diethyl 4-i-propylanilinomethylenemalonate | 64321-60-4

• 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: diethyl 4-i-propylanilinomethylenemalonate
• 英文别名: Diethyl ({[4-(propan-2-yl)phenyl]amino}methylidene)propanedioate；diethyl 2-[(4-propan-2-ylanilino)methylidene]propanedioate
• CAS: 64321-60-4
• 化学式: C₁₇H₂₃NO₄
• 分子量: 305.374
• InChiKey: DKHKKXPGIKQIIZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  22
• 可旋转键数：
  9
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  64.6
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  diethyl 4-i-propylanilinomethylenemalonate 以 二苯醚 为溶剂， 反应 16.0h， 生成 ethyl 6-isopropyl-4-oxo-1,4-dihydroquinoline-3-carboxylate
  参考文献：
  名称：

  Investigations on the 4-Quinolone-3-carboxylic Acid Motif. 2. Synthesis and Structure−Activity Relationship of Potent and Selective Cannabinoid-2 Receptor Agonists Endowed with Analgesic Activity in Vivo

  摘要：

  Quinolone-3-carboxamides 11 bearing at position 5, 6, 7, or 8 diverse substituents such as halides, alkyl, aryl, alkoxy, and aryloxy groups differing in their steric/electronic properties, were prepared. The new compounds were tested in vitro for CB1 and CB2 receptor affinity in comparison with the reference compounds rimonabant and SR144528. The tested compounds exhibited CB2 affinity in the ran, e from 55.9 to 0.8 nM and CB1 affinity in the range from > 10 000 to 5.3 nM, with selectivity indeces [K-i(CB1)/K-i(CB2)] varying from > 2666.6 to 1.23. On the basis of the structure-selectivity relationship developed, the presence of a substituent at C6/C8 or C7 well accounts for the high or low CB2 selectivity, respectively. Compound 11c, characterized by high CB2 affinity and selectivity, showed analgesic activity in the formalin test of acute peripheral and inflammatory pain in mice as a result of selective CB2 agonistic activity.

  DOI：

  10.1021/jm800552f
• 作为产物：
  描述：

  4-异丙基苯胺 、 乙氧基甲叉丙二酸二乙酯 反应 2.0h， 以100%的产率得到diethyl 4-i-propylanilinomethylenemalonate
  参考文献：
  名称：

  4-Quinolone Derivatives:  High-Affinity Ligands at the Benzodiazepine Site of Brain GABA_A Receptors. Synthesis, Pharmacology, and Pharmacophore Modeling

  摘要：

  The 3-ethoxycarbonyl-4-quinolone compound I has previously been identified via a database search as an interesting lead compound for ligand binding at the benzodiazepine site of GABA(A) receptors (Kahnberg et al. J. Mol. Graphics Modelling 2004, 23, 253-261). Pharmacophore-guided optimization of this lead compound yielded a number of high-affinity ligands for the benzodiazepine site including compounds 20 and 23-25 displaying sub-nanomolar affinities. A few of the compounds have been tested on the alpha(1)beta(2)gamma(2s) and alpha(3)beta(2)gamma(2s) GABA(A) receptor subtypes, and two of the compounds (5 and 19) display selectivity for alpha(1) versus alpha(3)-containing receptors by a factor of 22 and 27, respectively. This selectivity for alpha(1)beta(2)gamma(2s) is in the same range as that for the well-known alpha(1) subunit selective compound zolpidem.

  DOI：

  10.1021/jm058057p

文献信息

• 4-Quinolone Derivatives:  High-Affinity Ligands at the Benzodiazepine Site of Brain GABA_A Receptors. Synthesis, Pharmacology, and Pharmacophore Modeling
  作者：Erik Lager、Pierre Andersson、Jakob Nilsson、Ingrid Pettersson、Elsebet Østergaard Nielsen、Mogens Nielsen、Olov Sterner、Tommy Liljefors

  DOI：10.1021/jm058057p

  日期：2006.4.1

  The 3-ethoxycarbonyl-4-quinolone compound I has previously been identified via a database search as an interesting lead compound for ligand binding at the benzodiazepine site of GABA(A) receptors (Kahnberg et al. J. Mol. Graphics Modelling 2004, 23, 253-261). Pharmacophore-guided optimization of this lead compound yielded a number of high-affinity ligands for the benzodiazepine site including compounds 20 and 23-25 displaying sub-nanomolar affinities. A few of the compounds have been tested on the alpha(1)beta(2)gamma(2s) and alpha(3)beta(2)gamma(2s) GABA(A) receptor subtypes, and two of the compounds (5 and 19) display selectivity for alpha(1) versus alpha(3)-containing receptors by a factor of 22 and 27, respectively. This selectivity for alpha(1)beta(2)gamma(2s) is in the same range as that for the well-known alpha(1) subunit selective compound zolpidem.
• Investigations on the 4-Quinolone-3-carboxylic Acid Motif. 2. Synthesis and Structure−Activity Relationship of Potent and Selective Cannabinoid-2 Receptor Agonists Endowed with Analgesic Activity in Vivo
  作者：Serena Pasquini、Lorenzo Botta、Teresa Semeraro、Claudia Mugnaini、Alessia Ligresti、Enza Palazzo、Sabatino Maione、Vincenzo Di Marzo、Federico Corelli

  DOI：10.1021/jm800552f

  日期：2008.8.1

  Quinolone-3-carboxamides 11 bearing at position 5, 6, 7, or 8 diverse substituents such as halides, alkyl, aryl, alkoxy, and aryloxy groups differing in their steric/electronic properties, were prepared. The new compounds were tested in vitro for CB1 and CB2 receptor affinity in comparison with the reference compounds rimonabant and SR144528. The tested compounds exhibited CB2 affinity in the ran, e from 55.9 to 0.8 nM and CB1 affinity in the range from > 10 000 to 5.3 nM, with selectivity indeces [K-i(CB1)/K-i(CB2)] varying from > 2666.6 to 1.23. On the basis of the structure-selectivity relationship developed, the presence of a substituent at C6/C8 or C7 well accounts for the high or low CB2 selectivity, respectively. Compound 11c, characterized by high CB2 affinity and selectivity, showed analgesic activity in the formalin test of acute peripheral and inflammatory pain in mice as a result of selective CB2 agonistic activity.