6-氨基-3,4-二氢-4-(2-甲基苯基)-1,3,5-三嗪-2(1H)-硫酮 | 1142208-15-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 三嗪类
• 中文名称: 6-氨基-3,4-二氢-4-(2-甲基苯基)-1,3,5-三嗪-2(1H)-硫酮
• 英文名称: 6-amino-4-(o-tolyl)-3,4-dihydro-1,3,5-triazine-2(1H)-thione
• 英文别名: 4-Amino-6-(2-methylphenyl)-1,6-dihydro-1,3,5-triazine-2-thiol；4-amino-2-(2-methylphenyl)-2,5-dihydro-1H-1,3,5-triazine-6-thione
• CAS: 1142208-15-8
• 化学式: C₁₀H₁₂N₄S
• 分子量: 220.298
• InChiKey: CIJFJBOOTBYJPA-UHFFFAOYSA-N

物化性质

• 沸点：
  374.7±52.0 °C(Predicted)
• 密度：
  1.41±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  15
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  94.5
• 氢给体数：
  3
• 氢受体数：
  2

安全信息

• 危险等级：
  IRRITANT

反应信息

• 作为产物：
  描述：

  脒基硫脲 、 2-甲基苯甲醛 在 硫酸 作用下， 反应 72.0h， 以66%的产率得到6-氨基-3,4-二氢-4-(2-甲基苯基)-1,3,5-三嗪-2(1H)-硫酮
  参考文献：
  名称：

  3,4-Dihydro-1,3,5-triazin-2(1H)-ones as the First Dual BACE-1/GSK-3β Fragment Hits against Alzheimer’s Disease

  摘要：

  One of the main obstacles toward the discovery of effective anti-Alzheimer drugs is the multifactorial nature of its etiopathology. Therefore, the use of multitarget-directed ligands has emerged as particularly suitable. Such ligands, able to modulate different neurodegenerative pathways, for example, amyloid and tau cascades, as well as cognitive and neurogenic functions, are fostered to come. In this respect, we report herein on the first class of BACE-1/GSK-3 beta dual inhibitors based on a 3,4-dihydro-1,3,5-triazin-2(1H)-one skeleton, whose hit compound 1 showed interesting properties in a preliminary investigation. Notably, compound 2, endowed with well-balanced potencies against the two isolated enzymes (IC50 of 16 and 7 mu M against BACE-1 and GSK-3 beta, respectively), displayed effective neuroprotective and neurogenic activities and no neurotoxicity in cell-based assays. It also showed good brain permeability in a pharmacokinetic assessment in mice. Overall, triazinone derivatives, thanks to the simultaneous modulation of multiple points of the diseased network, might emerge as suitable candidates to be tested in in vivo Alzheimer's disease models.

  DOI：

  10.1021/acschemneuro.5b00121

文献信息

• 3,4-Dihydro-1,3,5-triazin-2(1<i>H</i>)-ones as the First Dual BACE-1/GSK-3β Fragment Hits against Alzheimer’s Disease
  作者：Federica Prati、Angela De Simone、Andrea Armirotti、Maria Summa、Daniela Pizzirani、Rita Scarpelli、Sine Mandrup Bertozzi、Daniel I. Perez、Vincenza Andrisano、Ana Perez-Castillo、Barbara Monti、Francesca Massenzio、Letizia Polito、Marco Racchi、Piera Sabatino、Giovanni Bottegoni、Ana Martinez、Andrea Cavalli、Maria L. Bolognesi

  DOI：10.1021/acschemneuro.5b00121

  日期：2015.10.21

  One of the main obstacles toward the discovery of effective anti-Alzheimer drugs is the multifactorial nature of its etiopathology. Therefore, the use of multitarget-directed ligands has emerged as particularly suitable. Such ligands, able to modulate different neurodegenerative pathways, for example, amyloid and tau cascades, as well as cognitive and neurogenic functions, are fostered to come. In this respect, we report herein on the first class of BACE-1/GSK-3 beta dual inhibitors based on a 3,4-dihydro-1,3,5-triazin-2(1H)-one skeleton, whose hit compound 1 showed interesting properties in a preliminary investigation. Notably, compound 2, endowed with well-balanced potencies against the two isolated enzymes (IC50 of 16 and 7 mu M against BACE-1 and GSK-3 beta, respectively), displayed effective neuroprotective and neurogenic activities and no neurotoxicity in cell-based assays. It also showed good brain permeability in a pharmacokinetic assessment in mice. Overall, triazinone derivatives, thanks to the simultaneous modulation of multiple points of the diseased network, might emerge as suitable candidates to be tested in in vivo Alzheimer's disease models.