(R)-7-ethyl-8-isopropyl-5-methyl-2-(2-phenyl-1H-imidazol-1-yl)-7,8-dihydropteridin-6(5H)-one | 1313518-61-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: (R)-7-ethyl-8-isopropyl-5-methyl-2-(2-phenyl-1H-imidazol-1-yl)-7,8-dihydropteridin-6(5H)-one
• 英文别名: (7R)-7-ethyl-5-methyl-2-(2-phenylimidazol-1-yl)-8-propan-2-yl-7H-pteridin-6-one
• CAS: 1313518-61-4
• 化学式: C₂₁H₂₄N₆O
• 分子量: 376.461
• InChiKey: GNFVJCMQLYMYRH-MRXNPFEDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  28
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  67.2
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  磷酸三甲酯 在 potassium carbonate 作用下， 以 1,4-二氧六环 为溶剂， 反应 18.0h， 生成 (R)-7-ethyl-8-isopropyl-5-methyl-2-(2-phenyl-1H-imidazol-1-yl)-7,8-dihydropteridin-6(5H)-one
  参考文献：
  名称：

  Design and synthesis of highly selective, orally active Polo-like kinase-2 (Plk-2) inhibitors

  摘要：

  Polo-like kinase-2 (Plk-2) is a potential therapeutic target for Parkinson's disease and this Letter describes the SAR of a series of dihydropteridinone based Plk-2 inhibitors. By optimizing both the N-8 substituent and the biaryl region of the inhibitors we obtained single digit nanomolar compounds such as 37 with excellent selectivity for Plk-2 over Plk-1. When dosed orally in rats, compound 37 demonstrated a 41-45% reduction of pS129-alpha-synuclein levels in the cerebral cortex. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.02.065

文献信息

• [EN] PTERIDINONES AS INHIBITORS OF POLO - LIKE KINASE<br/>[FR] PTÉRIDINONES EN TANT QU'INHIBITEURS DE POLO-LIKE KINASE
  申请人：ELAN PHARM INC

  公开号：WO2011079114A1

  公开（公告）日：2011-06-30

  The present invention provides compounds having a structure according to Formula (I) or a salt or solvate thereof, wherein ring A, X, R1, R2, R3, R4, R5 and R6, are defined herein. The invention further provides pharmaceutical compositions including the compounds of the invention and methods of making and using the compounds and compositions of the invention, e.g., in the treatment and prevention of various disorders, such as Parkinson's disease.

  本发明提供了具有如下结构式(I)的化合物或其盐或溶剂化物，其中环A、X、R1、R2、R3、R4、R5和R6的定义如本文所述。本发明还提供了包括本发明化合物的药物组合物以及制造和使用本发明化合物和组合物的方法，例如，在治疗和预防各种疾病，如帕金森病。
• Selective and Brain-Permeable Polo-like Kinase-2 (Plk-2) Inhibitors That Reduce α-Synuclein Phosphorylation in Rat Brain
  作者：Danielle L. Aubele、Roy K. Hom、Marc Adler、Robert A. Galemmo、Simeon Bowers、Anh P. Truong、Hu Pan、Paul Beroza、R. Jeffrey Neitz、Nanhua Yao、May Lin、George Tonn、Heather Zhang、Michael P. Bova、Zhao Ren、Danny Tam、Lany Ruslim、Jeanne Baker、Linnea Diep、Kent Fitzgerald、Jennifer Hoffman、Ruth Motter、Donald Fauss、Pearl Tanaka、Michael Dappen、Jacek Jagodzinski、Wayman Chan、Andrei W. Konradi、Lee Latimer、Yong L. Zhu、Hing L. Sham、John P. Anderson、Marcelle Bergeron、Dean R. Artis

  DOI：10.1002/cmdc.201300166

  日期：2013.8

  involved in the phosphorylation of α‐synuclein in Lewy bodies, which are one of the hallmarks of Parkinson’s disease neuropathology. Potent, selective, brain‐penetrant inhibitors of Plk‐2 were obtained from a structure‐guided drug discovery approach driven by the first reported Plk‐2–inhibitor complexes. The best of these compounds showed excellent isoform and kinome‐wide selectivity, with physicochemical

  Polo-like kinase-2（Plk-2）被认为是路易体中α-突触核蛋白磷酸化的主要激酶，这是帕金森氏病神经病理学的标志之一。有效的，选择性的，脑渗透性的Plk-2抑制剂是从第一个报道的Plk-2抑制剂复合物驱动的结构指导药物发现方法获得的。这些化合物中最好的化合物表现出出色的同工型和全基因组选择性，其理化特性足以证实体内Plk-2抑制作用。一种这样的化合物在口服后可显着降低大鼠脑内α-突触核蛋白的磷酸化，并为该治疗途径对帕金森氏病的潜在治疗的未来研究提供了有用的探针。
• INHIBITORS OF POLO-LIKE KINASE
  申请人：Galemmo Robert A.

  公开号：US20110207716A1

  公开（公告）日：2011-08-25

  The present invention provides compounds having a structure according to Formula (I): or a salt or solvate thereof, wherein ring A, E 1 , E 2 , R 1 , R 2 , R 3 and R 4 are defined herein. The invention further provides pharmaceutical compositions including the compounds of the invention and methods of making and using the compounds and compositions of the invention, e.g., in the treatment and prevention of various disorders, such as Parkinson's disease.

  本发明提供了具有以下结构的化合物（I）的盐或溶剂，其中环A、E1、E2、R1、R2、R3和R4在此定义。本发明还提供了包括本发明化合物的制药组合物以及使用本发明化合物和组合物的方法，例如在治疗和预防各种疾病，如帕金森病方面的应用。
• Inhibitors of polo-like kinase
  申请人：Galemmo Robert A.

  公开号：US08445503B2

  公开（公告）日：2013-05-21

  The present invention provides compounds having a structure according to Formula (I): or a salt or solvate thereof, wherein ring A, X, R1, R2, R3, R4, R5 and R6 are defined herein. The invention further provides pharmaceutical compositions including the compounds of the invention and methods of making and using the compounds and compositions of the invention, e.g., in the treatment and prevention of various disorders, such as Parkinson's disease.

  本发明提供具有以下式子（I）结构的化合物或其盐或溶剂化物，其中环A、X、R1、R2、R3、R4、R5和R6在此定义。本发明还提供包括本发明化合物的制药组合物以及制备和使用本发明化合物和组合物的方法，例如在治疗和预防各种疾病，如帕金森病中的应用。
• PTERIDINONES AS INHIBITORS OF POLO-LIKE KINASE
  申请人：Elan Pharmaceuticals Inc.

  公开号：EP2516441B1

  公开（公告）日：2015-01-21