2-Chloro-7-(2,2,2-trifluoroethyl)-8-(3,3,3-trifluoropropyl)-5,7-dihydropteridin-6-one | 1313520-38-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 蝶啶及其衍生物
• 英文名称: 2-Chloro-7-(2,2,2-trifluoroethyl)-8-(3,3,3-trifluoropropyl)-5,7-dihydropteridin-6-one
• 英文别名: 2-chloro-7-(2,2,2-trifluoroethyl)-8-(3,3,3-trifluoropropyl)-5,7-dihydropteridin-6-one
• CAS: 1313520-38-5
• 化学式: C₁₁H₉ClF₆N₄O
• 分子量: 362.662
• InChiKey: NRZILZSJMNGSER-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  23
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  58.1
• 氢给体数：
  1
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  磷酸三甲酯 、 2-Chloro-7-(2,2,2-trifluoroethyl)-8-(3,3,3-trifluoropropyl)-5,7-dihydropteridin-6-one 在 potassium carbonate 作用下， 以 1,4-二氧六环 为溶剂， 反应 18.0h， 生成 2-chloro-5-methyl-7-(2,2,2-trifluoroethyl)-8-(3,3,3-trifluoropropyl)-7,8-dihydropteridine-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
• 作为产物：
  描述：

  Methyl 4,4,4-trifluoro-2-(3,3,3-trifluoropropylamino)butanoate 在 铁粉 、 碳酸氢钠 作用下， 以 乙醚 、 正己烷 为溶剂， 反应 20.0h， 生成 2-Chloro-7-(2,2,2-trifluoroethyl)-8-(3,3,3-trifluoropropyl)-5,7-dihydropteridin-6-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

• 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。
• US8541418B2
  申请人：——

  公开号：US8541418B2

  公开（公告）日：2013-09-24
• [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：WO2011079118A1

  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, E1, E2, R1, R2, R3 and R4 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.
• [EN] INHIBITORS OF POLO-LIKE KINASE<br/>[FR] INHIBITEURS DE KINASE DE TYPE POLO
  申请人：ELAN PHARM INC

  公开号：WO2012048129A2

  公开（公告）日：2012-04-12

  The present invention provides compounds having a structure according to Formula (I):or a salt or solvate thereof, wherein ring A, U1, U2, U3, R2, R3 and R4 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.
• Design and synthesis of highly selective, orally active Polo-like kinase-2 (Plk-2) inhibitors
  作者：Simeon Bowers、Anh P. Truong、Michael Ye、Danielle L. Aubele、Jennifer M. Sealy、R. Jeffrey Neitz、Roy K. Hom、Wayman Chan、Michael S. Dappen、Robert A. Galemmo、Andrei W. Konradi、Hing L. Sham、Yong L. Zhu、Paul Beroza、George Tonn、Heather Zhang、Jennifer Hoffman、Ruth Motter、Donald Fauss、Pearl Tanaka、Michael P. Bova、Zhao Ren、Danny Tam、Lany Ruslim、Jeanne Baker、Deepal Pandya、Linnea Diep、Kent Fitzgerald、Dean R. Artis、John P. Anderson、Marcelle Bergeron

  DOI：10.1016/j.bmcl.2013.02.065

  日期：2013.5

  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.