N-(3-methyl-5-isoxazolyl)-3-oxobutanamide | 882610-77-7

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: N-(3-methyl-5-isoxazolyl)-3-oxobutanamide
• 英文别名: N-(5-methyl-3-isoxazolyl)-3-oxobutanamide；N-(5-methyl-1,2-oxazol-3-yl)-3-oxobutanamide
• CAS: 882610-77-7
• 化学式: C₈H₁₀N₂O₃
• mdl: MFCD08691223
• 分子量: 182.179
• InChiKey: LHSSBYKOOGOGOY-UHFFFAOYSA-N

物化性质

• 沸点：
  407.3±35.0 °C(Predicted)
• 密度：
  1.256±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  13
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.375
• 拓扑面积：
  72.2
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-(3-methyl-5-isoxazolyl)-3-oxobutanamide 在 aluminum oxide 、 bismuth subnitrate 、 ammonium acetate 作用下， 以 氯仿 为溶剂， 反应 0.5h， 生成 2,6-Dimethyl-4-phenyl-pyridine-3,5-dicarboxylic acid bis-[(5-methyl-isoxazol-3-yl)-amide]
  参考文献：
  名称：

  改进的 Hantzsch 法固载合成异恶唑取代的 1,4-二氢吡啶及其芳构化

  摘要：

  摘要 异恶唑取代的 Hantzsch 1,4-二氢吡啶的合成首次通过改进的 Hantzsch 程序通过在中性氧化铝载体上使用酮酰胺代替酮酯以优异的产率合成。通过使用吸附在酸性氧化铝上的碱式硝酸铋 (BiONO3) 在环境温度下将这些 1,4-二氢吡啶以高产率芳构化为相应的吡啶。

  DOI：

  10.1080/15459620500408884
• 作为产物：
  描述：

  3-氨基-5-甲基异恶唑 、 2,2,6-三甲基-4H-1,3-二英-4-酮 以 5,5-dimethyl-1,3-cyclohexadiene 为溶剂， 以91%的产率得到N-(3-methyl-5-isoxazolyl)-3-oxobutanamide
  参考文献：
  名称：

  Design and synthesis of novel 3,5-bis-N-(aryl/heteroaryl) carbamoyl-4-aryl-1,4-dihydropyridines as small molecule BACE-1 inhibitors

  摘要：

  Alzheimer disease (AD) is a neuronal dementia for which no treatment has been consolidated yet. Major pathologic hallmark of AD is the aggregated extracellular amyloid-beta plaques in the brains of disease sufferers. A beta-peptide is a major component of amyloid plaques and is produced from amyloid precursor protein (APP) via the proteolysis action. An aspartyl protease known as beta-site amyloid precursor protein cleaving enzyme (BACE-1) is responsible for this proteolytic action. Distinctive role of BACE-1 in AD pathogenesis has made it a validated target to develop anti-Alzheimer agents. Our structure-based virtual screening method led to the synthesis of novel 3,5-bis-N-(aryl/heteroaryl) carbamoyl-4-aryl-1,4-dihydropyridine BACE-1 inhibitors (6a-6p; in vitro hits). Molecular docking and DFT-based ab initio studies using B3LYP functional in association with triple-zeta basis set (TZV) proposed binding mode and binding energies of ligands in the active site of the receptor. In vitro BACE-1 inhibitory activities were determined by enzymatic fluorescence resonance energy transfer (FRET) assay. Most of the synthesized dihydropyridine scaffolds were active against BACE-1 while 6d, 6k, 6n and 6a were found to be the most potent molecules with IC50 values of 4.21, 4.27, 4.66 and 6.78 mu M, respectively. Superior BACE-1 inhibitory activities were observed for dihydropyridine derivatives containing fused/nonfused thiazole containing groups, possibly attributing to the additional interactions with S2-S3 subpocket residues. Relatively reliable correlation between calculated binding energies and experimental BACE-1 inhibitory activities was achieved (R-2 = 0.51). Moreover, compounds 6d, 6k, 6n and 6a exhibited relatively no calcium channel blocking activity with regard to nifedipine suggesting them as appropriate candidates for further modification(s) to BACE-1 inhibitory scaffolds. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.09.033

文献信息

• An efficient and modified biginelli one-pot synthesis of new isoxazole substitted 3,4-dihydropyrimidin-2(1<i>H</i>)-ones and thiones catalyzed by VCl₃
  作者：E. Rajanarendar、P. Ramesh、G. Mohan、E. Kalyan Rao

  DOI：10.1002/jhet.5570440235

  日期：2007.3

  An efficient and modified Biginelli one-pot synthesis of new-isoxazole substituted 3,4-dihydropyrimidin-2(1H)-ones and thiones from aromatic aldehydes, ketoamide and urea/thiourea in acetonitrile using VCl3 as the catalyst is described.

  描述了一种高效且改良的Biginelli一锅法，使用VCl 3作为催化剂，从乙醛中的芳族醛，酮酰胺和尿素/硫脲，高效合成一新的异恶唑取代的3,4-二氢嘧啶-2（1 H）-酮和硫酮。
• Rajanarendar; Ramu; Karunakar, Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 2004, vol. 43, # 11, p. 2488 - 2490
  作者：Rajanarendar、Ramu、Karunakar

  DOI：——

  日期：——