(7R)-7-ethyl-5-methyl-8-[(3S)-oxolan-3-yl]-2-[5-(1,3-thiazol-2-yl)-1H-pyrazol-4-yl]-7H-pteridin-6-one | 1431659-53-8

• 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: (7R)-7-ethyl-5-methyl-8-[(3S)-oxolan-3-yl]-2-[5-(1,3-thiazol-2-yl)-1H-pyrazol-4-yl]-7H-pteridin-6-one
• CAS: 1431659-53-8
• 化学式: C₁₉H₂₁N₇O₂S
• 分子量: 411.487
• InChiKey: PBCXNVUBDXBJNG-WCQYABFASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  29
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  128
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  3-(thiazol-2-yl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-4-ylboronic acid 、 在 四(三苯基膦)钯 、 sodium carbonate 作用下， 以 1,4-二氧六环 、 甲醇 、 乙二醇二甲醚 、 水 为溶剂， 反应 18.0h， 生成 (7R)-7-ethyl-5-methyl-8-[(3S)-oxolan-3-yl]-2-[5-(1,3-thiazol-2-yl)-1H-pyrazol-4-yl]-7H-pteridin-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

• 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.