5AL2 | 79973-92-5

• 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: 5AL2
• 英文别名: 2-(4-propan-2-ylphenyl)-2,3-dihydro-1H-pyrido[2,3-d]pyrimidin-4-one
• CAS: 79973-92-5
• 化学式: C₁₆H₁₇N₃O
• 分子量: 267.33
• InChiKey: UWKUUJNROWNYPA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.25
• 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-氨基烟酸乙酯 在 氨 、 zinc(II) chloride 作用下， 反应 120.2h， 生成 5AL2
  参考文献：
  名称：

  1,2-二氢-2-（3-吡啶基）-3H-吡啶并[2,3-d]嘧啶-4-酮及其相关化合物的合成及利尿活性。

  摘要：

  DOI：

  10.1021/jm00343a022

文献信息

• 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.
• PARISH, H. A. ,, JR;GILLIOM, R. D.;PURCELL, W. P.;BROWNE, R. K.;SPIRK, R.+, J. MED. CHEM., 1982, 25, N 1, 98-102
  作者：PARISH, H. A. ,, JR、GILLIOM, R. D.、PURCELL, W. P.、BROWNE, R. K.、SPIRK, R.+

  DOI：——

  日期：——
• Syntheses and diuretic activity of 1,2-dihydro-2-(3-pyridyl)-3H-pyrido[2,3-d]pyrimidin-4-one and related compounds
  作者：Harlie A. Parish、Richard D. Gilliom、William P. Purcell、Ronald K. Browne、Roy F. Spirk、Harold D. White

  DOI：10.1021/jm00343a022

  日期：1982.1