Ethyl 6-amino-5-cyano-2-methyl-1,4-dihydro-4,4'-bipyridine-3-carboxylate | 299198-07-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: Ethyl 6-amino-5-cyano-2-methyl-1,4-dihydro-4,4'-bipyridine-3-carboxylate
• 英文别名: ethyl 6-amino-5-cyano-2-methyl-4-pyridin-4-yl-1,4-dihydropyridine-3-carboxylate
• CAS: 299198-07-5
• 化学式: C₁₅H₁₆N₄O₂
• 分子量: 284.318
• InChiKey: YSKGOJNCVBQFRF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  101
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  Ethyl 6-amino-5-cyano-2-methyl-1,4-dihydro-4,4'-bipyridine-3-carboxylate 、 环己酮 在 aluminum (III) chloride 作用下， 以 1,2-二氯乙烷 为溶剂， 反应 15.0h， 以90%的产率得到Ethyl 5-amino-2-methyl-4-pyridin-4-yl-1,4,6,7,8,9-hexahydrobenzo[b][1,8]naphthyridine-3-carboxylate
  参考文献：
  名称：

  Tacripyrines, the First Tacrine−Dihydropyridine Hybrids, as Multitarget-Directed Ligands for the Treatment of Alzheimer’s Disease

  摘要：

  Tacripyrines (1-14) have been designed by combining an ACNE inhibitor (tacrine) with a calcium antagonist such as nimodipine and are targeted to develop a multitarget therapeutic strategy to confront AD. Tacripyrines are selective and potent ACNE inhibitors in the nanomolar range. The mixed type inhibition of hAChE activity of compound 11 (IC50 105 +/- 15 nM) is associated to a 30.7 +/- 8.6% inhibition of the proaggregating action of ACNE on the A beta and a moderate inhibition of A beta self-aggregation (34.9 +/- 5.4%). Molecular modeling indicates that binding of compound 11 to the ACNE PAS mainly involves the (R)-11 enantiomer, which also agrees with the noncompetitive inhibition mechanism exhibited by p-methoxytacripyrine 11. Tacripyrines are neuroprotective agents, show moderate Ca2+ channel blocking effect, and cross the blood-brain barrier, emerging as lead candidates for treating AD.

  DOI：

  10.1021/jm801292b
• 作为产物：
  描述：

  ethyl 2-(4-pyridylmethylene)acetoacetate 、 2-氰基乙脒酸乙酯盐酸盐 在 乙酸铵 作用下， 以 甲醇 为溶剂， 反应 0.5h， 以66%的产率得到Ethyl 6-amino-5-cyano-2-methyl-1,4-dihydro-4,4'-bipyridine-3-carboxylate
  参考文献：
  名称：

  Synthesis of 6-amino-1,4-dihydropyridines that prevent calcium overload and neuronal death

  摘要：

  The synthesis and pharmacology of 6-amino-1,4-dihydropyridines, such as ethyl 6-amino-4-aryl-5-cyano-1,4-dihydro-2-methyl-3-pyridinecarboxylic acids (3-16) and 2-amino-4-aryl-7,7-dimethyl-5-oxo-1,4,5,6,7,8-hexahydro-3-quinolinenitriles (17-21) are described. Compounds 18 and 21, at the concentration of 0.3 mu M, proved to be the best blockers of the [Ca2+] overload induced by depolarization with high [K+] of SH-SY5Y neuroblastoma cells, with values of 63.8% and 50.4%, respectively. Most of the compounds induced a remarkable neuroprotective effect against toxicity caused by high [K+]-elicited [Ca2+] overload, and against H2O2-generated free radicals, in SH-SY5Y cells. (c) 2007 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2007.06.001

文献信息

• Tacripyrines, the First Tacrine−Dihydropyridine Hybrids, as Multitarget-Directed Ligands for the Treatment of Alzheimer’s Disease
  作者：José Marco-Contelles、Rafael León、Cristóbal de los Ríos、Abdelouahid Samadi、Manuela Bartolini、Vincenza Andrisano、Oscar Huertas、Xavier Barril、F. Javier Luque、María I. Rodríguez-Franco、Beatriz López、Manuela G. López、Antonio G. García、María do Carmo Carreiras、Mercedes Villarroya

  DOI：10.1021/jm801292b

  日期：2009.5.14

  Tacripyrines (1-14) have been designed by combining an ACNE inhibitor (tacrine) with a calcium antagonist such as nimodipine and are targeted to develop a multitarget therapeutic strategy to confront AD. Tacripyrines are selective and potent ACNE inhibitors in the nanomolar range. The mixed type inhibition of hAChE activity of compound 11 (IC50 105 +/- 15 nM) is associated to a 30.7 +/- 8.6% inhibition of the proaggregating action of ACNE on the A beta and a moderate inhibition of A beta self-aggregation (34.9 +/- 5.4%). Molecular modeling indicates that binding of compound 11 to the ACNE PAS mainly involves the (R)-11 enantiomer, which also agrees with the noncompetitive inhibition mechanism exhibited by p-methoxytacripyrine 11. Tacripyrines are neuroprotective agents, show moderate Ca2+ channel blocking effect, and cross the blood-brain barrier, emerging as lead candidates for treating AD.
• Synthesis of 6-amino-1,4-dihydropyridines that prevent calcium overload and neuronal death
  作者：Rafael León、Cristóbal de los Ríos、José Marco-Contelles、Manuela G. López、Antonio G. García、Mercedes Villarroya

  DOI：10.1016/j.ejmech.2007.06.001

  日期：2008.3

  The synthesis and pharmacology of 6-amino-1,4-dihydropyridines, such as ethyl 6-amino-4-aryl-5-cyano-1,4-dihydro-2-methyl-3-pyridinecarboxylic acids (3-16) and 2-amino-4-aryl-7,7-dimethyl-5-oxo-1,4,5,6,7,8-hexahydro-3-quinolinenitriles (17-21) are described. Compounds 18 and 21, at the concentration of 0.3 mu M, proved to be the best blockers of the [Ca2+] overload induced by depolarization with high [K+] of SH-SY5Y neuroblastoma cells, with values of 63.8% and 50.4%, respectively. Most of the compounds induced a remarkable neuroprotective effect against toxicity caused by high [K+]-elicited [Ca2+] overload, and against H2O2-generated free radicals, in SH-SY5Y cells. (c) 2007 Elsevier Masson SAS. All rights reserved.