methyl (2R)-2-[(2-chloro-5-nitropyrimidin-4-yl)-(3,3-difluorocyclobutyl)amino]butanoate | 1446420-20-7

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: methyl (2R)-2-[(2-chloro-5-nitropyrimidin-4-yl)-(3,3-difluorocyclobutyl)amino]butanoate
• CAS: 1446420-20-7
• 化学式: C₁₃H₁₅ClF₂N₄O₄
• 分子量: 364.736
• InChiKey: PHYICXHXIGKKJW-MRVPVSSYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  24
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  101
• 氢给体数：
  0
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  methyl (2R)-2-[(2-chloro-5-nitropyrimidin-4-yl)-(3,3-difluorocyclobutyl)amino]butanoate 、 溶剂黄146 在 铁粉 作用下， 反应 2.0h， 生成 (7R)-2-chloro-8-(3,3-difluorocyclobutyl)-7-ethyl-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
• 作为产物：
  描述：

  methyl (R)-2-aminobutanoate 在 sodium acetate 、 三乙酰氧基硼氢化钠 、 碳酸氢钠 作用下， 以 乙醚 、 正己烷 、 二氯甲烷 为溶剂， 反应 36.0h， 生成 methyl (2R)-2-[(2-chloro-5-nitropyrimidin-4-yl)-(3,3-difluorocyclobutyl)amino]butanoate
  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.