3-Methyl-8-[(Piperidin-4-Yl)amino]-1,2-Dihydro-1,7-Naphthyridin-2-One

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: 3-Methyl-8-[(Piperidin-4-Yl)amino]-1,2-Dihydro-1,7-Naphthyridin-2-One
• 英文别名: 3-methyl-8-(piperidin-4-ylamino)-1H-1,7-naphthyridin-2-one
• 化学式: C₁₄H₁₈N₄O
• 分子量: 258.323
• InChiKey: WPUMQOWFWIAZCU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  66
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  (2-氯吡啶-3-基)氨基甲酸叔丁酯 在 盐酸 、 正丁基锂 、 四甲基乙二胺 、 sodium hydride 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 正己烷 、 N,N-二甲基甲酰胺 、 甲苯 、 mineral oil 为溶剂， 反应 118.83h， 生成 3-Methyl-8-[(Piperidin-4-Yl)amino]-1,2-Dihydro-1,7-Naphthyridin-2-One
  参考文献：
  名称：

  Fragment-Based Discovery of Low-Micromolar ATAD2 Bromodomain Inhibitors

  摘要：

  Overexpression of ATAD2 (ATPase family, AAA domain containing 2) has been linked to disease severity and progression in a wide range of cancers, and is implicated in the regulation of several drivers of cancer growth. Little is known of the dependence of these effects upon the ATAD2 bromodomain, which has been categorized as among the least tractable of its class. The absence of any potent, selective inhibitors limits clear understanding of the therapeutic potential of the bromodomain. Here, we describe the discovery of a hit from a fragment-based targeted array. Optimization of this produced the first known micromolar inhibitors of the ATAD2 bromodomain.

  DOI：

  10.1021/acs.jmedchem.5b00772

文献信息

• Fragment-Based Discovery of Low-Micromolar ATAD2 Bromodomain Inhibitors
  作者：Emmanuel H. Demont、Chun-wa Chung、Rebecca C. Furze、Paola Grandi、Anne-Marie Michon、Chris Wellaway、Nathalie Barrett、Angela M. Bridges、Peter D. Craggs、Hawa Diallo、David P. Dixon、Clement Douault、Amanda J. Emmons、Emma J. Jones、Bhumika V. Karamshi、Kelly Locke、Darren J. Mitchell、Bernadette H. Mouzon、Rab K. Prinjha、Andy D. Roberts、Robert J. Sheppard、Robert J. Watson、Paul Bamborough

  DOI：10.1021/acs.jmedchem.5b00772

  日期：2015.7.23

  Overexpression of ATAD2 (ATPase family, AAA domain containing 2) has been linked to disease severity and progression in a wide range of cancers, and is implicated in the regulation of several drivers of cancer growth. Little is known of the dependence of these effects upon the ATAD2 bromodomain, which has been categorized as among the least tractable of its class. The absence of any potent, selective inhibitors limits clear understanding of the therapeutic potential of the bromodomain. Here, we describe the discovery of a hit from a fragment-based targeted array. Optimization of this produced the first known micromolar inhibitors of the ATAD2 bromodomain.