海默氏病的发作和发展与多种复杂生理过程的失调有关，因此成功的治疗方法应解决多个目标。根据这种现代范式，合成了一系列8-亚氨基-2-氧代-2 H，8 H-吡喃[2,3- f ]色烯类似物（4a – q）并评估了它们在多靶点上的活性。乙酰胆碱酯酶，丁酰胆碱酯酶（BuChE的），2,2'-连氮基-双（3-乙基苯并噻唑-6-磺酸）（ABTS）基团，和淀粉样蛋白β肽（A β）阿尔茨海默氏病治疗的特定目标。大多数合成的化合物在低n m浓度下表现出显着的乙酰胆碱酯酶抑制活性，并具有良好的ABTS自由基清除活性，但是，没有BuChE抑制活性的证据。其中，3-溴苄酰胺衍生物4m表现出最好的乙酰胆碱酯酶抑制活性，IC 50值为13±1.4 n m，是参比药物加兰他敏的51倍。动力学和分子对接研究表明4m是混合型抑制剂，同时与乙酰胆碱酯酶的催化活性和外围阴离子位点结合。五种化合物4e，4f，4g，4j和4k的抗氧化活性比trolox高1

  DOI：

  10.1111/cbdd.12732

文献信息

• Modulators of LXR
  申请人：——

  公开号：US20030181420A1

  公开（公告）日：2003-09-25

  Compounds, compositions and methods for modulating the activity of nuclear receptors are provided. In particular, heterocyclic compounds are provided for modulating the activity of nuclear receptors, including liver X receptor (LXR) and orphan nuclear receptors. In certain embodiments, the compounds are N-substituted pyridones.

  提供了用于调节核受体活性的化合物、组合物和方法。具体来说，提供了用于调节核受体活性的杂环化合物，包括肝X受体（LXR）和孤儿核受体。在某些实施方式中，这些化合物是N-取代吡啶酮。
• Aminoisoxazole derivatives active as kinase inhibitors
  申请人：Cavicchioli Marcello

  公开号：US20050059657A1

  公开（公告）日：2005-03-17

  Compounds (I) which are aminoisoxazole derivatives or pharmaceutically acceptable salts thereof, together with pharmaceutical compositions comprising them are disclosed; these compounds or compositions are useful in the treatment of diseases caused by and/or associated with an altered protein kinase activity such as cancer, cell proliferative disorders, Alzheimer's disease, viral infections, auto-immune diseases and neurodegenerative disorders.

  本发明涉及氨基异噁唑衍生物(I)或其药学上可接受的盐，以及包含它们的药物组合物。这些化合物或组合物在治疗由蛋白激酶活性改变引起和/或相关的疾病方面具有用途，例如癌症、细胞增殖性疾病、阿尔茨海默病、病毒感染、自身免疫性疾病和神经退行性疾病。
• Cyanoacetamides (IV): Versatile One-Pot Route to 2-Quinoline-3-carboxamides
  作者：Kan Wang、Eberhardt Herdtweck、Alexander Dömling

  DOI：10.1021/co3000133

  日期：2012.5.14

  Cyanoacetic acid derivatives are the starting materials for a plethora of multicomponent reaction (MCR) scaffolds. Herein, we describe scope of a valuable general protocol for the synthesis of arrays of 2-aminoquinoline-3-carboxamides from cyanoacetamides and 2-aminobenzaldehydes or heterocyclic derivatives via a Friedlander reaction variation. In many cases, the reactions involve a very convenient work up by simple precipitation and filtration. More than 40 new products are described. We foresee our protocol and the resulting derivatives becoming very valuable to greatly expanding the scaffold space of cyanoacetamide derivatives.
• Synthesis and biological evaluation of flavone-8-acrylamide derivatives as potential multi-target-directed anti Alzheimer agents and investigation of binding mechanism with acetylcholinesterase
  作者：Jeelan Basha Shaik、Daniel Pushparaju Yeggoni、Yelamanda Rao Kandrakonda、Mohan Penumala、Raveendra Babu Zinka、Kasi Viswanath Kotapati、Mark Manidhar Darla、Dinakara Rao Ampasala、Rajagopal Subramanyam、Damu Gangaiah Amooru

  DOI：10.1016/j.bioorg.2019.102960

  日期：2019.7

  In a search for novel multifunctional anti-Alzheimer agents, a congeneric set of seventeen flavone-8-acrylamide derivatives (8a-q) were synthesized and evaluated for their cholinesterase inhibitory, antioxidant, neuroprotective and modulation of A beta aggregation activities. The target compounds showed effective and selective inhibitory activity against the AChE over BuChE. In addition, the target compounds also showed moderate antioxidant activity and strong neuroprotective capacities, and accelerated dosage-dependently the A beta aggregation. Also, we presented here a complete study on the interaction of 8a, 8d, 8e, 8h and 8i with AChE. Through fluorescence emission studies, the binding sites number found to be 1, binding constants were calculated as 2.04 x 10(4), 2.22 x 10(4), 1.18 x 10(4), 9.8 x 10(3) and 3.2 x 10(4) M-1 and free energy change as -5.83, -5.91, -5.51, -5.41 and -6.12 kcal M-1 at 25 degrees C which were well agreed with the computational calculations indicating a strong binding affinity of flavones and AChE. Furthermore, the CD studies revealed that the secondary structure of AChE became partly unfolded upon binding with 8a, 8d, 8e, 8h and 8i.
• New Flavone-Cyanoacetamide Hybrids with a Combination of Cholinergic, Antioxidant, Modulation of β-Amyloid Aggregation, and Neuroprotection Properties as Innovative Multifunctional Therapeutic Candidates for Alzheimer’s Disease and Unraveling Their Mechanism of Action with Acetylcholinesterase
  作者：Shaik Jeelan Basha、Penumala Mohan、Daniel Pushparaju Yeggoni、Zinka Raveendra Babu、Palaka Bhagath Kumar、Ampasala Dinakara Rao、Rajagopal Subramanyam、Amooru Gangaiah Damu

  DOI：10.1021/acs.molpharmaceut.8b00041

  日期：2018.6.4

  In line with the modern multi-target-directed ligand paradigm of Alzheimer's disease (AD), a series of 19 compounds composed of flavone and cyanoacetamide groups have been synthesized and evaluated as multifunctional agents against AD. Biological evaluation demonstrated that compounds 7j, 7n, 7o, 7r, and 7s exhibited excellent inhibitory potency (ACNE, IC50 of 0.27 +/- 10.012 to 1.006 +/- 0.075 mu M) and good selectivity toward acetylcholinesterase, significant antioxidant activity, good modulation effects on self-induced A beta aggregation, low cytotoxicity, and neuroprotection in Havone-cyanoacetamide human neuroblastoma SK-N-SH cells. Further, an inclusive study on the interaction of 7j, 7n, 70, 7r, and 7s with AChE at physiological pH 7.2 using fluorescence, circular dichroism, and molecular docking methods suggested that these derivatives bind strongly to the peripheral anionic site of AChE mostly through hydrophobic interactions. Overall, the multifunctional profiles and strong AChE binding affinity highlight these compounds as promising prototypes for further pursuit of innovative multifunctional drugs for AD.