(5-氯-2-甲基-苯基)-(4,6-二氯-[1,3,5]三嗪-2-基)-胺 | 102878-02-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: (5-氯-2-甲基-苯基)-(4,6-二氯-[1,3,5]三嗪-2-基)-胺
• 英文名称: 2,4-Dichlor-6-<5-chlor-2-methyl-anilino>-s-triazin
• 英文别名: (5-chloro-2-methyl-phenyl)-(4,6-dichloro-[1,3,5]triazin-2-yl)-amine；(5-chloro-2-methyl-phenyl)-(dichloro-[1,3,5]triazin-2-yl)-amine；(5-Chlor-2-methyl-phenyl)-(dichlor-[1,3,5]triazin-2-yl)-amin；4,6-dichloro-N-(5-chloro-2-methylphenyl)-1,3,5-triazin-2-amine
• CAS: 102878-02-4
• 化学式: C₁₀H₇Cl₃N₄
• 分子量: 289.551
• InChiKey: BPOPGIUXEUTLBL-UHFFFAOYSA-N

物化性质

• 熔点：
  192-193 °C
• 沸点：
  464.5±55.0 °C(Predicted)
• 密度：
  1.546±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  50.7
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (5-氯-2-甲基-苯基)-(4,6-二氯-[1,3,5]三嗪-2-基)-胺 在 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 1,4-二氧六环 为溶剂， 反应 1.0h， 生成 4-[4-(5-chloro-2-methyl-phenylamino)-6-pentylamino-[1,3,5]triazin-2-yl]-piperazine-1-carboxylic acid tert-butyl ester
  参考文献：
  名称：

  Elaborate ligand-based modeling and subsequent synthetic exploration unveil new nanomolar Ca2+/calmodulin-dependent protein kinase II inhibitory leads

  摘要：

  Ca2+/calmodulin-dependent protein kinase II (CaMKII) has been recently implicated in cardiovascular diseases and hypertension prompting several attempts to discover and optimize new CaMKII delta inhibitors. Towards this end we explored the pharmacophoric space of 88 CaMKII delta inhibitors using nine diverse sets of inhibitors to identify high quality pharmacophores. Subsequently, genetic algorithm and multiple linear regression analysis were employed to select an optimal combination of pharmacophoric models and 2D physicochemical descriptors capable of accessing self-consistent quantitative structure-activity relationship (QSAR) of optimal predictive potential (r(72)(2) = 0.70, F = 18.19, r(LOO)(2) 0.71, r(PRESS)(2) against 16 external test inhibitors = 0.60). Three orthogonal pharmacophores emerged in the QSAR equation suggesting the existence of at least three binding modes accessible to ligands within CaMKII delta binding pocket. Receiver operating characteristic (ROC) curves analysis established the validity of QSAR-selected pharmacophores. We employed the pharmacophoric models and associated QSAR equation to screen the national cancer institute (NCI) list of compounds. In silico screening identified nanomolar and low micromolar inhibitors. The most potent hits exhibited IC50 values of 20 and 82 nM. The best pharmacophoric model (Hypo8/31) was employed to guide the synthesis of novel triazine-based CaMKII delta inhibitors, of which the most potent illustrated an IC50 value of 154 nM against CaMKII delta. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.10.071
• 作为产物：
  描述：

  三聚氯氰 、 5-氯邻甲苯胺 以 丙酮 为溶剂， 反应 4.0h， 以74%的产率得到(5-氯-2-甲基-苯基)-(4,6-二氯-[1,3,5]三嗪-2-基)-胺
  参考文献：
  名称：

  Elaborate ligand-based modeling and subsequent synthetic exploration unveil new nanomolar Ca2+/calmodulin-dependent protein kinase II inhibitory leads

  摘要：

  Ca2+/calmodulin-dependent protein kinase II (CaMKII) has been recently implicated in cardiovascular diseases and hypertension prompting several attempts to discover and optimize new CaMKII delta inhibitors. Towards this end we explored the pharmacophoric space of 88 CaMKII delta inhibitors using nine diverse sets of inhibitors to identify high quality pharmacophores. Subsequently, genetic algorithm and multiple linear regression analysis were employed to select an optimal combination of pharmacophoric models and 2D physicochemical descriptors capable of accessing self-consistent quantitative structure-activity relationship (QSAR) of optimal predictive potential (r(72)(2) = 0.70, F = 18.19, r(LOO)(2) 0.71, r(PRESS)(2) against 16 external test inhibitors = 0.60). Three orthogonal pharmacophores emerged in the QSAR equation suggesting the existence of at least three binding modes accessible to ligands within CaMKII delta binding pocket. Receiver operating characteristic (ROC) curves analysis established the validity of QSAR-selected pharmacophores. We employed the pharmacophoric models and associated QSAR equation to screen the national cancer institute (NCI) list of compounds. In silico screening identified nanomolar and low micromolar inhibitors. The most potent hits exhibited IC50 values of 20 and 82 nM. The best pharmacophoric model (Hypo8/31) was employed to guide the synthesis of novel triazine-based CaMKII delta inhibitors, of which the most potent illustrated an IC50 value of 154 nM against CaMKII delta. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.10.071

文献信息

• DEFAUNATION METHOD
  申请人：MALLINCKRODT VETERINARY LIMITED

  公开号：EP0661976A1

  公开（公告）日：1995-07-12
• EP0661976A4
  申请人：——

  公开号：EP0661976A4

  公开（公告）日：1994-07-20
• US5561131A
  申请人：——

  公开号：US5561131A

  公开（公告）日：1996-10-01
• [EN] DEFAUNATION METHOD
  申请人：PITMAN-MOORE AUSTRALIA LIMITED

  公开号：WO1993002680A1

  公开（公告）日：1993-02-18

  (EN) The use of triazine compounds of formula (I) for the preparation of a medicament for use in a method for defaunation of ruminant animals, in which an effective amount of the compound is administered to the animals. Defaunation is the selective removal of protozoa from the rumen in preference to removal or deactivation of bacteria. In formula (I): x = 1 or 2, R = H or lower alkyl, Ar = phenyl, diphenyl, naphthyl, anthracyl or phenanthryl radicals and substituted derivatives thereof.(FR) Utilisation de composés de triazine de la formule (I) pour la préparation d'un médicament utilisé dans un procédé de défaunation de ruminants, selon lequel une quantité efficace du composé est administrée aux animaux. La défaunation consiste à enlever de préférence sélectivement des protozoaires de la panse au lieu d'enlever ou de désactiver des bactéries. Dans la formule (I) x = 1 ou 2, R = H ou alkyle inférieur, Ar = radicaux de phényle, diphényle, naphtyle, anthracyle ou phénanthryle et dérivés substitués de ces radicaux.
• Elaborate ligand-based modeling and subsequent synthetic exploration unveil new nanomolar Ca2+/calmodulin-dependent protein kinase II inhibitory leads
  作者：Rand Shahin、Mutasem O. Taha

  DOI：10.1016/j.bmc.2011.10.071

  日期：2012.1

  Ca2+/calmodulin-dependent protein kinase II (CaMKII) has been recently implicated in cardiovascular diseases and hypertension prompting several attempts to discover and optimize new CaMKII delta inhibitors. Towards this end we explored the pharmacophoric space of 88 CaMKII delta inhibitors using nine diverse sets of inhibitors to identify high quality pharmacophores. Subsequently, genetic algorithm and multiple linear regression analysis were employed to select an optimal combination of pharmacophoric models and 2D physicochemical descriptors capable of accessing self-consistent quantitative structure-activity relationship (QSAR) of optimal predictive potential (r(72)(2) = 0.70, F = 18.19, r(LOO)(2) 0.71, r(PRESS)(2) against 16 external test inhibitors = 0.60). Three orthogonal pharmacophores emerged in the QSAR equation suggesting the existence of at least three binding modes accessible to ligands within CaMKII delta binding pocket. Receiver operating characteristic (ROC) curves analysis established the validity of QSAR-selected pharmacophores. We employed the pharmacophoric models and associated QSAR equation to screen the national cancer institute (NCI) list of compounds. In silico screening identified nanomolar and low micromolar inhibitors. The most potent hits exhibited IC50 values of 20 and 82 nM. The best pharmacophoric model (Hypo8/31) was employed to guide the synthesis of novel triazine-based CaMKII delta inhibitors, of which the most potent illustrated an IC50 value of 154 nM against CaMKII delta. (C) 2011 Elsevier Ltd. All rights reserved.