tert-butyl (trans-4-((6-(3-formylphenyl)pyrazin-2-yl)amino)cyclohexyl)carbamate | 1258858-98-8

• 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: tert-butyl (trans-4-((6-(3-formylphenyl)pyrazin-2-yl)amino)cyclohexyl)carbamate
• 英文别名: tert-butyl N-[4-[[6-(3-formylphenyl)pyrazin-2-yl]amino]cyclohexyl]carbamate
• CAS: 1258858-98-8
• 化学式: C₂₂H₂₈N₄O₃
• 分子量: 396.489
• InChiKey: IEYOIKNGKQIOAJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  29
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  93.2
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2,4-噻唑烷二酮 、 tert-butyl (trans-4-((6-(3-formylphenyl)pyrazin-2-yl)amino)cyclohexyl)carbamate 在 哌啶 作用下， 以 叔丁醇 为溶剂， 以63%的产率得到tert-butyl (trans-4-((6-(3-((Z)-(2,4-dioxothiazolidin-5-ylidene)methyl)phenyl)pyrazin-2-yl)amino)cyclohexyl)carbamate
  参考文献：
  名称：

  Implications of Promiscuous Pim-1 Kinase Fragment Inhibitor Hydrophobic Interactions for Fragment-Based Drug Design

  摘要：

  We have studied the subtleties of fragment docking and binding using data generated in a Pim-1 kinase inhibitor program. Crystallographic and docking data analyses have been undertaken using inhibitor complexes derived from an in-house surface plasmon resonance (SPR) fragment screen, a virtual needle screen, and a de novo designed fragment inhibitor hybrid. These investigations highlight that fragments that do not fill their binding pocket can exhibit promiscuous hydrophobic interactions due to the lack of steric constraints imposed on them by the boundaries of said pocket. As a result, docking modes that disagree with an observed crystal structure but maintain key crystallographically observed hydrogen bonds still have potential value in ligand design and optimization. This observation runs counter to the lore in fragment-based drug design that all fragment elaboration must be based on the parent crystal structure alone.

  DOI：

  10.1021/jm2014698
• 作为产物：
  描述：

  1,4-环己烷二胺 在 bis-triphenylphosphine-palladium(II) chloride 、 potassium carbonate 、 N,N-二异丙基乙胺 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 33.5h， 生成 tert-butyl (trans-4-((6-(3-formylphenyl)pyrazin-2-yl)amino)cyclohexyl)carbamate
  参考文献：
  名称：

  Implications of Promiscuous Pim-1 Kinase Fragment Inhibitor Hydrophobic Interactions for Fragment-Based Drug Design

  摘要：

  We have studied the subtleties of fragment docking and binding using data generated in a Pim-1 kinase inhibitor program. Crystallographic and docking data analyses have been undertaken using inhibitor complexes derived from an in-house surface plasmon resonance (SPR) fragment screen, a virtual needle screen, and a de novo designed fragment inhibitor hybrid. These investigations highlight that fragments that do not fill their binding pocket can exhibit promiscuous hydrophobic interactions due to the lack of steric constraints imposed on them by the boundaries of said pocket. As a result, docking modes that disagree with an observed crystal structure but maintain key crystallographically observed hydrogen bonds still have potential value in ligand design and optimization. This observation runs counter to the lore in fragment-based drug design that all fragment elaboration must be based on the parent crystal structure alone.

  DOI：

  10.1021/jm2014698

文献信息

• RHODANINES AND RELATED HETEROCYCLES AS KINASE INHIBITORS
  申请人：HADDACH Mustapha

  公开号：US20100331315A1

  公开（公告）日：2010-12-30

  The invention provides compounds that inhibit PIM kinases and/or CK2, and compositions containing such compounds. These compounds and compositions are useful for treating proliferative disorders such as cancer, as well as other kinase-associated conditions including inflammation, pain, vascular disorders, pathogenic infections and certain immunological disorders.

  该发明提供了能够抑制PIM激酶和/或CK2的化合物以及含有这些化合物的组合物。这些化合物和组合物可用于治疗增殖性疾病如癌症，以及其他与激酶相关的疾病，包括炎症、疼痛、血管疾病、病原体感染和某些免疫性疾病。
• [EN] RHODANINES AND RELATED HETEROCYCLES AS KINASE INHIBITORS<br/>[FR] RHODANINES ET HÉTÉROCYCLES ASSOCIÉS EN TANT QU'INHIBITEURS DE KINASE
  申请人：CYLENE PHARMACEUTICALS INC

  公开号：WO2010148351A1

  公开（公告）日：2010-12-23

  The invention provides compounds that inhibit PIM kinases and/or CK2, and compositions containing such compounds. These compounds and compositions are useful for treating proliferative disorders such as cancer, as well as other kinase-associated conditions including inflammation, pain, vascular disorders, pathogenic infections and certain immunological disorders.
• Implications of Promiscuous Pim-1 Kinase Fragment Inhibitor Hydrophobic Interactions for Fragment-Based Drug Design
  作者：Andrew C. Good、Jinyu Liu、Bradford Hirth、Gary Asmussen、Yibin Xiang、Hans-Peter Biemann、Kimberly A. Bishop、Trisha Fremgen、Maria Fitzgerald、Tatiana Gladysheva、Annuradha Jain、Katherine Jancsics、Markus Metz、Andrew Papoulis、Renato Skerlj、J. David Stepp、Ronnie R. Wei

  DOI：10.1021/jm2014698

  日期：2012.3.22

  We have studied the subtleties of fragment docking and binding using data generated in a Pim-1 kinase inhibitor program. Crystallographic and docking data analyses have been undertaken using inhibitor complexes derived from an in-house surface plasmon resonance (SPR) fragment screen, a virtual needle screen, and a de novo designed fragment inhibitor hybrid. These investigations highlight that fragments that do not fill their binding pocket can exhibit promiscuous hydrophobic interactions due to the lack of steric constraints imposed on them by the boundaries of said pocket. As a result, docking modes that disagree with an observed crystal structure but maintain key crystallographically observed hydrogen bonds still have potential value in ligand design and optimization. This observation runs counter to the lore in fragment-based drug design that all fragment elaboration must be based on the parent crystal structure alone.