2-Amino-7,7-dimethyl-5-oxo-4-pyridin-4-yl-1,4,6,8-tetrahydroquinoline-3-carbonitrile | 1022149-98-9

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 2-Amino-7,7-dimethyl-5-oxo-4-pyridin-4-yl-1,4,6,8-tetrahydroquinoline-3-carbonitrile
• CAS: 1022149-98-9
• 化学式: C₁₇H₁₈N₄O
• 分子量: 294.356
• InChiKey: UGOHRMBPPRWOAG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  22
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  91.8
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-Amino-7,7-dimethyl-5-oxo-4-pyridin-4-yl-1,4,6,8-tetrahydroquinoline-3-carbonitrile 、 环己酮 在 三氯化铝 作用下， 以 1,2-二氯乙烷 为溶剂， 反应 4.0h， 以88%的产率得到11-Amino-3,3-dimethyl-12-pyridin-4-yl-2,4,5,7,8,9,10,12-octahydroquinolino[2,3-b]quinolin-1-one
  参考文献：
  名称：

  New tacrine-dihydropyridine hybrids that inhibit acetylcholinesterase, calcium entry, and exhibit neuroprotection properties

  摘要：

  In this communication, we describe the synthesis and biological evaluation of tacripyrimedones 1-5, a series of new tacrine-1,4-dihydropyridine hybrids bearing the general structure of 11-amino-12-aryl-3,3- dimethyl-3,4,5,7,8,9,10,12-octahydrodibenzo[b,g][1,8]naphthyridine-1(2H)-one. These multifunctional compounds are moderately potent and selective AChEIs, with no activity toward BuChE. Kinetic analysis and molecular modeling studies point out that the new compounds preferentially bind the peripheral anionic site of AChE. In addition, compounds 1-5 show an excellent neuroprotective pro. le, and a moderate blocking effect of L-type voltage-dependent calcium channels due to the mitigation of [Ca2+]elevation elicited by K+ depolarization. Therefore, they represent a new family of molecules with potential therapeutic application for the treatment of Alzheimer's disease. (c) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2008.07.005
• 作为产物：
  描述：

  4-pyridinylmethylenepropanedinitrile 、 3-氨基-5,5-二甲基-2-环己烯-1-酮 在 乙酸铵 作用下， 以 甲醇 为溶剂， 反应 3.5h， 以71%的产率得到2-Amino-7,7-dimethyl-5-oxo-4-pyridin-4-yl-1,4,6,8-tetrahydroquinoline-3-carbonitrile
  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

• 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.
• New tacrine-dihydropyridine hybrids that inhibit acetylcholinesterase, calcium entry, and exhibit neuroprotection properties
  作者：Rafael León、Cristóbal de los Ríos、José Marco-Contelles、Oscar Huertas、Xavier Barril、F. Javier Luque、Manuela G. López、Antonio G. García、Mercedes Villarroya

  DOI：10.1016/j.bmc.2008.07.005

  日期：2008.8

  In this communication, we describe the synthesis and biological evaluation of tacripyrimedones 1-5, a series of new tacrine-1,4-dihydropyridine hybrids bearing the general structure of 11-amino-12-aryl-3,3- dimethyl-3,4,5,7,8,9,10,12-octahydrodibenzo[b,g][1,8]naphthyridine-1(2H)-one. These multifunctional compounds are moderately potent and selective AChEIs, with no activity toward BuChE. Kinetic analysis and molecular modeling studies point out that the new compounds preferentially bind the peripheral anionic site of AChE. In addition, compounds 1-5 show an excellent neuroprotective pro. le, and a moderate blocking effect of L-type voltage-dependent calcium channels due to the mitigation of [Ca2+]elevation elicited by K+ depolarization. Therefore, they represent a new family of molecules with potential therapeutic application for the treatment of Alzheimer's disease. (c) 2008 Elsevier Ltd. All rights reserved.