2-(4-chlorophenyl)-2,3-dihydropyrido[2,3-d]pyrimidin-4(1H)-one | 31911-86-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶并嘧啶类
• 英文名称: 2-(4-chlorophenyl)-2,3-dihydropyrido[2,3-d]pyrimidin-4(1H)-one
• 英文别名: 2-(4-chlorophenyl)-2,3-dihydro-1H-pyrido[2,3-d]pyrimidin-4-one
• CAS: 31911-86-1
• 化学式: C₁₃H₁₀ClN₃O
• 分子量: 259.695
• InChiKey: JBJHRALZMBCUCU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  18
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  54
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  2-氨基-3-氰基吡啶 、 4-氯苯甲醛 在 水 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 反应 0.08h， 以90%的产率得到2-(4-chlorophenyl)-2,3-dihydropyrido[2,3-d]pyrimidin-4(1H)-one
  参考文献：
  名称：

  DBU在水性介质中催化微波辅助合成2,3-二氢吡啶并[2,3- d ]嘧啶-4（1 H）-一

  摘要：

  一种清洁的绿色，高效且简便的协议被用来合成一系列2,3-二氢吡啶并[2,3- d ]嘧啶4（1 H）-酮。水微波辐射下，DBU催化2-氨基烟腈与羰基的反应，收率高。DBU–H 2 O系统可以循环使用五次，而不会造成活动损失。

  DOI：

  10.1039/c2gc16469h

文献信息

• Microwave-assisted synthesis of 2,3-dihydropyrido[2,3-d]pyrimidin-4(1H)-ones catalyzed by DBU in aqueous medium
  作者：Liupan Yang、Daxin Shi、Shu Chen、Hongxin Chai、Danfei Huang、Qi Zhang、Jiarong Li

  DOI：10.1039/c2gc16469h

  日期：——

  A clean green, efficient and facile protocol was developed for the synthesis of a series of 2,3-dihydropyrido[2,3-d]pyrimidin-4(1H)-ones in water with good yield by the reaction of 2-amino-nicotinonitriles with carbonyls catalyzed by DBU under microwave irradiation. The DBU–H2O system can be recycled five times without activity loss.

  一种清洁的绿色，高效且简便的协议被用来合成一系列2,3-二氢吡啶并[2,3- d ]嘧啶4（1 H）-酮。水微波辐射下，DBU催化2-氨基烟腈与羰基的反应，收率高。DBU–H 2 O系统可以循环使用五次，而不会造成活动损失。
• Discovery of potent and selective nonplanar tankyrase inhibiting nicotinamide mimics
  作者：Yves Nkizinkiko、B.V.S. Suneel Kumar、Variam Ullas Jeankumar、Teemu Haikarainen、Jarkko Koivunen、Chanduri Madhuri、Perumal Yogeeswari、Harikanth Venkannagari、Ezeogo Obaji、Taina Pihlajaniemi、Dharmarajan Sriram、Lari Lehtiö

  DOI：10.1016/j.bmc.2015.06.063

  日期：2015.8

  Diphtheria toxin-like ADP-ribosyltransferases catalyse a posttranslational modification, ADP-ribosylation and form a protein family of 17 members in humans. Two of the family members, tankyrases 1 and 2, are involved in several cellular processes including mitosis and Wnt/beta-catenin signalling pathway. They are often over-expressed in cancer cells and have been linked with the survival of cancer cells making them potential therapeutic targets. In this study, we identified nine tankyrase inhibitors through virtual and in vitro screening. Crystal structures of tankyrase 2 with the compounds showed that they bind to the nicotinamide binding site of the catalytic domain. Based on the co-crystal structures we designed and synthesized a series of tetrahydroquinazolin-4-one and pyridopyrimidin-4-one analogs and were subsequently able to improve the potency of a hit compound almost 100-fold (from 11 mu M to 150 nM). The most potent compounds were selective towards tankyrases over a panel of other human ARTD enzymes. They also inhibited Wnt/beta-catenin pathway in a cell-based reporter assay demonstrating the potential usefulness of the identified new scaffolds for further development. (C) 2015 Elsevier Ltd. All rights reserved.