2-chloro-4-(3-chlorophenyl)-6-ethyl-1,3,5-triazine | 1606976-56-0

• 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: 2-chloro-4-(3-chlorophenyl)-6-ethyl-1,3,5-triazine
• 英文别名: 2-Chloro-4-(3-chlorophenyl)-6-ethyl-1,3,5-triazine
• CAS: 1606976-56-0
• 化学式: C₁₁H₉Cl₂N₃
• 分子量: 254.119
• InChiKey: MYJVBINQNKVKEL-UHFFFAOYSA-N

物化性质

• 沸点：
  447.7±47.0 °C(Predicted)
• 密度：
  1.329±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  38.7
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  对氨基苯乙腈 、 2-chloro-4-(3-chlorophenyl)-6-ethyl-1,3,5-triazine 在 溶剂黄146 作用下， 反应 1.0h， 以35 mg的产率得到2-(4-(4-(3-chlorophenyl)-6-ethyl-1,3,5-triazin-2-ylamino)phenyl)acetonitrile
  参考文献：
  名称：

  Discovery of triazines as selective PDE4B versus PDE4D inhibitors

  摘要：

  In this study we report a series of triazine derivatives that are potent inhibitors of PDE4B. We also provide a series of structure activity relationships that demonstrate the triazine core can be used to generate subtype selective inhibitors of PDE4B versus PDE4D. A high resolution co-crystal structure shows that the inhibitors interact with a C-terminal regulatory helix (CR3) locking the enzyme in an inactive 'closed' conformation. The results show that the compounds interact with both catalytic domain and CR3 residues. This provides the first structure-based approach to engineer PDE4B-selective inhibitors. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.06.002
• 作为产物：
  描述：

  3-氯苯腈 在 sodium methylate 、 三氯氧磷 作用下， 以 甲醇 、 乙腈 为溶剂， 反应 4.0h， 生成 2-chloro-4-(3-chlorophenyl)-6-ethyl-1,3,5-triazine
  参考文献：
  名称：

  Discovery of triazines as selective PDE4B versus PDE4D inhibitors

  摘要：

  In this study we report a series of triazine derivatives that are potent inhibitors of PDE4B. We also provide a series of structure activity relationships that demonstrate the triazine core can be used to generate subtype selective inhibitors of PDE4B versus PDE4D. A high resolution co-crystal structure shows that the inhibitors interact with a C-terminal regulatory helix (CR3) locking the enzyme in an inactive 'closed' conformation. The results show that the compounds interact with both catalytic domain and CR3 residues. This provides the first structure-based approach to engineer PDE4B-selective inhibitors. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.06.002

文献信息

• Design and Synthesis of Selective Phosphodiesterase 4D (PDE4D) Allosteric Inhibitors for the Treatment of Fragile X Syndrome and Other Brain Disorders
  作者：Mark E. Gurney、Richard A. Nugent、Xuesheng Mo、Janice A. Sindac、Timothy J. Hagen、David Fox、James M. O’Donnell、Chong Zhang、Ying Xu、Han-Ting Zhang、Vincent E. Groppi、Marc Bailie、Ronald E. White、Donna L. Romero、A. Samuel Vellekoop、Joel R. Walker、Matthew D. Surman、Lei Zhu、Robert F. Campbell

  DOI：10.1021/acs.jmedchem.9b00193

  日期：2019.5.23

  pyridine- and pyrimidine-based allosteric inhibitors are reported that achieve PDE4D subtype selectivity through recognition of a single amino acid difference on a key regulatory domain, known as UCR2, that opens and closes over the catalytic site for cAMP hydrolysis. The design and optimization of lead compounds was based on iterative analysis of X-ray crystal structures combined with metabolite identification

  据报道，新的基于吡啶和嘧啶的变构抑制剂通过识别关键调控域（称为 UCR2）上的单个氨基酸差异来实现 PDE4D 亚型选择性，该域在 cAMP 水解的催化位点上打开和关闭。先导化合物的设计和优化基于 X 射线晶体结构的迭代分析和代谢物鉴定。对 PDE4D 的活化二聚体形式的选择性在新物体识别的小鼠模型中提供了有效的记忆增强效果，与缺乏亚型选择性的早期 PDE4 抑制剂相比，具有更高的耐受性和更低的血管毒性。先导化合物 28 (BPN14770) 已进入治疗脆性 X 综合征的中期人类 2 期临床试验。
• HETEROARYL INHIBITORS OF PDE4
  申请人：Tetra Discovery Partners, LLC

  公开号：US20150119362A1

  公开（公告）日：2015-04-30

  The present invention relates to compounds and methods useful as inhibitors of phosphodiesterase 4 (PDE4) for the treatment or prevention of disease.

  本发明涉及化合物和方法，用于作为磷酸二酯酶4（PDE4）的抑制剂，用于治疗或预防疾病。
• Heteroaryl inhibitors of PDE4
  申请人：Tetra Discovery Partners, LLC

  公开号：US09221843B2

  公开（公告）日：2015-12-29

  The present invention relates to compounds and methods useful as inhibitors of phosphodiesterase 4 (PDE4) for the treatment or prevention of disease.

  本发明涉及化合物和方法，用于作为磷酸二酯酶4（PDE4）的抑制剂，用于治疗或预防疾病。
• [EN] HETEROARYL INHIBITORS OF PDE4<br/>[FR] INHIBITEURS HÉTÉROARYLE DE PDE4
  申请人：TETRA DISCOVERY PARTNERS LLC

  公开号：WO2014066659A9

  公开（公告）日：2015-03-05
• US9221843B2
  申请人：——

  公开号：US9221843B2

  公开（公告）日：2015-12-29