(4-(5-chloro-4-(methylamino)pyrimidin-2-ylamino)phenyl)(morpholino)methanone | 1379676-36-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 恶嗪烷类
• 英文名称: (4-(5-chloro-4-(methylamino)pyrimidin-2-ylamino)phenyl)(morpholino)methanone
• 英文别名: [4-[[5-Chloro-4-(methylamino)pyrimidin-2-yl]amino]phenyl]-morpholin-4-ylmethanone；[4-[[5-chloro-4-(methylamino)pyrimidin-2-yl]amino]phenyl]-morpholin-4-ylmethanone
• CAS: 1379676-36-4
• 化学式: C₁₆H₁₈ClN₅O₂
• 分子量: 347.804
• InChiKey: AMQCBROKDRYSQO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  24
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  79.4
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  对氨基苯甲酸 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 甲乙醚 、 N,N-二甲基甲酰胺 为溶剂， 反应 36.0h， 生成 (4-(5-chloro-4-(methylamino)pyrimidin-2-ylamino)phenyl)(morpholino)methanone
  参考文献：
  名称：

  Discovery of Selective LRRK2 Inhibitors Guided by Computational Analysis and Molecular Modeling

  摘要：

  Mutations in the genetic sequence of leucine-rich repeat kinase 2 (LRRK2) have been linked to increased LRRK2 activity and risk for the development of Parkinson's disease (PD). Potent, and selective small molecules capable of inhibiting the kinase activity of LARK2 will be important tools for establishing a link between the kinase activity of LRRK2 and PD. In the absence of LRRK2 kinase domain crystal structures, a LRRK2 homology model was developed that provided robust guidance in the hit-to-lead optimization of small molecule LRRK2 inhibitors. Through a combination of molecular modeling, sequence analysis, and matched molecular pair (MMP) activity cliff analysis, a potent and selective lead inhibitor was discovered. The selectivity of this compound could be understood using the LRRK2 homology model, and application of this learning to a series of 2,4-diaminopyrimidine inhibitors in a scaffold hopping exercise led to the identification of highly potent and selective LRRK2 inhibitors that were also brain penetrable.

  DOI：

  10.1021/jm300452p

文献信息

• Compositions and methods for treating Dengue virus infection
  申请人：The J. David Gladstone Institutes

  公开号：US10004751B2

  公开（公告）日：2018-06-26

  The present disclosure provides methods of treating a flavivirus infection, and compositions for use in the methods.

  本公开提供了治疗黄病毒感染的方法以及用于这些方法的组合物。
• COMPOSITIONS AND METHODS FOR TREATING DENGUE VIRUS INFECTION
  申请人：The J. David Gladstone Institutes

  公开号：EP3166637B1

  公开（公告）日：2020-01-29
• [EN] COMPOSITIONS AND METHODS FOR TREATING DENGUE VIRUS INFECTION<br/>[FR] COMPOSITIONS ET MÉTHODES POUR LE TRAITEMENT D'UNE INFECTION PAR LE VIRUS DE LA DENGUE
  申请人：DAVID GLADSTONE INST

  公开号：WO2016007540A2

  公开（公告）日：2016-01-14

  The present disclosure provides methods of treating a flavivirus infection, and compositions for use in the methods.
• Discovery of Selective LRRK2 Inhibitors Guided by Computational Analysis and Molecular Modeling
  作者：Huifen Chen、Bryan K. Chan、Jason Drummond、Anthony A. Estrada、Janet Gunzner-Toste、Xingrong Liu、Yichin Liu、John Moffat、Daniel Shore、Zachary K. Sweeney、Thuy Tran、Shumei Wang、Guiling Zhao、Haitao Zhu、Daniel J. Burdick

  DOI：10.1021/jm300452p

  日期：2012.6.14

  Mutations in the genetic sequence of leucine-rich repeat kinase 2 (LRRK2) have been linked to increased LRRK2 activity and risk for the development of Parkinson's disease (PD). Potent, and selective small molecules capable of inhibiting the kinase activity of LARK2 will be important tools for establishing a link between the kinase activity of LRRK2 and PD. In the absence of LRRK2 kinase domain crystal structures, a LRRK2 homology model was developed that provided robust guidance in the hit-to-lead optimization of small molecule LRRK2 inhibitors. Through a combination of molecular modeling, sequence analysis, and matched molecular pair (MMP) activity cliff analysis, a potent and selective lead inhibitor was discovered. The selectivity of this compound could be understood using the LRRK2 homology model, and application of this learning to a series of 2,4-diaminopyrimidine inhibitors in a scaffold hopping exercise led to the identification of highly potent and selective LRRK2 inhibitors that were also brain penetrable.